MB Notes

Notes

Introduction

2 one in four American women: Medco Health Solutions, “America’s State of Mind Report,” November 2011.

4 By 2006 the antidepressant Zoloft: Charles Barber, Comfortably Numb: How Psychiatry Is Medicating a Nation (New York: Random House, 2009).

4 The latest news is particularly: IMS National Prescription Audit, IMS Health 2013 (accessed at http://www.medscape.com/viewarticle/820011).

4 Prescribing antipsychotics: Daniel E. Casey, “Tardive Dyskinesia and Atypical Antipsychotic Drugs,” Schizophrenia Research 35 (1999): S61–S66; Wildon R. Farwell et al., “Weight Gain and New Onset Diabetes Associated with Olanzapine and Risperidone,” Journal of General Internal Medicine 19, no. 12 (2004): 1200–1205; Robert L. Dufresne, “Weighing In: Emergent Diabetes Mellitus and Second-Generation Antipsychotics,” Annals of Pharmacotherapy 41, no. 10 (2007): 1725–27.

5 we take 50 percent: IMS Institute, “Medicine Use and Shifting Costs of Healthcare: A Review of the Use of Medicines in the U.S. in 2013,” April 2014.

5 Four out of five prescriptions: Ramin Mojtabai, “Clinician-Identified Depression in Community Settings: Concordance with Structured-Interview Diagnoses,” Psychotherapy and Psychosomatics 82, no. 3 (2013): 161–69.

5 surveys of primary care doctors: Christopher M. Callahan and German Elias Berrios, Reinventing ­Depression: A History of the Treatment of Depression in Primary Care, 1940–2004 (USA: Oxford University Press, 2005).

Chapter One: Own Your Moods

14 By evolutionary design: J. O. Wolff and J. A. Peterson, “An Offspring-Defense Hypothesis for Territoriality in Female Mammals,” Ethology Ecology & Evolution 10, no. 3 (1998): 227–39; Shelley E. Taylor, The Tending Instinct: Women, Men, and the Biology of Relationships (New York: Macmillan, 2003).

15 Drug makers had found: Jim Rosack, “Drug Makers Find Sept. 11 a Marketing Opportunity,” Psychiatric News, March 11, 2002.

15 Glaxo doubled its advertising: Charles Barber, Comfortably Numb.

16 As the New York Times explained: Amy Harmon, “Young, Assured and Playing Pharmacist to Friends,” New York Times 16 (2005).

16 Numerous medical chart: World Health Organization, Department of Mental Health and Substance Dependence, Gender Disparities in Mental Health, 2002.

17 People who don’t really need these meds: Substance Abuse and Mental Health Services Administration, Results from the 2012 National Survey on Drug Use and Health: Mental Health Findings, NSDUH Series H-47, HHS Publication No. (SMA) 13-4805, 2013.

18 it’s more complicated: Many concepts in this book have been simplified. There are three types of estrogen in the body (17-beta estradiol, estrone, and estriol), yet I use the word estrogen throughout this book. I may talk about low levels of this or that hormone or neurotransmitter, but one molecule does not completely cause a behavior. Nothing happens in a vacuum in the human body, and every shift in one chemical is liable to set off a cascade of events in others. Small events can trigger larger countermeasures as the body and brain struggle to reach a new balance, or homeostasis. The brain adapts to new conditions as receptors upregulate or downregulate in response to the low or high functioning of a specific neurotransmitter. Also, nothing is one-size-fits-all because everyone’s genes are different; individuals process drugs in idiosyncratic ways thanks to genetic variability, and many are more susceptible to psychiatric complaints because of their genetic predispositions.

18 When serotonin levels are lower: Khaled M. K. Ismail and P. M. S. O’Brien, “Premenstrual Syndrome,” Current Obstetrics & Gynecology 11, no. 4 (2001): 251–55.

19 Patients report having less: W. J. Barnhart et al., “SSRI-Induced Apathy Syndrome: A Clinical Review,” Journal of Psychiatric Practice 10 (2004): 196–99; R. Hoehn-Saric et al., “Apathy and Indifference in ­Patients on Fluvoxamine and Fluoxetine,” Journal of Clinical Psychopharmacology 10 (1990): 343–46.

19 Women’s brains develop differently: Louann Brizendine, The Female Brain (New York: Random House, 2007); Helen Fisher, Why We Love: The Nature and Chemistry of Romantic Love (New York: Macmillan, 2004).

20 Even more brain changes occur: Ibid.

20 Our memory center: Fisher, Why We Love.

20 The hippocampus can calm: Cora Hübner et al., “Ex Vivo Dissection of Optogenetically Activated mPFC and Hippocampal Inputs to Neurons in the Basolateral Amygdala: Implications for Fear and Emotional Memory,” Frontiers in Behavioral Neuroscience 8, no. 64 (2014).

20 are larger in men: Jill M. Goldstein et al., “Normal Sexual Dimorphism of the Adult Human Brain ­Assessed by in Vivo Magnetic Resonance Imaging,” Cerebral Cortex 11, no. 6 (2001): 490–97.

20 have receptors for testosterone: C. E. Roselli et al., “Quantitative Distribution of Nuclear Androgen ­Receptors in Microdissected Areas of the Rat Brain,” Neuroendocrinology 49, no. 5 (1989): 449–53.

20 When under acute stress: Benno Roozendaal et al., “Stress, Memory and the Amygdala,” Nature Reviews Neuroscience 10, no. 6 (2009): 423–33.

20 The biggest problems: Ajai Vyas et al., “Chronic Stress Induces Contrasting Patterns of Dendritic Remodeling in Hippocampal and Amygdaloid Neurons,” Journal of Neuroscience 22, no. 15 (2002): 6810–18.

20 It becomes atrophied: Scott L. Rauch et al., “Neurocircuitry Models of Posttraumatic Stress Disorder and Extinction: Human Neuroimaging Research—Past, Present, and Future,” Biological Psychiatry 60, no. 4 (2006): 376–82.

20 seen in anyone undergoing chronic stress: Bruce S. McEwen, “Plasticity of the Hippocampus: Adaptation to Chronic Stress and Allostatic Load,” Annals of the New York Academy of Sciences 933, no. 1 (2001): 265–77; Lisa Eiland and Bruce S. McEwen, “Early Life Stress Followed by Subsequent Adult Chronic Stress Potentiates Anxiety and Blunts Hippocampal Structural Remodeling,” Hippocampus 22, no. 1 (2012): 82–91.

20 Intuiting the motives and feelings: S. Baron-Cohen, The Essential Difference (New York: Basic Books, 2003).

21 The better we are at sensing: A. D. Craig, “Human Feelings: Why Are Some More Aware Than Others?” Trends in Cognitive Sciences 8, no. 6 (2004): 239–41; Beate M. Herbert et al., “Interoceptive Sensitivity and Emotion Processing: An EEG Study,” International Journal of Psychophysiology 65, no. 3 (2007): 214–27.

21 The insula: Tania Singer et al., “A Common Role of Insula in Feelings, Empathy and Uncertainty,” Trends in Cognitive Sciences 13, no. 8 (2009): 334–40.

21 is noticeably bigger: John S. Allen et al., “Sexual Dimorphism and Asymmetries in the Gray–White Composition of the Human Cerebrum,” Neuroimage 18, no. 4 (2003): 880–94.

21 The insula not only helps: Kirsten G. Volz and D. Yves Von Cramon, “What Neuroscience Can Tell About Intuitive Processes in the Context of Perceptual Discovery,” Journal of Cognitive Neuroscience 18, no. 12 (2006): 2077–87.

21 Women have more brain circuitry: Brizendine, The Female Brain.

21 Testosterone impairs empathy: Jack Van Honk et al., “Testosterone Administration Impairs Cognitive Empathy in Women Depending on Second-to-Fourth Digit Ratio,” Proceedings of the National Academy of Sciences (PNAS) 108, no. 8 (2011): 3448–52; S. Lutchmaya et al., “Fetal Testosterone and Eye Contact in 12-Month-Old Human Infants,” Infant Behavior & Development 25 (2002): 327–35; E. Chapman et al., “Fetal Testosterone and Empathy: Evidence from the Empathy Quotient (EQ) and the ‘Reading the Mind in the Eyes’ Test,” Social Neuroscience 1 (2006): 135–48; Simon Baron-Cohen and Sally Wheelwright, “The Empathy Quotient: An Investigation of Adults with Asperger Syndrome or High Functioning Autism, and Normal Sex Differences,” Journal of Autism and Developmental Disorders 34, no. 2 (2004): 163–75.

22 Oxytocin, the hormone: Jorge A. Barraza and Paul J. Zak, “Empathy Toward Strangers Triggers Oxytocin ­Release and Subsequent Generosity,” Annals of the New York Academy of Sciences 1167, no. 1 (2009): 182–89.

22 It also helps us: Carsten K. W. De Dreu et al., “The Neuropeptide Oxytocin Regulates Parochial Altruism in Intergroup Conflict Among Humans,” Science 328, no. 5984 (2010): 1408–11.

22 In hostile environments: Shelley E. Taylor, The Tending Instinct: Women, Men, and the Biology of Relationships (New York: Macmillan, 2003).

22 playing out as aggression: Shelley E. Taylor, “Tend and Befriend Biobehavioral Bases of Affiliation Under Stress,” Current Directions in Psychological Science 15, no. 6 (2006): 273–77.

22 Protective mothers’ maternal aggression: Beth L. Mah et al., “Oxytocin Promotes Protective Behavior in Depressed Mothers: A Pilot Study with the Enthusiastic Stranger Paradigm,” Depression and Anxiety (2014); Oliver J. Bosch, “Maternal Aggression in Rodents: Brain Oxytocin and Vasopressin Mediate Pup Defense,” Philosophical Transactions of the Royal Society B: Biological Sciences 368, no. 1631 (2013): 20130085.

22 Girls flock together: Brizendine, The Female Brain.

22 Estrogen triggers dopamine: Ibid.

22 Whereas women tend to discuss: Deborah Tannen, You Just Don’t Understand: Women and Men in Conversation (New York: HarperCollins, 2001).

22 The connections between the areas: Brizendine, The Female Brain.

22 Women also have more bilateral processing: Madhura Ingalhalikar et al., “Sex Differences in the Structural Connectome of the Human Brain,” Proceedings of The National Academy of Sciences 111, no. 2 (2014): 823–28; Theodore D. Satterthwaite et al., “Linked Sex Differences in Cognition and Functional Connectivity in Youth,” Cerebral Cortex (2014): bhu036.

23 better at multitasking: Gijsbert Stoet et al., “Are Women Better Than Men at Multi-Tasking?” BMC Psychology 1, no. 1 (2013): 18.

23 Men’s brains have more linkages: Ingalhalikar et al., “Sex Differences.”

23 Men tend to outperform women: Satterthwaite et al., “Linked Sex Differences,” bhu036.

23 outperform men on a “lost key”: Stoet et al., “Are Women Better Than Men,” 18.

24 In adulthood, women are twice as likely: R. C. Kessler et al., “Sex and Depression in the National Comorbidity Survey. I: Lifetime Prevalence, Chronicity and Recurrence,” Journal of Affective Disorders 29 (1993): 85–96; G. F. Placidi et al., “The Semi-Structured Affective Temperament Interview (TEMPS-I): Reliability and Psychometric Properties in 1010 14–26-Year-Old Students,” Journal of Affective Disorders 47, no. 1–3 (1998): 1–10; Jules Angst et al., “Gender Differences in Depression,” European Archives of Psychiatry and Clinical Neuroscience 252, no. 5 (2002): 201–9; C. Kuehner, “Gender Differences in Unipolar Depression: An Update of Epidemiological Findings and Possible Explanations,” Acta Psychiatrica Scandinavica 108 (2003): 163–74.

24 two to four times more likely: Robin W. Simon and Leda E. Nath, “Gender and Emotion in the United States: Do Men and Women Differ in Self-Reports of Feelings and Expressive Behavior?” American Journal of Sociology 109, no. 5 (2004): 1137–76; Richard Gater et al., “Sex Differences in the Prevalence and Detection of Depressive and Anxiety Disorders in General Health Care Settings: Report from the World Health Organization Collaborative Study on Psychological Problems in General Health Care,” Archives of General Psychiatry 55, no. 5 (1998): 405.

24 The increased risk: Marco Piccinelli and Greg Wilkinson, “Gender Differences in Depression: Critical Review,” British Journal of Psychiatry 177, no. 6 (2000): 486–92.

24 Although some of the increased incidence: Janet Shibley Hyde et al., “The ABCs of Depression: Integrating Affective, Biological, and Cognitive Models to Explain the Emergence of the Gender Difference in Depression,” Psychological Review 115, no. 2 (2008): 291.

24 mood changes caused by variations: E. W. Freeman et al., “Hormones and Menopausal Status as Predictors of Depression in Women in Transition to Menopause,” Archives of General Psychiatry 61 (2004): 62–70; Jennifer L. Payne et al., “A Reproductive Subtype of Depression: Conceptualizing Models and Moving Toward Etiology,” Harvard Review of Psychiatry 17, no. 2 (2009): 72–86.

24 specific sensitivity: P. J. Schmidt et al., “Differential Behavioral Effects of Gonadal Steroids in Women with and in Those without Premenstrual Syndrome,” New England Journal of Medicine 338 (1998): 209–16.

24 some lucky ones don’t, possibly dictated by genes: J. Guintivano et al., “Antenatal Prediction of Postpartum Depression with Blood DNA Methylation Biomarkers,” Molecular Psychiatry (2013): 1-8.

24 when your hormones aren’t fluctuating: Payne et al., “A Reproductive Subtype of Depression,” 72–86.

24 After menopause: P. Bebbington et al., “The Influence of Age and Sex on the Prevalence of Depressive Conditions: Report from the National Survey of Psychiatric Morbidity,” Psychological Medicine 15 (2003): 74–83.

24 especially two years after: Ellen W. Freeman et al., “Longitudinal Pattern of Depressive Symptoms Around Natural Menopause,” JAMA Psychiatry 71, no. 1 (2014): 36–43.

25 Progesterone is implicated: J. H. Gold et al., “Late Luteal Phase Dysphoric Disorder: Literature Review,” DSM-IV Sourcebook 2 (1996).

25 postpartum depression: Mohammed T. Abou-Saleh et al., “Hormonal Aspects of Postpartum Depression,” Psychoneuroendocrinology 23, no 5 (1998): 465–75.

25 dysthymia: C. Neill Epperson et al., “Gonadal Steroids in the Treatment of Mood Disorders,” Psychosomatic Medicine 61, no. 5 (1999): 676–97.

25 The increased incidences of depression: Barbara L. Parry, “Reproductive Factors Affecting the Course of Affective Illness in Women,” Psychiatric Clinics of North America 12, no. 1 (1989): 207–20.

25 If women develop these behaviors: Randolph M. Nesse, “Is Depression an Adaptation?” Archives of General Psychiatry 57, no. 1 (2000): 14–20.

25 When women feel under threat: J. E. Y. Wei et al., “Estrogen Protects Against the Detrimental Effects of Repeated Stress on Glutamatergic Transmission and Cognition,” Molecular Psychiatry (2013); R. E. Bowman et al., “Chronic Stress Effects on Memory: Sex Differences in Performance and Monoamines,” Hormones and Behavior 43 (2003): 48–59; R. E. Bowman, “Stress-Induced Changes in Spatial Memory Are Sexually Differentiated and Vary Across the Lifespan,” Journal of Neuroendocrinology 17 (2005): 526–35.

25 One of the ways estrogen builds resilience: David R. Rubinow et al., “Estrogen-Serotonin Interactions: Implications for Affective Regulation,” Biological Psychiatry 44, no. 9 (1998): 839–50; Hadine Joffe and Lee S. Cohen, “Estrogen, Serotonin, and Mood Disturbance: Where Is the Therapeutic Bridge?” Biological Psychiatry 44, no. 9 (1998): 798–811.

25 Serotonin activity is greater: I. Hindberg and O. Naesh,”Serotonin Concentrations in Plasma and Variations During the Menstrual Cycle,” Clinical Chemistry 38, no. 10 (1992): 2087–89.

25 When estrogen surges: C. L. Bethea et al., “Ovarian Steroids and Serotonin Neural Function,” Molecular Neurobiology 18, no. 2 (1998): 87–123.

25 causes serotonin receptors: Barbara E. H. Sumner et al., “Effects of Tamoxifen on Serotonin Transporter and 5-Hydroxytryptamine 2A Receptor Binding Sites and Mrna Levels in the Brain of Ovariectomized Rats with or without Acute Estradiol Replacement,” Molecular Brain Research 73, no. 1 (1999): 119–28. Zenab Amin et al., “Effect of Estrogen-Serotonin Interactions on Mood and Cognition,” Behavioral and Cognitive Neuroscience Reviews 4, no. 1 (2005): 43–58.

25 to be made: 5HT2A.

26 The natural process of stress: Ibid.; Rubinow et al.; Sumner et al., “Effects of Tamoxifen,” 119–28.

26 normalizes our: increased SERT production, the presynaptic reuptake inhibitor upon which SSRIs dock.

26 sexual side effects: There are gender differences in serotonin receptor numbers and sensitivity. Women have slightly different responses to the serotonin-enhancing drug MDMA (called Ecstasy or Molly) due to these receptor differences, for example. Researchers have shown sex differences in the serotonin transporter where the SSRIs dock, called SERT. If you have more SERT, you have more recycling of serotonin back into the pitching cell, so less is available for the catching cell. More SERT is the opposite of more antidepressants, which block the SERT site. The gene implicated in depression that helps to guide the manufacture of SERT, called SLC6A4, has a “switch” that is turned on by estrogen. Other subtypes of serotonin receptors have gender differences or estrogen responsiveness as well. The number of SERT docking sites decreases as depressed women age, but not depressed men. This may have to do with waning estrogen levels seen after menopause. Aging seems to affect women more than men when it comes to their serotonergic systems.

26 People on SSRIs report less: M. Oleshansky and L. Labbate, “Inability to Cry During SRI Treatment,” Journal of Clinical Psychiatry 57 (1996): 593; Jonathan Price et al., “Emotional Side-Effects of Selective Serotonin Reuptake Inhibitors: Qualitative Study,” British Journal of Psychiatry 195, no. 3 (2009): 211–17; Adam Opbroek et al., “Emotional Blunting Associated with SSRI-Induced Sexual Dysfunction. Do SSRIs Inhibit Emotional Responses?” International Journal of Neuropsychopharmacology 5, no. 2 (2002): 147–51.

27 SSRIs affect emotional processing: Price et al., “Emotional Side-Effects of Selective Serotonin Reuptake Inhibitors,” 211–17.

27 medications often can: The exception here is if you’ve had more than one major depressive episode. Then the current recommendation is that you get on and stay on your antidepressant medication to avoid a likely relapse.

28 A clear, visible sign: Robert W. Levenson, “Blood, Sweat, and Fears,” Annals of the New York Academy of Sciences 1000, no. 1 (2003): 348–66.

28 In one study of medicated women: Robert J. Gregory et al., “Ethical Dilemmas in Prescribing Antidepressants,” Archives of General Psychiatry 58, no. 11 (2001): 1085.

29 stuffing down your feelings: Gabor Maté, When the Body Says No: The Cost of Hidden Stress (New York: Random House, 2011).

29 The suppression of anger: William T. Riley et al., “Anger and Hostility in Depression,” Journal of Nervous and Mental Disease 177, no. 11 (1989): 668–74.

29 People who’ve experienced depression: Cindy L. Brody et al., “Experiences of Anger in People Who Have Recovered from Depression and Never-Depressed People,” Journal of Nervous and Mental Disease 187, no. 7 (1999): 400–405.

29 Depressed patients have higher levels: M. Weissman et al., “Clinical Evaluation of Hostility in Depression,” American Journal of Psychiatry (1971): 12841–46; Roger C. Bland and Helene Orn, “Family Violence and Psychiatric Disorder,” Canadian Journal of Psychiatry/La Revue canadienne de psychiatrie 31, no. 2 (1986): 129–37.; K. B. Koh et al., “Predominance of Anger in Depressive Disorders Compared with Anxiety Disorders and Somatoform Disorders,  Journal of Clinical Psychiatry (2002): 63486–92.

29 the more anger, the more severe: A. P. Schless et al., “Depression and Hostility,” Journal of Nervous and Mental Disease 159, no. 2 (1974): 81–100.

29 In an examination of women’s employment reviews: Keiran Snyder, “The Abrasiveness Trap: High-Achieving Men and Women Are Described Differently in Reviews,” Fortune, August 26, 2014, http://­fortune.com/2014/08/26/performance-review-gender-bias/.

29 SSRIs reduce aggression: Menahem Krakowski, “Violence and Serotonin: Influence of Impulse Control, Affect Regulation, and Social Functioning,” Journal of Neuropsychiatry and Clinical Neurosciences 15, no. 3 (2003): 294–305.

30 SSRIs augment social dominance: S. Tse Wai and Alyson J. Bond, “Serotonergic Intervention Affects Both Social Dominance and Affiliative Behavior,” Psychopharmacology 161, no. 3 (2002): 324–30.

30 elevating an animal’s status: M. J. Raleigh et al., “Serotonergic Mechanisms Promotes Dominance Acquisition in Adult Male Vervet Monkeys,” Brain Research 559 (1991): 181–90.

30 girls who hold on to their assertiveness: Maté, When the Body Says No.

30 In the nineteenth century: Pierre Janet, The Major Symptoms of Hysteria (New York: Macmillan, 1907).

30 One treatment for hysteria: Rachel Maines, The Technology of Orgasm: “Hysteria,” the Vibrator, and Women’s Sexual Satisfaction (Baltimore: Johns Hopkins University Press, 1999).

30–31 removal of the clitoris: Elizabeth Sheehan, “Victorian Clitoridectomy: Isaac Baker Brown and His Harmless Operative Procedure,” Medical Anthropology Newsletter 12, no. 4 (1981): 9–15.

31 Epidemiological studies show: Linda LeResche, “Epidemiologic Perspectives on Sex Differences in Pain,” in Sex, Gender, and Pain, ed. R. B. Fillingim (Seattle: IASP Press, 2000), 233–49; Linda LeResche, “Epidemiology of Pain Conditions with Higher Prevalence in Women,” in May L. Chin et al., eds., Pain in Women (New York: Oxford Univeristy Press, 2013); M. Von Korff et al., “An Epidemiologic Comparison of Pain Complaints, Pain 32 (1988): 173–83.

31 Men are less apt: Ann Vincent et al., “Prevalence of Fibromyalgia: A Population-Based Study in Olmsted County, Minnesota, Utilizing the Rochester Epidemiology Project,” Arthritis Care & Research 65, no. 5 (2013): 786–92.

31 Women’s sensitivities extend: A. M. Unruh, “Gender Variations in Clinical Pain Experience,” Pain 65 (1996): 123–67; Marieke Niesters et al., “Sex Differences in Analgesic Responses,” in Chin et al., eds., Pain in Women.

32 overwhelming laboratory evidence: Mordechai Averbuch, and Meyer Katzper, “A Search for Sex Differences in Response to Analgesia,” Archives of Internal Medicine 160, no. 22 (2000): 3424–28;  R. B. Fillingim and W. Maixner, “Gender Differences in Response to Noxious Stimuli,” Pain Forum 4 (1995): 209–21; R. B. Fillingim and T. J. Ness, “Sex-Related Hormonal Influences on Pain and Analgesic Responses,” Neuroscience & Biobehavioral Reviews 24, no. 4 (2000): 485–501; Riley, “Anger and Hostility in Depression,” 668–74.

32 Women are also more apt: Cosgrove et al., “Evolving Knowledge of Sex Differences,” 847–55.

32 our hormones: M. B. Dawson-Basoa and A. R. Gintzler, “17-Beta-Estradiol and Progesterone Modulate an Intrinsic Opioid Analgesic System,” Brain Research 601 (1993): 241–45; Yolanda R. Smith et al., “Pronociceptive and Antinociceptive Effects of Estradiol Through Endogenous Opioid Neurotransmission in Women,” Journal of Neuroscience 26, no. 21 (2006): 5777–85.

32 where we are in our menstrual cycle: Zsuzsanna Wiesenfeld-Hallin, “Sex Differences in Pain Perception,” Gender Medicine 2, no. 3 (2005): 137–45; Cristina Tassorelli et al., “Changes in ­Nociceptive Flexion Reflex Threshold Across the Menstrual Cycle in Healthy Women,” Psychosomatic Medicine 64, no. 4 (2002): 621–26.

32 Our psyches are silently screaming: Maté, When the Body Says No.

32 In the journal Pain: J. S. Mogil and M. L. Chanda, “The Case for the Inclusion of Female Subjects in Basic Science Studies of Pain,” Pain 117 (2005): 1–5.

32 reports of chest pain: J. Ayanian and A. Epstein, “Differences in the Use of Procedures Between Women and Men Hospitalized for Coronary Heart Disease,” New England Journal of Medicine 325 (1991): 221–25; M. Delborg and K. Swedberg, “Acute Myocardial Infarction: Difference in the Treatment Between Men and Women,” Quality Assurance in Health Care 5 (1993): 261–65.

32 lung cancer: C. Wells and A. Feinstein, “Detection Bias in the Diagnostic Pursuit of Lung Cancer,” American Journal of Epidemiology 128 (1988): 1016–26.

32 in general complaints: K. Armitage et al., “Responses of Physicians to Medical Complaints in Men and Women,” JAMA 241 (1979): 2186–87; S. Colameco et al., “Sex Bias in the Assessment of Patient Complaints,” Journal of Family Practice 16 (1983): 1117–21.

32 psychiatric complaints: Ann A. Hohmann, “Gender Bias in Psychotropic Drug Prescribing in Primary Care,” Medical Care 27, no. 5 (1989): 478–90; Cynthia M. Hartung and Thomas A. Widiger, “Gender Differences in the Diagnosis of Mental Disorders: Conclusions and Controversies of the DSM–IV,” Psychological Bulletin 123, no. 3 (1998): 260.

32 Until recently, surgeons knew much less: Jennifer Berman and Laura Berman, For Women Only: A Revolutionary Guide to Reclaiming Your Sex Life (New York: Macmillan, 2001), 127.

33 Eight of ten drugs withdrawn: J. Heinrich et al., “Drug Safety: Most Drugs Withdrawn in Recent Years Had Greater Health Risks for Women,” United States General Accounting Office, Washington, D.C., 2001.

33 After twenty years on the market: David J. Greenblatt et al., “Gender Differences in Pharma­cokinetics and Pharmacodynamics of Zolpidem Following Sublingual Administration,” The Journal of Clinical Pharmacology 54, no. 3 (2014): 282–90.

Chapter Two: Feeling Bitchy Like Clockwork

36 Somewhere between 3 and 8 percent: Lorraine Dennerstein et al., “Epidemiology of Premenstrual Symptoms and Disorders,” Menopause International 18, no. 2 (2012): 48–51.

37 when you ovulate: The feeling of ovulation is called mittelschmerz, German for “middle pain.” It is a short, sharp pain usually felt in one corner of your lower pelvis. The side may alternate monthly, but not always.

37 what to expect: Google “Monthly Mood Cube” for a cute idea.

37 The peak estrogen levels: Elizabeth Hampson, “Estrogen-Related Variations in Human Spatial and ­Articulatory-Motor Skills,” Psychoneuroendocrinology 15, no. 2 (1990): 97–111.

40 there is some evidence: Christiane Northrup, Women’s Bodies, Women’s Wisdom: Creating Physical and Emotional Health and Healing (New York: Bantam, 1994).

40 Because of lower serotonin levels: Eliza Reynolds, Mothering and Daughtering: Keeping Your Bond Strong Through the Teen Years (Sounds True, 2013).

41 There are studies that claim: Debra A. Zellner et al., “Chocolate Craving and the Menstrual Cycle” Appetite 42, no. 1 (2004): 119–21.

41 your body requires more calories: Roy F. Baumeister and John Tierney, Willpower: Rediscovering the Greatest Human Strength (New York: Penguin, 2011).

41 your magnesium levels are low: Kristen Bruinsma and Douglas L. Taren, “Chocolate: Food or Drug?” Journal of the American Dietetic Association 99, no. 10 (1999): 1249–56.

41 In depression and in PMS: Richard J. Wurtman and Judith J. Wurtman, “Carbohydrate Craving, Obesity and Brain Serotonin,” Appetite 7 (1986): 99–103; Richard J. Wurtman and Judith J. Wurtman, “Do Carbohydrates Affect Food Intake Via Neurotransmitter Activity?” Appetite 11 (1988): 42–47.

42 Cardio, in particular, can help: Amanda Daley, “Exercise and Premenstrual Symptomatology: A Comprehensive Review,” Journal of Women’s Health 18, no. 6 (2009): 895–99.

43 when you started having sex: Winnifred B. Cutler et al., “Sexual Behavior Frequency and Menstrual Cycle Length in Mature Premenopausal Women,” Psychoneuroendocrinology 4, no. 4 (1979): 297–309.

43 If you started earlier: Winnifred Berg Cutler et al., “Sporadic Sexual Behavior and Menstrual Cycle Length in Women,” Hormones and Behavior 14, no. 2 (1980): 163–72; Winnifred Berg Cutler et al., “Sexual Behavior Frequency and Biphasic Ovulatory Type Menstrual Cycles,” Physiology & Behavior 34, no. 5 (1985): 805–10.

43 Weekly sex: Cutler et al., “Sexual Behavior Frequency and Menstrual Cycle Length,” 297–309; Cutler et al., “Sexual Behavior Frequency and Biphasic Ovulatory Type Menstrual Cycles,”

805–10.

43 In a group of women: W. B. Cutler et al., “Coitus and Menstruation in Perimenopausal Women,” Journal of Psychosomatic Obstetrics & Gynecology 17, no. 3 (1996): 149–57.

43 antidepressant withdrawal: Junk food is addictive, our phones are addictive, cigarettes are addictive. Why would we think antidepressants are any different?

45 In one study of women: H. Joffe et al., “Impact of Oral Contraceptive Pill Use on Premenstrual Mood: Predictors of Improvement and Deterioration,” American Journal of Obstetrics & Gynecology 189 (2003): 1523–30.

45 estrogen causes the manufacture: Barbara E. H. Sumner and George Fink, “Estrogen Increases the Density of 5-Hydroxytryptamine 2A Receptors in Cerebral Cortex and Nucleus Accumbens in the Female Rat,” Journal of Steroid Biochemistry and Molecular Biology 54, no. 1 (1995): 15–20.

45 About a third of women: Merja Viikki et al., “Interaction Between Two HTR2A Polymorphisms and Gender Is Associated with Treatment Response in MDD,” Neuroscience Letters 501, no. 1 (2011): 20–24.

45–46 Synthetic progestin is horrible: Lila Nachtigal, personal communication with author, June 4, 2014.

46 The oral contraceptives Yaz and Yasmin: Wolfgang Oelkers, “Drospirenone, a Progestogen with Antimineralocorticoid Properties: A Short Review,” Molecular and Cellular Endocrinology 217, no. 1 (2004): 255–61.

46 synthetic hormones seem to interfere: P. W. Adams et al., “Effect of Pyridoxine Hydrochloride upon ­Depression Associated with Oral Contraception,” Lancet 301, no. 7809 (1973): 897–904.

47 Taking extra estrogen: Peter R. Casson et al., “Effect of Postmenopausal Estrogen Replacement on Circulating Androgens,” Obstetrics & Gynecology 90, no. 6 (1997): 995–98.

47 It gets worse: a research study: Panzer et al., “Impact of Oral Contraceptives on Sex Hormone-Binding Globulin and Androgen Levels: A Retrospective Study in Women with Sexual Dysfunction,” Journal of Sexual Medicine 3 (2006): 104–13

47 he told me it never returns: Irwin Goldstein, personal communication with author, June 4,

2014.

47 Part of every woman’s monthly cycle: Stephanie H. M. Van Goozen et al., “Psychoendocrinological Assessment of the Menstrual Cycle: The Relationship Between Hormones, Sexuality, and Mood,” Archives of Sexual Behavior 26, no. 4 (1997): 359–82.

48 a book called Sexy Mamas: Cathy Winks and Anne Semans, Sexy Mamas: Keeping Your Sex Life Alive While Raising Kids (Novato, CA: New World Library, 2004).

49 Studies show that men are more: See Andrew J. Elliot, Tobias Greitemeyer, and Adam D. Pazda, “Women’s Use of Red Clothing As a Sexual Signal in Intersexual Interaction,” Journal of Experimental Social Psychology 49, no. 3 (2013): 599–602, for a review.

49 Greater feelings of attractiveness: Juan J. Tarín and Vanessa Gómez-Piquer, “Do Women Have a Hidden Heat Period?” Human Reproduction 17, no. 9 (2002): 2243–48.

49 Oxytocin peaks: M. D. Mitchell et al., “Plasma Oxytocin Concentrations During the Menstrual Cycle,” European Journal of Obstetrics & Gynecology and Reproductive Biology 12, no. 3 (1981): 195–200.

49 pupils even dilate: Bruno Laeng and Liv Falkenberg, “Women’s Pupillary Responses to Sexually Significant Others During the Hormonal Cycle,” Hormones and Behavior 52, no. 4 (2007): 520–30.

49 Women who are ovulating: Christopher Ryan and Cacilda Jethá, Sex at Dawn: The Prehistoric Origins of Modern Sexuality (New York: HarperCollins, 2010).

49 Women feel more attractive: Tarín and Gómez-Piquer, “Do Women Have a Hidden Heat Period?” 2243–48.

49 men are able to tell which women: Martie G. Haselton et al., “Ovulatory Shifts in Human Female Ornamentation: Near Ovulation, Women Dress to Impress,” Hormones and Behavior 51, no. 1 (2007): 40–45.

49 In studies, men pay strippers: Ryan and Jethá, Sex at Dawn.

50 Women prefer men with a lower voice: Jillian J. M. O’Connor et al., “Perceptions of Infidelity Risk Predict Women’s Preferences for Low Male Voice Pitch in Short-Term over Long-Term Relationship Contexts,” Personality and Individual Differences 56 (2014): 73–77.

50 When women are ovulating: Ian S. Penton-Voak et al. “Menstrual Cycle Alters Face Preference,” Nature 399, no. 6738 (1999): 741–42.

50 When not fertile, women still: Randy Thornhill and Steven W. Gangestad, The Evolutionary Biology of Human Female Sexuality (Oxford University Press, 2008); Steven W. Gangestad and Randy Thornhill, “Human Oestrus,” Proceedings of the Royal Society B: Biological Sciences 275, no. 1638 (2008): 991–1000.

50 Women find classically masculine faces: Tarín and Gómez-Piquer, “Do Women Have a Hidden Heat Period?” 2243–48.

50 Fertile women are also more attracted: Jan Havlíˇcek et al., “Women’s Preference for Dominant Male Odor: Effects of Menstrual Cycle and Relationship Status,” Biology Letters 1, no. 3 (2005): 256–59; Steven W. Gangestad et al., “Women’s Preferences for Male Behavioral Displays Change Across the Menstrual Cycle,” Psychological Science 15, no. 3 (2004): 203–7.

51 Partnered women are more likely: Havlíˇcek et al., “Women’s Preference for Dominant Male Odor,” 256–59.

51 There’s no midcycle peak: Andrea Salonia et al., “Menstrual Cycle-Related Changes in Plasma Oxytocin Are Relevant to Normal Sexual Function in Healthy Women,” Hormones and Behavior 47, no. 2 (2005): 164–69.

51 As far as the brain is concerned: Penton-Voak et al., “Menstrual Cycle Alters Face Preference,” 741–42; Benedict C. Jones et al., “Effects of Menstrual Cycle Phase on Face Preferences,” Archives of Sexual Behavior 37, no. 1 (2008): 78–84; Alexandra Alvergne and Virpi Lummaa, “Does the Contraceptive Pill Alter Mate Choice in Humans?” Trends in Ecology & Evolution 25, no. 3 (2010): 171–79.

51 weaker or no preferences for facial: A. C. Little et al., “Partnership Status and the Temporal Context of Relationships Influence Human Female Preferences for Sexual Dimorphism in Male Face Shape,” Proceedings of the Royal Society of London, Series B: Biological Sciences 269, no. 1496 (2002): 1095–1100.

51 vocal masculinity: Penton-Voak et al., “Menstrual Cycle Alters Face Preference,” 741–42.

51 Men are actually more likely to fall in love: Arthur Aron et al., “Reward, Motivation, and Emotion Systems Associated with Early-Stage Intense Romantic Love,” Journal of Neurophysiology 94, no. 1 (2005): 327–37.

52 Women have a more: Brizendine, The Female Brain.

52 more brain space devoted: M. Bensafi et al., “Sex-Steroid Derived Compounds Induce Sex-Specific ­Effects on Autonomic Nervous System Function in Humans,” Behavioral Neuroscience 117, no. 6 (2003): 1125; Suma Jacob et al., “Context-Dependent Effects of Steroid Chemosignals on Human Physiology and Mood,” Physiology & Behavior 74, no. 1 (2001): 15–27.

53 Too-similar immune systems: Christine E. Garver-Apgar et al., “Major Histocompatibility Complex Alleles, Sexual Responsivity, and Unfaithfulness in Romantic Couples,” Psychological Science 17, no. 10 (2006): 830–35.

53 if a woman partners with a man: Ibid.

54 they like her scent more: Jan Havlíˇcek et al., “Non-Advertized Does Not Mean Concealed: Body Odor Changes Across the Human Menstrual Cycle,” Ethology 112, no. 1 (2006): 81–90.

54 If she’s on the Pill: Seppo Kuukasjärvi et al., “Attractiveness of Women’s Body Odors over the Menstrual Cycle: The Role of Oral Contraceptives and Receiver Sex,” Behavioral Ecology 15, no. 4 (2004): 579–84.

54 In a replay of the sweaty T-shirt experiment: C. Wedekind et al., “MHC-Dependent Mate Preferences in Humans,” Proceedings of the Royal Society of London 260 (1995): 245–49; Randy Thornhill and Steven W. Gangestad, “Do Women Have Evolved Adaptation for Extra-Pair Copulation?” in Evolutionary Aesthetics, Springer Berlin Heidelber (2003): 341–68; Jan Havlíˇcek and S. Craig Roberts, “MHC-Correlated Mate Choice in Humans: A Review,” Psychoneuroendocrinology 34, no. 4 (2009): 497–512.

54 Women who were on oral contraceptives: S. Craig Roberts et al., “Relationship Satisfaction and Outcome in Women Who Meet Their Partner While Using Oral Contraception,” Proceedings of the Royal Society B: Biological Sciences 279, no. 1732 (2012): 1430–36.

Chapter Three: This Is Your Brain on Love

59 falling in love is the neural mechanism: Helen Fisher, Why We Love: The Nature and Chemistry of Romantic Love (New York: Macmillan), 2004.

60 Experiments with prairie voles: Brandon J. Aragona et al., “A Critical Role for Nucleus Accumbens Dopamine in Partner-Preference Formation in Male Prairie Voles,” Journal of Neuroscience 23, no. 8 (2003): 3483–90.

60 Helen Fisher’s brain scans: Helen Fisher et al., “Romantic Love: An fMRI Study of a Neural Mechanism for Mate Choice,” Journal of Comparative Neurology 493, no. 1 (2005): 58–62.

60 “motor of the mind”: J. R. Villablanca, “Why Do We Have a Caudate Nucleus?” Acta Neurobiol Exp (Wars) 70, no. 1 (2010): 95–105.

61 The Rules: Ellen Fein and Sherrie Schneider, The Rules: Time-Tested Secrets for Capturing the Heart of Mr. Right (New York: Warner Books, 1996).

61 getting the reward too early: Shunsuke Kobayashi and Wolfram Schultz, “Influence of Reward Delays on Responses of Dopamine Neurons,” Journal of Neuroscience 28, no. 31 (2008): 7837–46.

61 Increased levels of these two chemicals: Anne M. Etgen et al., “Estradiol and Progesterone Modulation of Norepinephrine Neurotransmission: Implications for the Regulation of Female Reproductive Behavior,” Journal of Neuroendocrinology 4, no. 3 (1992): 255–71.

62 the “molecule of attraction”: Fisher, Why We Love.

62 also found in a group of drugs: Alexander Shulgin and Ann Shulgin, Pihkal: A Chemical Love Story (Berkeley: Transform Press, 1991).

62 a short-term antidepressant: Hector Sabelli et al., “Sustained Antidepressant Effect of PEA Replacement,” Journal of Neuropsychiatry and Clinical Neurosciences 8, no. 2 (1995): 168–71.

62 present in good chocolates: John P. Chaytor et al., “The Identification and Significance of 2-Phenylethylamine in Foods,” Journal of the Science of Food and Agriculture 26, no. 5 (1975): 593–98.

62 may also spike during orgasm: Hoyle Leigh, “Basic Foundations of Diagnosis, Psychiatric Diagnosis and Final Common Pathway Syndromes,” in Handbook of Consultation-Liaison Psychiatry (New York: Springer, 2007), 53–73.

62 The levels of the sex hormones: Fisher, Why We Love.

62 Estrogen and progesterone: Schumacher, 1990.

62–63 higher levels of circulating testosterone: Rainer Knussmann et al., “Relations Between Sex Hormone Levels and Sexual Behavior in Men,” Archives of Sexual Behavior 15, no. 5 (1986): 429–45; Jan L. Shifren et al., “Transdermal Testosterone Treatment in Women with Impaired Sexual Function After Oophorectomy,” New England Journal of Medicine 343, no. 10 (2000): 682–88; Adriaan Tuiten et al., “Time Course of ­Effects of Testosterone Administration on Sexual Arousal in Women,” Archives of General Psychiatry 57, no. 2 (2000): 149–53; Andrea M. Isidori et al., “Effects of Testosterone on Sexual Function in Men: Results of a Meta-Analysis,” Clinical Endocrinology 63, no. 4 (2005): 381–94.

63 inhaling male pheromones: Erin D. Gleason et al., “Testosterone Release and Social Context: When It Occurs and Why,” Frontiers in Neuroendocrinology 30, no. 4 (2009): 460–69.

63 Just thinking about your new guy: Katherine L. Goldey and Sari M. van Anders, “Sexy Thoughts: Effects of Sexual Cognitions on Testosterone, Cortisol, and Arousal in Women,” Hormones and Behavior 59, no. 5 (2011): 754–64.

63 men who are falling in love: D. Marazziti et al., “Alteration of the Platelet Serotonin Transporter in Romantic Love,” Psychological Medicine 29, no. 3 (1999): 741–45.

63 same-sex couples can and do: Michael W. Johnston and Alan P. Bell, “Romantic Emotional Attachment: Additional Factors in the Development of the Sexual Orientation of Men,” Journal of Counseling & Development 73, no. 6 (1995): 621–25; Letitia Anne Peplau, “Rethinking Women’s Sexual Orientation: An Interdisciplinary, Relationship-Focused Approach,” Personal Relationships 8, no. 1 (2001): 1–19.

64 Smiling babies and hugs: Tracey A. Baskerville, “Dopamine and Oxytocin Interactions Underlying Behaviors: Potential Contributions to Behavioral Disorders,” CNS Neuroscience & Therapeutics 16, no. 3 (2010): e92-e123.

64 it can help to speed healing: Kerstin Uvnas Moberg and Roberta Francis, The Oxytocin Factor: Tapping the Hormone of Calm, Love, and Healing (Cambridge, MA: Da Capo Press, 2003); Courtney E. Detillion et al., “Social Facilitation of Wound Healing,” Psychoneuroendocrinology 29, no. 8 (2004): 1004–11.

64 Women have more oxytocin receptors: M. M. McCarthy, “Estrogen Modulation of Oxytocin and Its Relation to Behavior,” Advances in Experimental Medicine and Biology 395 (1994): 235–45.

64 In experiments, people given oxytocin: Michael Kosfeld et al., “Oxytocin Increases Trust in Humans,” Nature 435, no. 7042 (2005): 673–76; Paul J. Zak et al., “Oxytocin Increases Generosity in Humans,” PLoS One 2, no. 11 (2007): e1128.

64 people who are touched while spoken to: Paul J. Zak, The Moral Molecule: How Trust Works. (New York: Penguin, 2012).

64 When people fall in love, their fear circuitry: Fisher, Why We Love.

64 brain-derived neurotrophic factor: E. Emanuele et al., “Raised Plasma Nerve Growth Factor Levels Associated with Early-Stage Romantic Love,” Psychoneuroendocrinology, September 5, 2005.

65 “obliterated and replaced”: Norman Doidge, The Brain That Changes Itself (New York: Penguin, 2007), 113.

65 Blood serotonin levels in those newly in love: Marazziti et al., “Alteration of the Platelet Serotonin Transporter in Romantic Love,” Psychological Medicine 29, no. 3 (1999): 741–45.

66 SSRIs interfere with mating: Helen E. Fisher and J. Anderson Thomson Jr., “Lust, Romance, ­Attachment: Do the Side Effects of Serotonin-Enhancing Antidepressants Jeopardize Romantic Love, Marriage, and Fertility?” Evolutionary Cognitive Neuroscience (2007): 245.

66 Female rats treated chronically with SSRIs: J. V. Matuszczyk et al., “Subchronic Administration of Fluoxetine Impairs Estrous Behavior in Intact Female Rats,” Neuropsychopharmacology 19 (1998): 492–98.

66 women on SSRIs rate men as less attractive: Justin Garcia, e-mail message to author, September 8, 2014, September 9, 2014, September 10, 2014.

66 “less likely to find those”: Justin Garcia, e-mail message to the author, September 8, 2014.

67 “Scientists think the fickle female orgasm”: Helen Slater, “True Love,” National Geographic, February 2006.

67 But with lust, a biological drive: Fisher, Why We Love.

67 Even flirting seems to have some basis: Sari M. van Anders and Katherine L. Goldey, “Testosterone and Partnering Are Linked Via Relationship Status for Women and ‘Relationship Orientation’ for Men,” Hormones and Behavior 58, no. 5 (2010): 820–26.

67 “almost any semi-appropriate partner”: Fisher, Why We Love, 78.

68 surging testosterone levels in an adolescent girl: C. T. Halpern and J. R. Udry, “Testosterone Predicts Initiation of Coitus in Adolescent Females,” Psychosomatic Medicine 59, no. 2 (1997): 161–71.

68 Rising testosterone levels: M. I. Gonzalez et al., “Interactions Between 5-Hydroxytryptamine (5-HT) and Testosterone in the Control of Sexual and Nonsexual Behavior in Male and Female Rats,” Pharmacology Biochemistry and Behavior 47, no. 3 (1994): 591–601.

69 There is a strong desire in women: Marc H. Hollender, “The Need or Wish to Be Held,” Archives of ­General Psychiatry 22, no. 5 (1970): 445.

69 Many of us will use sex as a means: Marc H. Hollender et al., “Body Contact and Sexual Enticement,” ­Archives of General Psychiatry 20, no. 2 (1969): 188.

69 A common complaint among men: Pat Love and J. T. Brown, “Creating Passion and Intimacy,” in The ­Intimate Couple, ed. Jon Carlson and Len Sperry (Psychology Press, 1999): 55–65.

71 mounting evidence that sexual pleasure: James G. Pfaus, “Reviews: Pathways of Sexual Desire,” Journal of Sexual Medicine 6, no. 6 (2009): 1506–33; Carolin Klein et al., “Circulating Endocannabinoid Concentrations and Sexual Arousal in Women,” Journal of Sexual Medicine 9, no. 6 (2012): 1588–1601.

71 The beginning of sexual pleasure: Daniel Bergner, What Do Women Want?: Adventures in the Science of Female Desire (New York: Ecco, 2013).

71 Peaking at orgasm, oxytocin: D. L. Lefebvre et al., “Uterine Oxytocin Gene Expression. I. ­Induction During Pseudopregnancy and the Estrous Cycle,” Endocrinology 134, no. 6 (1994): 2556–61.

72 (They can, as long as their vagus nerve): Barry R. Komisaruk et al., “Brain Activation During Vaginocervical Self-Stimulation and Orgasm in Women with Complete Spinal Cord Injury: fMRI Evidence of Mediation by the Vagus Nerves,” Brain Research 1024, no. 1 (2004): 77–88.

72 Leading up to orgasm, a series of brain blood flow changes: B. R. Komisaruk et al., “An fMRI Time-Course Analysis of Brain Regions Activated During Self-Stimulation to Orgasm in Women,” Society for Neuroscience (2010): 285.6.

73 release of oxytocin: The paraventricular nucleus.

73 underlies reward seeking: The nucleus accumbens.

Chapter Four: Marriage and Its Discontents

75 study comparing the serotonin levels: Donatella Marazziti, “The Neurobiology of Love,” Current Psychiatry Reviews 1, no. 3 (2005): 331–35.

75 Men’s testosterone levels are lower: Peter B. Gray et al., “Human Male Pair Bonding and Testosterone,” Human Nature 15, no. 2 (2004): 119–31.

76 Birds that are given an extra dose: Kathleen E. Hunt et al., “Endocrine Influences on Parental Care During a Short Breeding Season: Testosterone and Male Parental Care in Lapland Longspurs (Calcarius Lapponicus),” Behavioral Ecology and Sociobiology 45, no. 5 (1999): 360–69.

76 men with lower testosterone levels more responsive: Anne E. Story et al., “Hormonal Correlates of ­Paternal Responsiveness in New and Expectant Fathers,” Evolution and Human Behavior 21, no. 2 (2000): 79–95.

76 “paternal effort”: Peter B. Gray et al., “Marriage and Fatherhood Are Associated with Lower Testosterone in Males,” Evolution and Human Behavior 23, no. 3 (2002): 193–201; Christopher W. Kuzawa et al., ­“Fatherhood, Pairbonding and Testosterone in the Philippines,” Hormones and Behavior 56, no. 4 (2009): 429–35.

76 Emotional connectedness: Both men and women have each hormone, but because of estrogen and testosterone, oxytocin is more of an issue in women and vasopressin is more of an issue in men.

77 In monogamous prairie voles: Miranda M. Lim et al., “Ventral Striatopallidal Oxytocin and Vasopressin V1a Receptors in the Monogamous Prairie Vole (Microtus Ochrogaster),” Journal of Comparative Neurology 468, no. 4 (2004): 555–70.

77 the “monogamy gene”: Brizendine, The Female Brain.

77 the shorter gene is seen in autism: A. Meyer-Lindenberg et al, “Genetic Variants in AVPR1A Linked to Austism Predict Amygdala Activation and Personality Traits in Healthy Humans,” Molecular Psychiatry 14, no. 10 (2008): 968–75.

77 In Helen Fisher’s brain-imaging studies: Arthur Aron et al., “Reward, Motivation, and Emotion Systems Associated with Early-Stage Intense Romantic Love,” Journal of Neurophysiology 94, no. 1 (2005): 327–37.

77 the “anchoring gaze”: Deborah Tannen, Talking from 9 to 5!: How Women’s and Men’s Conversational Styles Affect Who Gets Heard, Who Gets Credit, and What Gets Done at Work (New York: Simon & Schuster Audio, 1994).

77 Looking away, turning away: Ned H. Kalin et al., “The Role of the Central Nucleus of the Amygdala in Mediating Fear and Anxiety in the Primate,” Journal of Neuroscience 24, no. 24 (2004): 5506–15.

77 trigger stress hormones: Cortisol and norepinephrine.

77 We are wired to connect: Matthew D. Lieberman, Social: Why Our Brains Are Wired to Connect ­(Oxford University Press, 2013).

77 to need other people: Myron A. Hofer, “The Psychobiology of Early Attachment,” Clinical Neuroscience Research 4, no. 5 (2005): 291–300; Myron A. Hofer, “Psychobiological Roots of Early Attachment,” Current Directions in Psychological Science 15, no. 2 (2006): 84–88.

77 In more than ninety countries surveyed: Helen E. Fisher, Anatomy of Love: The Natural History of ­Monogamy, Adultery, and Divorce (New York: Simon & Schuster, 1992).

78 Since 2000 that number has risen: Jackie Calmes, “To Hold Senate, Democrats Rely on Single Women,” New York Times, July 2, 2014.

78 First-time marriages end in divorce: Natalie Angier, “The Changing American Family,” New York Times, November 25, 2013.

78 The Maslow hierarchy of human needs: Abraham Harold Maslow, “A Theory of Human Motivation,” Psychological Review 50, no. 4 (1943): 370.

78 we’re looking for our partnership: Eli Finkel, “The All-or-Nothing Marriage,” New York Times, February 14, 2014.

78 The quality of a marriage: Mark A. Whisman and Martha L. Bruce, “Marital Dissatisfaction and Incidence of Major Depressive Episode in a Community Sample,” Journal of Abnormal Psychology 108, no. 4 (1999): 674; Mark A. Whisman, “The Association Between Depression and Marital Dissatisfaction,” in Marital and Family Processes in Depression: A Scientific Foundation for Clinical Practice, Steven R. H. Beach (Washington, DC: American Psychological Association, 2001), 3–24.

78 the positive effects of a strong union: Linda Waite and Maggie Gallagher, The Case for Marriage: Why Married People Are Happier, Healthier and Better Off Financially (New York: Random House, 2002).

78 strengthen over time: Christine M. Proulx et al., “Marital Quality and Personal Well-Being: A Meta-­Analysis,” Journal of Marriage and Family 69, no. 3 (2007): 576–93.

80 Any reminder of an early attachment failure: Marion Solomon and Stan Tatkin, Love and War in Intimate Relationships: Connection, Disconnection, and Mutual Regulation in Couple Therapy, Norton Series on Interpersonal Neurobiology (New York: W. W. Norton & Company, 2011); Harville Hendrix, Getting the Love You Want: A Guide for Couples (New York: Macmillan, 2007).

80 Higher cognitive functions are shut down: Daniel J. Siegel, “An Interpersonal Neurobiology Approach to Psychotherapy,” Psychiatric Annals 36, no. 4 (2006): 248.

81 conscious couples enable positive, healthy aspects: Harville Hendrix and Helen LaKelly Hunt, Making Marriage Simple: 10 Truths for Changing the Relationship You Have into the One You Want (New York: Random House, 2013).

81 The number of women who are: Pew Research Center, “Mothers as the Sole or Primary Provider,” May 29, 2013.

81 A recent business school survey: Iraj Mahdavi, “Comparing Men’s and Women’s Definition of Success,” Journal of Behavioral Studies in Business 3 (2010): 1–8.

82 Sharing earnings and household chores: Lynn Prince Cooke, “ ‘Doing’ Gender in Context: Household ­Bargaining and Risk of Divorce in Germany and the United States,” American Journal of Sociology 112, no. 2 (2006): 442–72.

82 more likely to report marital troubles: Marianne Bertrand et al., “Gender Identity and Relative Income Within Household,” (working paper, National Bureau of Economic Research, number 19023, 2013).

82 if the wife earns around 40 percent: Cooke, “ ‘Doing’ Gender in Context,” 442–72.

82 the egalitarian marriage: Lori Gottlieb, “Does a More Equal Marriage Mean Less Sex?” New York Times, February 6, 2014.

82 When our husbands are doing dishes: Sabino Kornrich et al., “Egalitarianism, Housework, and Sexual Frequency in Marriage,” American Sociological Review 78, no. 1 (2013): 26–50.

83 the longer a couple stays together: Gary L. Hansen, “Extradyadic Relations During Courtship,” Journal of Sex Research 23 (1987): 382–90.

83 a spike in the numbers: James D. Wiggins and Doris A. Lederer, “Differential Antecedents of Infidelity in Marriage,” American Mental Health Counselors Association Journal, no. 6 (1984): 152–61.

83 Women are more likely to cheat: Pamela Druckerman, Lust in Translation: The Rules of Infidelity from Tokyo to Tennessee (New York: Penguin Press, 2007).

84 For men, the likelihood of an affair: Chien Liu, “A Theory of Marital Sexual Life,” Journal of Marriage and Family 62, no. 2 (2000): 363–74.

84 High-risk times for men: Mark A.Whisman et al., “Predicting Sexual Infidelity in a Population-Based Sample of Married Individuals,” Journal of Family Psychology 21, no. 2 (2007): 320–24.

84 Very few animals: Ryan and Jethá, Sex at Dawn.

84 Pair-bonding is rare: I. Tsapelas, H. E. Fisher, and A. Aron, “Infidelity: When, Where, Why,” in The Dark Side of Close Relationships II, W. R. Cupach and B. H. Spitzberg (New York: Routledge, 2010), 175–96.

84 Penguins are monogamous only: J. F. Wittenberger and R. L. Tilson, “The Evolution of Monogamy: ­Hypotheses and Evidence,” Annual Review of Ecology and Systematics 11 (1980): 197–232; D. W. Mock and M. Fujioka, “Monogamy and Long-Term Bonding in Vertebrates,” Trends in Ecology and Evolution 5, no. 2 (1990): 39–43.

84 we didn’t descend from apes: Michael J. Benton, Vertebrate Paleontology (Wiley-Blackwell, 2005).

85 Chimps and bonobos: Anne E. Pusey, “Of Genes and Apes: Chimpanzee Social Organization and Reproduction,” Tree of Origin: What Primate Behavior Can Tell Us About Human Social Evolution (2001): 9–38.

85 Humans and bonobos: Ryan and Jethá, Sex at Dawn.

85 In bonobo troops: Barbara Fruth and Gottfried Hohmann, “Social Grease for Females? Same-Sex Genital Contacts in Wild Bonobos,” in Volker Sommer and Paul L. Vasey, eds., Homosexual Behaviour in Animals: An Evolutionary Perspective (New York: Cambridge University Press, 2006): 294–315.

85 the bonobo clitoris: Katarina Nolte, Mystery Revealed: Female Sexuality Redefined for the 21st Century, Volume One—Primates (Katarina Nolte, 2009).

85 one ape that is monogamous: Ryan and Jethá, Sex at Dawn.

86 Chimps, bonobos, and human males: Ibid.

86 The meadow voles: Sherrie Gruder-Adams and Lowell L. Getz, “Comparison of the Mating System and Paternal Behavior in Microtus Ochrogaster and M. Pennsylvanicus,” Journal of Mammalogy 66, no. 1 (1985): 165–67.

86 The vasopressin receptor: Thomas R. Insel et al., “Patterns of   Brain Vasopressin Receptor Distribution Associated with Social Organization in Microtine Rodents,” Journal of Neuroscience 14, no. 9 (1994): 5381–92.

86 When genes from the monogamous male prairie voles: Lim et al., “Ventral Striatopallidal Oxytocin and Vasopressin V1a Receptors,” 555–70.

86 Men who have a gene variant: Hasse Walum et al., “Genetic Variation in the Vasopressin Receptor 1a Gene (AVPR1A) Associates with Pair-Bonding Behavior in Humans,” 105, no. 37 (2008): 14153–56.

86 Married men and fathers: Sari M. van Anders and Neil V. Watson, “Relationship Status and Testosterone in North American Heterosexual and Non-Heterosexual Men and Women: Cross-sectional and Longitudinal Data,” Psychoneuroendocrinology 31, no. 6 (2006): 715–23.

86 Right after his child is born: Gray et al., “Marriage and Fatherhood,” 193–201.

86 Men who maintain multiple female partners: Alexandra Alvergne et al., “Variation in Testosterone Levels and Male Reproductive Effort: Insight from a Polygynous Human Population,” Hormones and Behavior 56, no. 5 (2009): 491–97.

87 married men with higher testosterone: Lee T. Gettler et al., “Do Testosterone Declines During the Transition to Marriage and Fatherhood Relate to Men’s Sexual Behavior? Evidence from the Philippines,” Hormones and Behavior 64, no. 5 (2013): 755–63.

87 men who cheat: Peter T. Ellison, “Social Relationships and Reproductive Ecology,” in Endocrinology of Social Relationships (Cambridge, MA: Harvard University Press, 2009), 54–73.

87 women rated men with lower voices: Jillian J. M. O’Connor et al., “Perceptions of Infidelity Risk Predict Women’s Preferences for Low Male Voice Pitch in Short-Term over Long-Term Relationship Contexts,” Personality and Individual Differences 56 (2014): 73–77.

87 “The search for the unfamiliar”: Meredith F. Small, Female Choices: Sexual Behavior of Female Primates (Ithaca, NY: Cornell University Press, 1993), 153.

87 Nature has bred philandering: Fisher, Anatomy of Love.

88 Research suggests that people who cheat: T. Orzeck and E. Lung, “Big-Five Personality Differences of Cheaters and Non-Cheaters,” Current Psychology 24 (2005): 274–86.

88 more easily bored: S. Hendrick and C. Hendrick, “Multidimensionality of Sexual Attitudes,” The Journal of Sex Research 23 (1987): 502–26.

88 Couples who spend all their time: Esther Perel, Mating in Captivity: Unlocking Erotic Intelligence (New York: Harper, 2007).

88 one partner will be clingier: Stan Tatkin, Wired for Love: How Understanding Your Partner’s Brain and Attachment Style Can Help You Defuse Conflict and Build a Secure Relationship (Oakland, CA: New Harbinger Publications, 2012).

89 Couples who spend weekly time: W. Bradford Wilcox and Jeffrey Dew, “The Date Night Opportunity: What Does Couple Time Tell Us About the Potential Value of Date Nights?” National Marriage Project, 2012, http://www.virginia.edu/marriageproject.

89 Spouses who share friends: P. R. Amato and S. J. Rogers, “A Longitudinal Study of Marital Problems and Subsequent Divorce,” Journal of Marriage and the Family 59 (1997): 612–24.

89 For couples with kids: Jeffrey Dew, “Has the Marital Time Cost of Parenting Changed Over Time?” Social Forces 88, no. 2 (2009): 519–41.

89 Nearly a third of marriages: Tammy Nelson, The New Monogamy: Redefining Your Relationship After Infidelity (Oakland: New Harbinger Publications, 2013).

89 Sometimes the discovery: Bruce Roscoe et al., “Dating Infidelity: Behaviors, Reasons and Consequences,” Adolescence 89 (1988) 35–43; Druckerman, Lust in Translation.

89 improve communication: Michael M. Olson et al., “Emotional Processes Following Disclosure of an Extramarital Affair,” Journal of Marital and Family Therapy 28, no. 4 (2002): 423–34.

89 quality of the partnership: Hansen, “Extradyadic Relations During Courtship,” 382–90.

90 One of you went outside: Solomon and Tatkin, Love and War in Intimate Relationships.

90 Sometimes people have sex: D. Easton and C. Liszt, The Ethical Slut: A Guide to Infinite Sexual Possibilities (Eugene: Greenery Press, 1997).

90 “couples who negotiate . . . long-term love”: Perel, Mating in Captivity, 179.

92 Dopamine injected into the male rat’s: F. Ferrari and D. Giuliani, “Sexual Attraction and Copulation in Male Rats: Effects of the Dopamine Agonist SND 919,” Pharmacology Biochemistry and Behavior 50, no. 1 (1995): 29–34.

92 horny rats that copulate: D. Wenkstern et al., “Dopamine Transmission Increases in the Nucleus Accumbens of Male Rats During Their First Exposure to Sexually Receptive Female Rats,” Brain Research 618, no. 1 (1993): 41–46.

92 excitation transfer: J. Bancroft et al., “The Relation Between Mood and Sexuality in Heterosexual Men,” Archives of Sexual Behavior 32 (2003): 217–30.

92 Regular exposure to male pheromones: Winnifred B. Cutler et al., “Sexual Behavior Frequency and Menstrual Cycle Length in Mature Premenopausal Women,” Psychoneuroendocrinology 4, no. 4 (1979): 297–309.

93 “almost all individuals”: Fisher, Why We Love.

93 Negativity is invisible abuse: Hendrix and Hunt, Making Marriage Simple.

94 Mirror, validate: Ibid.

94 we may be physiologically built: David G. Blanchflower, and Andrew J. Oswald, “Money, Sex and Happiness: An Empirical Study,” The Scandinavian Journal of Economics 106, no. 3 (2004): 393–415.

94 Cultivating and maintaining: D. Kahnman, “Objective Happiness,” in Well-Being: The Foundations of Hedonic Psychology, ed. Daniel Kahneman, Ed Diener, and Norbert Schwarz (New York: Russell Sage Foundation, 2003), 3–26.

Chapter Five: Motherhead

95 massive neuronal reorganization: Doidge, The Brain That Changes Itself.

95 neurons multiply at a rate: Craig Howard Kinsley, “The Neuroplastic Maternal Brain,” Hormones and Behavior 54, no. 1 (2008): 1–4; Cindy K. Barha and Liisa A. M. Galea, “Influence of Different Estrogens on Neuroplasticity and Cognition in the Hippocampus,” Biochimica et Biophysica Acta (BBA)—General Subjects 1800, no. 10 (2010): 1056–67.

95 “baby brain suck”: Carrie Cuttler et al., “Everyday Life Memory Deficits in Pregnant Women,” Canadian Journal of Experimental Psychology/Revue Canadienne de Psychologie Expérimentale 65, no. 1 (2011): 27; Charles M. Poser et al., “Benign Encephalopathy of Pregnancy Preliminary Clinical Observations,” Acta Neurologica Scandinavica 73, no. 1 (1986): 39–43; Peter M. Brindle et al., “Objective and Subjective Memory Impairment in Pregnancy,” Psychological Medicine 21, no. 03 (1991): 647–53.

96 Parental-induced neuroplasticity: Craig Kinsley and Kelly Lambert, “Reproduction-Induced Neuroplasticity: Natural Behavioral and Neuronal Alterations Associated with the Production and Care of Offspring,” Journal of Neuroendocrinology 20, no. 4 (2008a): 515–25.

96 The hormone responsible: Doidge, The Brain That Changes Itself.

96 During conception, oxytocin: G. Kunz et al., “Uterine Peristalsis During the Follicular Phase of the Menstrual Cycle: Effects of Estrogen, Antioestrogen and Oxytocin,” Human Reproduction Update 4, no. 5 (1998): 647–54.

96 During childbirth, oxytocin: Anna-Riitta Fuchs et al., “Oxytocin Receptors and Human Parturition: A Dual Role for Oxytocin in the Initiation of Labor,” Science 215, no. 4538 (1982): 1396–98.

96 In some experiments: Carsten De Dreu et al., “The Neuropeptide Oxytocin Regulates Parochial Altruism in Intergroup Conflict Among Humans,” Science 328, no. 5984 (2010): 1408–11.

96 Motherhood brings a whole new: A. Ferreira et al., “Role of Maternal Behavior on Aggression, Fear and Anxiety,” Physiology & Behavior 77, no. 2 (2002): 197–204.

96 Sometimes existing attachments: Walter J. Freeman, Neurodynamics: An Exploration in Mesoscopic Brain Dynamics (New York: Springer, 2000).

97 Though we’re starting later: Natalie Angier, “The Changing American Family,” New York Times, November 25, 2013.

97 The quality of eggs: Lewis Krey et al., “Fertility and Maternal Age,” Annals of the New York Academy of Sciences 943, no. 1 (2001): 26–33.

98 Fertility drugs: Linda Hammer Burns, “Psychiatric Aspects of Infertility and Infertility Treatments,” Psychiatric Clinics of North America 30, no. 4 (2007): 689–716; J. L. Blenner, “Clomiphene-Induced Mood Swings,” Journal of Obstetric, Gynecologic, & Neonatal Nursing 20, no. 4 (1991): 321–27; So-Hyun Choi et al., “Psychological Side-Effects of Clomiphene Citrate and Human Menopausal Gonadotrophin,” Journal of Psychosomatic Obstetrics & Gynecology 26, no. 2 (2005): 93–100.

98 Rare cases of psychosis: F. Siedentopf et al., “Clomiphene Citrate as a Possible Cause of a Psychotic Reaction During Infertility Treatment,” Human Reproduction 12, no. 4 (1997): 706–7.

98 mania: Rainer N. Persaud and Raymond W. Lam, “Manic Reaction After Induction of Ovulation with Gonadotropins,” American Journal of Psychiatry 155, no. 3 (1998): 447–48.

98 Nesting: J. Johnston, “The Nesting Instinct,” Midwifery Today with International Midwife 71 (2003): 36–37.

98 Gynecologists will sometimes: V. Hendrick et al., “Antidepressant Medications, Mood and Male Fertility,” Psychoneuroendocrinology 25, no. 1 (2000): 37–51.

98 melatonin tablets: M. Juszczak and M. Michalska. “The Effect of Melatonin on Prolactin, Luteinizing Hormone (LH), and Follicle-Stimulating Hormone (FSH) Synthesis and Secretion,” Postepy higieny i medycyny doswiadczalnej (online) 60 (2005): 431–38.

98 the high levels of stress: Elysia Poggi Davis et al., “Prenatal Exposure to Maternal Depression and Cortisol Influences Infant Temperament,” Journal of the American Academy of Child & Adolescent Psychiatry 46, no. 6 (2007): 737–46; R. L. Huot et al., “Negative Affect in Offspring of Depressed Mothers Is Predicted by Infant Cortisol Levels at 6 Months and Maternal Depression During Pregnancy, But Not Postpartum,” Annals of the New York Academy of Sciences 1032, no. 1 (2004): 234–36.

98 The risks are low but present: K. A. Yonkers et al., “The Management of Depression During Pregnancy: A Report from the American Psychiatric Association and the American College of Obstetricians and Gynecologists,” Obstetrics and Gynecology 114 (2009): 703–13; Rachel M. Hayes et al., “Maternal Antidepressant Use and Adverse Outcomes: A Cohort Study of 228,876 Pregnancies,” American Journal of Obstetrics and Gynecology 207, no. 1 (2012): 49.e1-49.e9.

98–99 link between SSRI exposure: Rebecca A. Harrington et al., “Serotonin Hypothesis of Autism: Implications for Selective Serotonin Reuptake Inhibitor Use During Pregnancy,” Autism Research 6, no. 3 (2013): 149–68.

99 another said it was twice as likely: Lisa A. Croen et al., “Antidepressant Use During Pregnancy and Childhood Autism Spectrum Disorders,” Archives of General Psychiatry 68, no. 11 (2011): 1104–12.

99 other studies don’t bear this out: Anders Hviid et al., “Use of Selective Serotonin Reuptake Inhibitors During Pregnancy and Risk of Autism,” New England Journal of Medicine 369, no. 25 (2013): 2406–15; Merete Juul Sørensen et al., “Antidepressant Exposure in Pregnancy and Risk of Autism Spectrum Disorders,” Clinical Epidemiology 5 (2013): 449.

99 women with bipolar disorder: Yonkers et al., “The Management of Depression During Pregnancy,” 703–13.

99 Rates of depression: Lori L. Altshuler et al., “An Update on Mood and Anxiety Disorders During Pregnancy and the Postpartum Period,” Primary Care Companion to the Journal of Clinical Psychiatry 2, no. 6 (2000): 217.

99 in women who are younger: Ibid.

100 Many women report the worst sleep: Kathryn A. Lee and Aaron B. Caughey, “Evaluating Insomnia During Pregnancy and Postpartum,” in Sleep Disorders in Women (Totowa, NJ: Humana Press, 2006), 185–98.

100 Insomnia comes: Jodi A. Mindell and Barry J. Jacobson, “Sleep Disturbances During Pregnancy,” Journal of Obstetric, Gynecologic, & Neonatal Nursing 29, no. 6 (2000): 590–97.

100 we’re given an epidural: Ellice Lieberman and Carol O’Donoghue, “Unintended Effects of Epidural Analgesia During Labor: A Systematic Review,” American Journal of Obstetrics and Gynecology 186, no. 5 (2002): S31–S68.

101 (Endocannabinoids): Osama M. H. Habayeb et al., “Plasma Levels of the Endocannabinoid Anandamide in Women—A Potential Role in Pregnancy Maintenance and Labor?” Journal of Clinical Endocrinology & Metabolism 89, no. 11 (2004): 5482–87.

101 Endocannabinoids: The endocannabinoid system is well represented in the reproductive tissues and is involved in ovulation and implantation as well.

101 peak during labor induction: V. Nallendran et al., “The Plasma Levels of the Endocannabinoid, Anandamide, Increase with the Induction of Labor,” BJOG: An International Journal of Obstetrics & Gynecology 117, no. 7 (2010): 863–69.

101 breast-fed babies: Dale L. Johnson et al., “Breast Feeding and Children’s Intelligence,” Psychological Reports 79, no. 3f (1996): 1179–85.

101 lower incidences of breast cancer: Polly A. Newcomb et al., “Lactation and a Reduced Risk of Premenopausal Breast Cancer,” New England Journal of Medicine 330, no. 2 (1994): 81–87.

101 ovarian cancer: Marta L. Gwinn et al., “Pregnancy, Breast Feeding, and Oral Contraceptives and the Risk of Epithelial Ovarian Cancer,” Journal of Clinical Epidemiology 43, no. 6 (1990):

559–68.

101 They also have lower: Elizabeth Sibolboro Mezzacappa, “Breastfeeding and Maternal Stress Response and Health.” Nutrition Reviews 62, no. 7 (2004): 261–68.

101 Oxytocin turns down: S. C. Gammie et al., “Role of Corticotropin Releasing Factor-Related Peptides in the Neural Regulation of Maternal Defense,” Neurobiology of the Parental Brain (San Diego, CA: Elsevier, 2008).

101 Breast milk has tryptophan: W. E. Heine, “The Significance of Tryptophan in Infant Nutrition,” Adv Exp Med Biol 467 (1999): 705–10.

102 stimulates endorphin production: T. Barrett et al., “Does Melatonin Modulate Beta-Endorphin, Corticosterone, and Pain Threshold?” Life Sciences 66, no. 6 (2000): 467–76.

102 endorphins called galattorphins: Ibid., Zanardo.

102 have higher endorphin levels: V. Zanardo et al., “Beta Endorphin Concentrations in Human Milk,” J Pediatr Gastroenterol Nutr 33, no. 2 (2001): 160–64; R. Franceschini et al., “Plasma Beta-Endorphin Concentrations During Suckling in Lactating Women,” Br J Obstet Gynaecol 96, no. 6 (1989): 711–13.

102 also contains cannabinoids: Timothy H. Marczylo et al., “A Solid-Phase Method for the Extraction and Measurement of Anandamide from Multiple Human Biomatrices,” Analytical Biochemistry 384, no. 1 (2009): 106–13.

102 Goat milk has: R. Mechoulam et al., “Endocannabinoids, Feeding and Suckling—from Our Perspective,” International Journal of Obesity 30 (2006): S24–S28.

102 human breast milk: V. Di Marzo et al., “Trick or Treat from Food Endocannabinoids?” Nature 396 (1998): 636–37; Florence Williams, Breasts: A Natural and Unnatural History (New York: W. W. Norton & Company, 2012).

102 cannabinoid receptors: Ester Fride, “The Endocannabinoid-CB1 Receptor System in Pre- and Postnatal Life,” European Journal of Pharmacology 500, no. 1 (2004): 289–97.

102 given to newborn mice: Ester Fride et al., “Critical Role of the Endogenous Cannabinoid System in Mouse Pup Suckling and Growth,” European Journal of Pharmacology 419, no. 2 (2001): 207–14.

102 babies may get fatter: Y. Le Strat and B. Le Foll, “Obesity and Cannabis Use: Results from 2 Representative National Surveys,” American Journal of Epidemiology 174, no. 8 (2011): 929.

102 Even though stoners: N. Rodondi et al., “Marijuana Use, Diet, Body Mass Index, and Cardiovascular Risk Factors (from the CARDIA Study),” American Journal of Cardiology 98, no. 4 (2006): 478–84.

102 Cannabinoids in breast milk: Williams, Breasts.

102 appreciable levels of pollutants: Ibid.

102 you burn about thirty calories: Linda S. Adair and Ernesto Pollitt, “Energy Balance During ­Pregnancy and Lactation,” Lancet 320, no. 8291 (1982): 219; F. Kramer et al., “Breast-Feeding Reduces Maternal Lower-Body Fat,” Journal of the American Dietetic Association 93, no. 4 (1993): 429–33.

102 breast milk into a bottle: Avent Isis gets my vote for best breast pump.

103 Cuddling and nurturing: Thomas R. Insel, “Oxytocin—a Neuropeptide for Affiliation: Evidence from ­Behavioral, Receptor Autoradiographic, and Comparative Studies,” Psychoneuroendocrinology 17, no. 1 (1992): 3–35.

103 cohabiting parents share: Ilanit Gordon et al., “Oxytocin and the Development of Parenting in Humans,” Biological Psychiatry 68, no. 4 (2010): 377–82.

103 his bond will be stronger: Linda F. Palmer, “The Chemistry of Attachment,” Attachment Parenting International News 5, no. 2 (2002).

103 Vasopressin is the biggest factor: Thomas R. Insel et al., “Oxytocin, Vasopressin, and the ­Neuroendocrine Basis of Pair Bond Formation,” in Vasopressin and Oxytocin (U.S.: Springer, 1998), 215–24.

103 Men have prolactin: Alison S. Fleming et al., “Testosterone and Prolactin Are Associated with Emotional Responses to Infant Cries in New Fathers,” Hormones and Behavior 42, no. 4 (2002): 399–413.

103 Monkeys reared without physical contact: John Bowlby, “Maternal Care and Mental Health,” Journal of Consulting Psychology 16, no. 3 (1952): 232.

103 their brain chemicals imbalanced: Maté, When the Body Says No.

103 In laboratory animals: Myron A. Hofer, “Physiological and Behavioral Processes in Early Maternal Deprivation,” Physiology, Emotion and Psychosomatic Illness, Elsevier (1972): 175–86.

103 Maternal care in infancy: Christian Caldji et al., “Maternal Care During Infancy Regulates the Development of Neural Systems Mediating the Expression of Fearfulness in the Rat,” PNAS 95, no. 9 (1998): 5335–40; Christian Caldji et al., “Variations in Maternal Care in Infancy Regulate the Development of Stress Reactivity,” Biological Psychiatry 48, no. 12 (2000): 1164–74.

103 disruption of attachment in infancy: Maté, When the Body Says No.

104 When we give our children: Daniel J. Siegel and Mary Hartzell, Parenting  from the Inside Out (New York: Penguin, 2003).

104 As many as 50 to 80 percent of women: Michael W. O’Hara, “Post-partum Blues, Depression, and Psychosis: A Review,” Journal of Psychosomatic Obstetrics & Gynecology 7, no. 3 (1987): 205–27.

105 But roughly 10 to 15 percent: Joanna L. Workman et al., “Endocrine Substrates of Cognitive and Affective Changes During Pregnancy and Postpartum,” Behavioral Neuroscience 126, no. 1 (2012): 54.

105 energy, appetite, sleep, and libido: Zachary N. Stowe and Charles B. Nemeroff, “Women at Risk for ­Postpartum-Onset Major Depression,” American Journal of Obstetrics and Gynecology 173, no. 2 (1995): 639–45.

105 postpartum psychosis: O’Hara, “Post-partum Blues, Depression,” 205–27.

105 Prolactin can make us: Maureen W. Groer and Katherine Morgan, “Immune, Health and Endocrine Characteristics of Depressed Postpartum Mothers,” Psychoneuroendocrinology 32, no. 2 (2007): 133–39.

105 the postpartum blues: Michael W. O’Hara et al., “Prospective Study of Postpartum Blues: Biologic and Psychosocial Factors,” Archives of General Psychiatry 48, no. 9 (1991): 801.

105 a quick drop-off of estrogen: O’Hara, “Post-partum Blues, Depression,” 205–27.

105 The peak time for postpartum depression: Victor J. M. Pop et al., “Prevalence of Post Partum ­Depression: or Is It Post-Puerperium Depression?” Acta obstetricia et gynecologica Scandinavica 72, no. 5 (1993): 354–58.

106 Breast-feeding reliably reduces: Cristina Borra, Maria Iacovou, and Almudena Sevilla, “New Evidence on Breastfeeding and Postpartum Depression: The Importance of Understanding Women’s Intentions,” Maternal and Child Health Journal (2014): 1–11.

106 if your baby is colicky: Jenny S. Radesky et al., “Inconsolable Infant Crying and Maternal Post­partum Depressive Symptoms,” Pediatrics 131, no. 6 (2013): e1857–e1864.

106 A history of a previous depression: Miki Bloch et al., “Risk Factors Associated with the Development of Postpartum Mood Disorders,” Journal of Affective Disorders 88, no. 1 (2005): 9–18.

106 The rational frontal lobes: Sandra Aamodt and Sam Wang, Welcome to Your Child’s Brain: How the Mind Grows, from Birth to University (London: Oneworld Publications, 2012).

106 for your teenage daughter: Sil Reynolds and Eliza Reynolds, Mothering and Daughtering: Keeping Your Bond Strong Through the Teenage Years (Boulder, CO: Sounds True, 2013).

107 Mothering is as much about: Ibid.

107 Since the 1970s: Angier, “The Changing American Family,” New York Times.

108 Three-quarters of women today: Ibid.; Pew Research Center analysis of 2011 American Community ­Survey.

108 40 percent of us: Ibid., Angier.

108 They learn from their peers: Gordon Neufeld and Gabor Maté, Hold On to Your Kids: Why Parents Need to Matter More Than Peers (Toronto: Vintage, 2013).

108 “cooperative breeders”: Sarah Blaffer Hrdy, “Mothers and Others,” Natural History 110, no. 4 (2001): 50–62.

108 In tribal societies: Ryan and Jethá, Sex at Dawn.

108 “inappropriate for our species”: Ibid., 109

109 In a survey of married women: Brooke Showell, “The State of Married Sex,” iVillage.com, May 8, 2010.

109 women in early pregnancy: Kay Mordecai Robson et al., “Maternal Sexuality During First Pregnancy and After Childbirth,” BJOG: An International Journal of Obstetrics & Gynecology 88, no. 9 (1981): 882–89; A. Don Solberg et al., “Sexual Behavior in Pregnancy,” in Handbook of Sex Therapy (U.S.: Springer, 1978), 361–71.

109–110 marital satisfaction plummets: Carolyn Pape Cowan and Philip A. Cowan, When Partners Become Parents: The Big Life Change for Couples (Hillsdale, NJ: Lawrence Erlbaum Associates, 2000).

110 “the quality of the mother role”: Margaret A. De Judicibus and Marita P. McCabe, “Psychological Factors and the Sexuality of Pregnant and Postpartum Women,” Journal of Sex Research 39, no. 2 (2002): 94–103.

110 The first three months postpartum: Virginia L. Larsen, “Stresses of the Childbearing Year,” American Journal of Public Health and the Nations Health 56, no. 1 (1966): 32–36.

110 a few reasons for lackluster libido: Berman,and Berman, For Women Only.

110 Having little kids climbing all over you: Ibid.

110 married women have lower testosterone: Emily S. Barrett et al., “Marriage and Motherhood Are Associated with Lower Testosterone Concentrations in Women,” Hormones and Behavior 63, no. 1 (2013): 72–79.

111 Your children end up being: Perel, Mating in Captivity.

111 “virtual annihilation of the self”: Sheila Kitzinger, Ourselves as Mothers: The Universal Experience of Motherhood (Reading, MA: Addison-Wesley, 1995).

111 Our frustration about: John Mordechai Gottman and Nan Silver, The Seven Principles for Making Marriage Work (New York: Random House, 1999).

111 And until nonsexual issues: Winks and Semans, Sexy Mamas.

112 more men than women complain: Patricia Love and Jo Robinson, Hot Monogamy: Essential Steps to More Passionate, Intimate Lovemaking (Dutton, 1994).

112 For men, sex can be the only way: Perel, Mating in Captivity.

112 A desire discrepancy: Love and Robinson, Hot Monogamy.

112 In an iVillage survey: Showell, The State of Married Sex.

113 The book Sexy Mamas recommends: winks and semans, Sexy Mamas.

114 Sometimes what’s hot is: Ibid.

115 “authentic eroticism”: Ibid., 191

Chapter Six: Perimenopause: The Storm Before the Calm

117 The average age for menopause: Berman and Berman, For Women Only.

118 Nearly a quarter of women: Jennifer Senior, All Joy and No Fun: The Paradox of Modern Parenthood (New York: HarperCollins, 2014).

118 one Gallup poll from 1998: Jim Duffy, “Lifting the Fog,” Hopkins Medicine, October 1, 2013, 31–37.

119 Complaints during this stretch: Sara Gottfried, The Hormone Cure: Reclaim Balance, Sleep, Sex Drive and Vitality Naturally with the Gottfried Protocol (New York: Simon and Schuster, 2013); Berman and Berman, For Women Only.

119 three-quarters of women: Laura E. Corio, The Change Before the Change (New York: Bantam, 2000).

119 Hot flashes affect 80 percent of women: Ibid.

119 last between one and five minutes: Ellen W. Freeman et al., “Temporal Associations of Hot Flashes and Depression in the Transition to Menopause,” Menopause 16, no. 4 (2009): 728.

119 Sudden dips in estrogen levels: D. R. Meldrum et al., “Pituitary Hormones During the Menopausal Hot Flash,” Obstetrics and Gynecology 64, no. 6 (1984): 752–56.

120 The closer you get toward menopause Mary G. Metcalf, “Incidence of Ovulatory Cycles in Women ­Approaching the Menopause,” Journal of Biosocial Science 11, no. 1 (1979): 39–48.

121 A menopausal woman has 5 percent: Steven F. Hotze, Hormones, Health, and Happiness (Houston, TX: Forrest Publishing, 2005).

121 This means estrogen dominance: Gottfried, Hormone Cure.

121 Estrogen promotes fat storage: Hotze, Hormones, Health, and Happiness.

121 Add to this the xenoestrogens: Ibid.

121 Unopposed estrogen: Corio, The Change Before the Change.

121 Estrogen dominance is gone: Christiane Northrup, The Wisdom of Menopause, rev. ed. (Hay House, Inc., 2012).

122 belly and back fat: The hippy gynoid shape is normal in 80 percent of premenopausal women, but as the years tick by, more of us turn from pear-shaped to apple-shaped (called android), chipping that number down to 50 percent of perimenopausal women, and then to 40 percent of postmenopausal women.

122 hippy synoid shape: Corio, The Change Before the Change.

122 Your risk for diabetes rises: Rebecca C. Thurston et al., “Vasomotor Symptoms and Insulin Resistance in the Study of Women’s Health Across the Nation,” Journal of Clinical Endocrinology & Metabolism 97, no. 10 (2012): 3487–94.

122 So can stress: Stress causes the release of cortisol from the adrenal glands, which sit atop the kidneys. Cortisol counteracts insulin, causing higher blood sugar levels. It also stimulates sugar production in the liver, called gluconeogenesis, and stops the production of a transporter (called GLUT4) that sugar needs to get into the cell. All this excess glucose that isn’t burned as energy or stored for later use in the liver gets stored as belly fat.

122 increase in abdominal fat: André Tchernof et al., “Menopause, Central Body Fatness, and Insulin Resistance: Effects of Hormone-Replacement Therapy,” Coronary Artery Disease 9, no. 8 (1998): 503–12.

122 Progesterone can help with weight loss: Hotze, Hormones, Health, and Happiness.

122 If you don’t ovulate: Corio, The Change Before the Change.

122 high estrogen levels signal the liver: Hotze, Hormones, Health, and Happiness.

122 free thyroid hormone: Pregnancy, birth control pills, and estrogen supplementation can further increase the protein that gobbles up free thyroid hormone.

123 An underactive thyroid: Gottfried, Hormone Cure.

123 Fifty-year-old women produce: Hotze, Hormones, Health, and Happiness.

123 Rats that have their ovaries removed: Lori Asarian and Nori Geary, “Modulation of Appetite by Gonadal Steroid Hormones,” Philosophical Transactions of the Royal Society B: Biological Sciences 361, no. 1471 (2006): 1251–63.

123 one of the first symptoms: Freeman et al., “Temporal Associations of Hot Flashes and Depression,” 728.

124 Your risk of depression: E. W. Freeman et al., “Hormones and Menopausal Status as Predictors of Depression in Women in Transition to Menopause,” Archives of General Psychiatry 61 (2004): 62–70.

124 The prevalence of depression: “QuickStats: Prevalence of Current Depression Among Persons Aged 12 Years, by Age Group and Sex—United States, National Health and Nutrition Examination Survey, 2007–2010,” Morbidity and Mortality Weekly Report (MMWR) 60, no. 51 (2012): 1747.

124 When you remove a female rat’s ovaries: Erika Estrada-Camarena et al., “Antidepressant-like Effect of Different Estrogenic Compounds in the Forced Swimming Test,” Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology 28, no. 5 (2003): 830–38.

124 Lower estrogen levels: Zenab Amin et al., “Effect of Estrogen-Serotonin Interactions on Mood and Cognition,” Behavioral and Cognitive Neuroscience Reviews 4, no. 1 (2005): 43–58.

124 overall serotonin activity: Estrogen increases the expression of the gene for the enzyme that makes serotonin, and it also directly increases serotonin activity. If you want a sense of how estrogen and progesterone work as opposites, consider this: while estrogen creates high levels of serotonin by blocking its breakdown by the enzyme MAO, high progesterone levels increase MAO activity, thus lowering serotonin levels. High progesterone also inhibits testosterone’s mood-­elevating effects, which is why in the second half of your cycle, when progesterone dominates, you can feel depressed, sedated, and lackadaisical.

124 major depressions need to be treated: M. F. Morrison et al., “Lack of Efficacy of Estradiol for Depression in Post-Menopausal Women: A Randomized, Controlled Trial,” Biological Psychiatry 55 (2004): 406–12; Jennifer L. Payne et al., “A Reproductive Subtype of Depression: Conceptualizing Models and Moving Toward Etiology,” Harvard Review of Psychiatry 17, no. 2 (2009): 72–86.

124 High estrogen: Zenab Amin et al., “The Interaction of Neuroactive Steroids and GABA in the Development of Neuropsychiatric Disorders in Women,” Pharmacology Biochemistry and Behavior 84, no. 4 (2006): 635–43.

124 When the brain’s hormone control center: Corio, The Change Before the Change.

125 Women experience insomnia more than men: Ibid.

125 when cortisol levels drop: Theresa M. Buckley and Alan F. Schatzberg, “On the Interactions of the Hypothalamic-Pituitary-Adrenal (HPA) Axis and Sleep: Normal HPA Axis Activity and Circadian Rhythm, Exemplary Sleep Disorders,” Journal of Clinical Endocrinology & Metabolism 90, no. 5 (2005): 3106–14.

125 restless leg syndrome: Leg spasms occur in 40 percent of perimenopausal women, likely due to these low magnesium levels.

125 Estrogen dominance exacerbates: Hotze, Hormones, Health, and Happiness.

125 Estrogen is involved in: Bruce S. McEwen and Stephen E. Alves, “Estrogen Actions in the Central Nervous System 1.” Endocrine Reviews 20, no. 3 (1999): 279–307.

126 memory and concentration: Nouns are the first to go; people’s names or the title of the movie you saw last night will escape you when your estrogen levels dip. Verbal memory seems the specific domain of estrogen, though some menopausal women report less fine-motor coordination and longer reaction times.

126 Giving women estrogen can: Barbara B. Sherwin and Susana Phillips, “Estrogen and Cognitive Functioning in Surgically Menopausal Women,” Annals of the New York Academy of Sciences 592, no. 1 (1990): 474–75; Barbara B. Sherwin, “Estrogen and Cognitive Functioning in Women,” Endocrine Reviews 24, no. 2 (2003): 133–51.

126 vigilance, reasoning: E. S. LeBlanc et al., “Hormone Replacement Therapy and Cognition: Systematic Review and Metaanalysis,” JAMA 285 (2001): 1489–99.

126 Testosterone is essential for learning: Elizabeth Barrett-Connor and Deborah Goodman-Gruen, “Cognitive Function and Endogenous Sex Hormones in Older Women,” Journal of the American Geriatrics Society (1999); Jeri S. Janowsky, “Thinking with Your Gonads: Testosterone and Cognition,” Trends in Cognitive Sciences 10, no. 2 (2006): 77–82.

126 Testosterone can directly influence: David R. Rubinow and Peter J. Schmidt, “Androgens, Brain, and Behavior,” American Journal of Psychiatry 153, no. 8 (1996): 974–84.

126 Postmenopausal women score better: Barbara B. Sherwin, “Estrogen and/or Androgen Replacement Therapy and Cognitive Functioning in Surgically Menopausal Women,” Psychoneuroendocrinology 13, no. 4 (1988): 345–57.

126 Postmenopausal women who take estrogen: Peter P. Zandi et al., “Hormone Replacement Therapy and Incidence of Alzheimer Disease in Older Women: The Cache County Study,” JAMA 288, no. 17 (2002): 2123–29.

126 Testosterone also reduces: Gunnar K. Gouras et al., “Testosterone Reduces Neuronal Secretion of Alzheimer’s B-Amyloid Peptides,” PNAS 97, no. 3 (2000): 1202–5.

126 plays a neuroprotective role: Janowsky, “Thinking with Your Gonads,” 77–82.

126 estrogen increases BDNF levels: V. Luine and M. Frankfurt, “Interactions Between Estradiol, BDNF and Dendritic Spines in Promoting Memory,” Neuroscience 239 (2013): 34–45.

127 that number drops to 38 percent: Joey Sprague and David Quadagno, “Gender and Sexual ­Motivation: An Exploration of Two Assumptions,” Journal of Psychology & Human Sexuality 2, no. 1 (1989): 57–76.

127 minus the sexual attraction: Lori Gottlieb, “Does a More Equal Marriage Mean Less Sex?” New York Times, February 6, 2014.

127 sexy thoughts can trigger: Katherine L. Goldey and Sari M. van Anders, “Sexy Thoughts: Effects of Sexual Cognitions on Testosterone, Cortisol, and Arousal in Women,” Hormones and Behavior 59, no. 5 (2011): 754–64.

127 Sexual function may rely more: Lorraine Dennerstein et al., “The Relative Effects of Hormones and Relationship Factors on Sexual Function of Women Through the Natural Menopausal Transition,” Fertility and Sterility 84, no. 1 (2005): 174–80.

128 Younger eggs are more likely: D. T. Armstrong, “Effects of Maternal Age on Oocyte Developmental Competence,” Theriogenology 55, no. 6 (2001): 1303–22.

128 The risk of autism and schizophrenia rises: Abraham Reichenberg et al., “Advancing Paternal Age and Autism,” Archives of General Psychiatry 63, no. 9 (2006): 1026–32; Dolores Malaspina et al., “Advancing Paternal Age and the Risk of Schizophrenia,” Archives of General Psychiatry 58, no. 4 (2001): 361–67.

128 Men’s testosterone begins to wane: S. M. Harman et al., “Longitudinal Effects of Aging on Serum Total and Free Testosterone Levels in Healthy Men,” Baltimore Longitudinal Study of Aging, J Clin Endocrinol Metabol 86 (2001): 724–31.

128 older men end up having twice as much estrogen: Joel S. Finkelstein et al., “Gonadal Steroids and Body Composition, Strength, and Sexual Function in Men,” New England Journal of Medicine 369, no. 11 (2013): 1011–22.

128 testosterone levels: Two androgens, testosterone and androstenedione, are still made in the ovaries up to five years after menopause.

128 testosterone dominance: Uwe D. Rohr, “The Impact of Testosterone Imbalance on Depression and Women’s Health,” Maturitas 41 (2002): 25–46.

128 A steep decline occurs: Rohr, “The Impact of Testosterone Imbalance,” 25–46.

128 When estrogen levels are high: Hotze, Hormones, Health, and Happiness.

129 libido bump: Tibolone, a medicine that raises free testosterone and estrogen level, but, more important, lowers SHBG levels, improves mood and libido in menopausal women.

129 High testosterone levels in women correlate positively: Sari M. van Anders, “Testosterone and Sexual Desire in Healthy Women and Men,” Archives of Sexual Behavior 41, no. 6 (2012): 1471–84.

129 whether the levels are too low: Rebecca Goldstat et al., “Transdermal Testosterone Therapy Improves Well-Being, Mood, and Sexual Function in Premenopausal Women,” Menopause 10, no. 5 (2003): 390–98.

129 or too high: Joyce T. Bromberger et al., “Longitudinal Change in Reproductive Hormones and Depressive Symptoms Across the Menopausal Transition: Results from the Study of Women’s Health Across the Nation (SWAN),” Archives of General Psychiatry 67, no. 6 (2010): 598–607.

129 15 to 20 percent of American couples: Bob Berkowitz and Susan Yager-Berkowitz, He’s Just Not Up for It Anymore: Why Men Stop Having Sex, and What You Can Do About It (New York: HarperCollins, 2007).

130 Lack of interest in sex: Edward O. Laumann et al., “Sexual Dysfunction in the United States: Prevalence and Predictors,” JAMA 281, no. 6 (1999): 537–44; Alan Riley and Elizabeth Riley, “Controlled Studies on Women Presenting with Sexual Drive Disorder: I. Endocrine Status,” Journal of Sex & Marital Therapy 26, no. 3 (2000): 269–83.

130 A badly functioning thyroid: Berman and Berman, For Women Only.

130 When magnesium levels are depleted: Hotze, Hormones, Health, and Happiness.

130 in the later stages of the transition: Brian W. Somerville, “The Role of Estradiol Withdrawal in the Etiology of Menstrual Migraine,” Neurology 22, no. 4 (1972): 355–55.

130 migraines can result: Low estrogen and low magnesium levels are also the cause of premenstrual migraines during PMS.

130 synthetic progestins such as Provera: Ann E. MacGregor, “Contraception and Headache,” Headache: The Journal of Head and Face Pain 53, no. 2 (2013): 247–76.

130 Natural, bioidentical progesterones: Corio, The Change Before the Change.

130 decreased blood flow to the vagina: Berman and Berman, For Women Only.

131 orgasms become weaker: Corio, The Change Before the Change.

131 Nipple sensation wanes: Berman and Berman, For Women Only.

131 may have more anovulatory cycles: Britt-Marie Landgren et al., “Menopause Transition: Annual Changes in Serum Hormonal Patterns over the Menstrual Cycle in Women During a Nine-Year Period Prior to Menopause,” Journal of Clinical Endocrinology & Metabolism 89, no. 6 (2004): 2763–69; Henry G. Burger et al., “Cycle and Hormone Changes During Perimenopause: The Key Role of Ovarian Function,” Menopause 15, no. 4 (2008): 603–12.

131 Testosterone levels begin to wane: A. Guay et al., “Serum Androgen Levels in Healthy Premenopausal Women with and without Sexual Dysfunction: Part A. Serum Androgen Levels in Women Aged 20–49 Years with No Complaints of Sexual Dysfunction,” International Journal of Impotence Research 16, no. 2 (2004): 112–20.

131 Testosterone supplementation: Corio, The Change Before the Change.

131 A study of menopausal women: R. D. Gambrell Jr. and R. B. Greenblatt, “Hormone Therapy for the Menopause,” Geriatrics 36, no. 7 (1981): 53–61.

131 “If women care about their bones”: Irwin Goldstein (director, Sexual Medicine, Alvarado Hospital, San Diego, CA), interview conducted by phone, June 4, 2014.

131 Testosterone supplementation reduces osteoporosis: Susan R. Davis et al., “Testosterone Enhances Estradiol’s Effects on Postmenopausal Bone Density and Sexuality,” Maturitas 21, no. 3 (1995): 227–36.

131 estrogen’s effects: In women with higher SHBG taking oral estrogens, muscle mass is reduced.

131 increases muscle mass: S. Bhasin et al., “Proof of the Effect of Testosterone on Skeletal Muscle,” Journal of Endocrinology 170, no. 1 (2001): 27–38.

132 Ditch the oral contraceptives: Peter R. Casson et al., “Effect of Postmenopausal Estrogen Replacement on Circulating Androgens,” Obstetrics & Gynecology 90, no. 6 (1997): 995–98.

132 synthetic progesterones drive down: N. Van der Vange et al., “Effects of Seven Low-Dose Combined Oral Contraceptives on Sex Hormone Binding Globulin, Corticosteroid Binding Globulin, Total and Free Testosterone,” Contraception 41, no. 4 (1990): 345–52.

132 Drinking more leads to more conversion: Judith S. Gavaler and David H. Thiel, “The Association Between Moderate Alcoholic Beverage Consumption and Serum Estradiol and Testosterone Levels in Normal Postmenopausal Women: Relationship to the Literature,” Alcoholism: Clinical and Experimental Research 16, no. 1 (1992): 87–92.

132 the xenoestrogens in plastics: Hotze, Hormones, Health, and Happiness.

132 Vaginal atrophy: D. W. Sturdee and N. Panay, “Recommendations for the Management of Postmenopausal Vaginal Atrophy,” Climacteric 13, no. 6 (2010): 509–22.

132 “senile vagina”: Sandra Leiblum et al., “Vaginal Atrophy in the Postmenopausal Woman: The Importance of Sexual Activity and Hormones,” JAMA 249, no. 16 (1983): 2195–98.

133 vaginal itching, dryness, and burning: Corio, The Change Before the Change.

133 alterations in the vaginal pH: Berman and Berman, For Women Only.

133 Regular sex may help to maintain: Winnifred B. Cutler et al., “Sexual Behavior Frequency and Menstrual Cycle Length in Mature Premenopausal Women,” Psychoneuroendocrinology 4, no. 4 (1979): 297–309.

133 If lubrication is a problem: Berman and Berman, For Women Only.

133 Vaginal estrogen is superior: Corio, The Change Before the Change.

133 Local hormone treatment: Sturdee and Panay, “Recommendations for the Management of Postmenopausal Vaginal Atrophy,” 509–22.

133 sex becomes more goal oriented: Berman and Berman, For Women Only.

134 Viagra did help them: Ibid.

134 VENIS (very erotic, noninsertive sex): Ibid.

135 estrogen lowers the risk for diabetes: Youhua Xu et al., “Combined Estrogen Replacement Therapy on Metabolic Control in Postmenopausal Women with Diabetes Mellitus,” The Kaohsiung Journal of Medical Sciences 30, no. 7 (2014): 350–61.

135 HRT attenuates: A. O. Mueck, “Postmenopausal Hormone Replacement Therapy and Cardiovascular ­Disease: The Value of Transdermal Estradiol and Micronized Progesterone,” Climacteric 15, no. S1 (2012): 11–17.

135 normalize weight and appetite: Gail A. Greendale et al., “Symptom Relief and Side Effects of Postmenopausal Hormones: Results from the Postmenopausal Estrogen/Progestin Interventions Trial,” Obstetrics & Gynecology 92, no. 6 (1998): 982–88.

135 biodentical hormones: Bioidentical products are derived from plant hormones. Soybeans and Mexican wild yams contain diosgenin, which is converted into progesterone in a lab. It can be further converted into estrogen. One caveat: bioequivalent is not bioidentical. Equivalence has to do with potency only, and is a marketing strategy meant to confuse the consumer.

135 Provera and other synthetic progestins: Corio, The Change Before the Change.

135 Synthetic hormones can also deplete: Hotze, Hormones, Health, and Happiness.

135 Pills get broken down by the liver: Marinka S. Post et al., “Effect of Oral and Transdermal Estrogen Replacement Therapy on Hemostatic Variables Associated with Venous Thrombosis: A Randomized, Placebo-Controlled Study in Postmenopausal Women,” Arteriosclerosis, Thrombosis, and Vascular Biology 23, no. 6 (2003): 1116–21.

135 For testosterone supplementation: Hotze, Hormones, Health, and Happiness.

136 The Women’s Health Initiative: Ellen C. G. Grant, “Hormone Replacement Therapy and Risk of Breast Cancer,” JAMA 287, no. 18 (2002): 2360–61.

136 “million women study”: V. Beral et al., “Evidence from Randomized Trials on the Long-Term Effects of Hormone Replacement Therapy,” Lancet 360 (2002): 942–44.

136 women who started the hormones within months: Rowan T. Chlebowski et al., “Estrogen Plus Progestin and Breast Cancer Incidence and Mortality in the Women’s Health Initiative Observational Study,” Journal of the National Cancer Institute 105, no. 8 (2013): 526–35.

136 If a woman has her: Ronald K. Ross, et al.,”Effect of Hormone Replacement Therapy on Breast Cancer Risk: Estrogen Versus Estrogen Plus Progestin,” Journal of the National Cancer Institute 92, no. 4 (2000): 328–32; Catherine Schairer et al., “Menopausal Estrogen and Estrogen-Progestin Replacement Therapy and Breast Cancer Risk,” JAMA 283, no. 4 (2000): 485–91.

136 A study of infertile women: Linda D. Cowan et al., “Breast Cancer Incidence in Women with a History of Progesterone Deficiency,” American Journal of Epidemiology 114, no. 2 (1981): 209–17.

137 women have opted: Within a year of its publication, the number of prescriptions for Premarin and Prempro dropped to half of what they were. The good news is that large drops in breast cancer diagnoses followed suit over the next several years.

138 Procter & Gamble invested millions: Lila Nachtigall et al., “Safety and Tolerability of Testosterone Patch Therapy for Up to 4 Years in Surgically Menopausal Women Receiving Oral or Transdermal Estrogen,” Gynecological Endocrinology 27, no. 1 (2011): 39–48.

138 Obesity increases your risk: A. J. Hartz et al., “The Association of Obesity with Infertility and Related Menstural Abnormalities in Women,” International Journal of Obesity 3, no. 1 (1978): 57–73.

138 and hot flashes: Lisa Gallicchio et al., “Body Mass, Estrogen Levels, and Hot Flashes in Midlife Women,” American Journal of Obstetrics and Gynecology 193, no. 4 (2005): 1353–60.

138 Yoga and Pilates can help improve: T. Ivarsson et al., “Physical Exercise and Vasomotor Symptoms in Postmenopausal Women,” Maturitas 29 (1998): 139–46; Corio, The Change Before the Change.

138 Exercise . . . helps to make you horny: Tierney Ahrold Lorenz and Cindy May Meston, “Exercise Improves Sexual Function in Women Taking Antidepressants: Results from a Randomized Crossover Trial,” Depression and Anxiety 99 (2013):1–8.

139 a healthy activity that you do: Berman and Berman, For Women Only.

139 Having sex may help you: Michael F. Roizen and Elizabeth Anne Stephenson, Realage: Are You As Young As You Can Be? (New York: Cliff Street Books, 1999).

139 there is a correlation between orgasms: George Davey Smith et al., “Sex and Death: Are They Related? Findings from the Caerphilly Cohort Study,” British Medical Journal 315, no. 7123 (1997): 1641–44.

139 Vitamin D is crucial: Keiko Kinuta et al., “Vitamin D Is an Important Factor in Estrogen Biosynthesis of Both Female and Male Gonads.” Endocrinology 141, no. 4 (2000): 1317–24.

139 Soy milk has components: David T. Zava et al., “Estrogen and Progestin Bioactivity of Foods, Herbs, and Spices,” Experimental Biology and Medicine 217, no. 3 (1998): 369–78.

139 If you’re estrogen dominant: Berman and Berman, For Women Only.

139 The highest-binding herbs for progesterone-like: Zava et al., “Estrogen and Progestin Bioactivity of Foods,” 369–78.

139 one study found that it worked even better: G. Warnecke, “Influencing of Menopausal Complaints with a Phytodrug: Successful Therapy with Cimicifuga Monoextract,” Medizinische Welt 36 (1985): 871–74.

139 Pine bark extract: S. Errichi et al., “Supplementation with Pycnogenol® Improves Signs and Symptoms of Menopausal Transition,” Panminerva Medica 53, no. 3, suppl 1 (2011): 65–70; Han-Ming Yang et al., “A Randomised, Double-Blind, Placebo-Controlled Trial on the Effect of Pycnogenol® on Tte Climacteric Syndrome in Peri-Menopausal Women,” Acta Obstetricia Et Gynecologica Scandinavica 86, no. 8 (2007): 978–85.

139 Then there’s maca: H. O. Meissner et al., “Therapeutic Effects of Pre-Gelatinized Maca (Lepidium peruvianum Chacon) Used as a Non-Hormonal Alternative to HRT in Perimenopausal Women—Clinical Pilot Study,” IJBS 2, no. 2 (2006): 143; Julius Goepp, “A New Way to Manage Menopause Regain Hormonal Balance with a Cutting-edge Adaptogen,” Reprod Biol Endocrinol 3 (2005): 16; Nicole A. Brooks et al., “Beneficial Effects of Lepidium Meyenii (Maca) on Psychological Symptoms and Measures of Sexual Dysfunction in Postmenopausal Women Are Not Related to Estrogen or Androgen Content,” Menopause 15, no. 6 (2008): 1157–62.

140 well tolerated and may also be used: Christina M. Dording et al., “A Double-Blind, Randomized, Pilot Dose-Finding Study of Maca Root (L. Meyenii) for the Management of SSRI-Induced Sexual Dysfunction,” CNS Neuroscience & Therapeutics 14, no. 3 (2008): 182–91.

140 maca works its wonders without changing: Yali Wang et al., “Maca: An Andean Crop with Multi-­Pharmacological Functions,” Food Research International 40, no. 7 (2007): 783–92.

140 protect against brain damage: Alejandro Pino-Figueroa et al., “Mechanism of Action of Lepidium Meyenii (Maca): An Explanation for Its Neuroprotective Activity,” American Journal of Neuroprotection and Neuroregeneration 3, no. 1 (2011): 87–92.

140 Chasteberry, also known as vitex: Jianghua Liu et al., “Evaluation of Estrogenic Activity of Plant Extracts for the Potential Treatment of Menopausal Symptoms,” Journal of Agricultural and Food Chemistry 49, no. 5 (2001): 2472–79; M. Blumenthal, The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines (Austin, TX: American Botanical Council, 1998).

140 good for PMS: For more on using herbs for perimenopause, please see WomenToWomen.com.

140 compounds in cannabis: Kazuhito Watanabe et al., “Marijuana Extracts Possess the Effects Like the Endocrine Disrupting Chemicals,” Toxicology 206, no. 3 (2005): 471–78.

140 a variety of perimenopausal complaints: H. Diana van Die, “Herbal Medicine and Menopause: An Historical Perspective,” Australian Journal of Medical Herbalism 22, no. 4 (2010); Ethan Russo, “Cannabis Treatments in Obstetrics and Gynecology: A Historical Review,” Journal of Cannabis Therapeutics 2, no. 3–4 (2002): 5–35.

140 Cannabis increases luteinizing hormone levels: J. H. Mendelson et al., “Acute Effects of Marijuana on Luteinizing Hormone in Menopausal Women,” Pharmaco. Biochem Behav 23 (1985): 765.

140 Hemp seeds added to the diet of rats: A. Saberivand et al., “The Effects of Cannabis Sativa L. Seed (Hempseed) in the Ovariectomized Rat Model of Menopause,” Methods Find Exp Clin Pharmacol 32, no. 7 (2010): 467–73.

140 Cannabidiol (CBD), the component of cannabis: M. A. Sauer et al., “Marijuana: Interaction with the Estrogen Receptor,” J Pharmacol Exp Ther 224, no. 2 (1983): 404–7.

141 there are cannabinoid receptors: Aymen I. Idris et al., “Regulation of Bone Mass, Bone Loss and Osteoclast Activity by Cannabinoid Receptors,” Nature Medicine 11, no. 7 (2005): 774–79; Orr Ofek et al., “Peripheral Cannabinoid Receptor, CB2, Regulates Bone Mass,” PNAS 103, no. 3 (2006): 696–701.

141 Animal studies show that a synthetic CB2 agonist: Idris et al., “Regulation of Bone Mass,”; Antonia Sophocleous et al., “The Type 2 Cannabinoid Receptor Regulates Bone Mass and Ovariectomy-Induced Bone Loss by Affecting Osteoblast Differentiation and Bone Formation,” Endocrinology 152, no. 6 (2011): 2141–49.

141 people who have a genetic problem: Itai Bab et al., “Cannabinoids and the Skeleton: From Marijuana to Reversal of Bone Loss,” Annals of Medicine 41, no. 8 (2009): 560–67.

141 a third of our lives being postmenopausal: Duffy, “Lifting the Fog,” 31–37.

142 delineated downtime: Perhaps the new or full moon can serve as a reminder of spiritual growth and rebirth, of honoring the divine feminine.

142 our version of the midlife crisis: Ibid.

143 The majority of divorces in America: Xenia P. Montenegro, The Divorce Experience: A Study of Divorce at Midlife and Beyond Conducted for AARP The Magazine, AARP, Knowledge Management, National Member Research, 2004.

143 wrote about her experience in Vital Aging: Sara Wolff, Vital Aging: Seven Years of Building Community and Enhancing Health (Amherst, MA: Levelers Press, 2010).

Chapter Seven: Inflammation, The Key to Everything

148 Chronic stressors: Borja García-Bueno et al., “Stress as a Neuroinflammatory Condition in Brain: Damaging and Protective Mechanisms,” Neuroscience & Biobehavioral Reviews 32, no. 6 (2008): 1136–51.

149 Chronic stress can precede: Maté, When the Body Says No; K. S. Kendler and L. M. Karkowski, “Causal relationship Between Stressful Life Events and the Onset of Major Depression,” American Journal of Psychiatry 156 (1999): 837–41.

149 It you induce inflammatory reactions: C. L. Raison et al., “A Randomized Controlled Trial of the Tumor Necrosis Factor Antagonist Infliximab for Treatment-Resistant Depression: The Role of Baseline Inflammatory Biomarkers,” JAMA Psychiatry 70 (2013): 31–41; Neil A. Harrison et al., “Inflammation Causes Mood Changes Through Alterations in Subgenual Cingulate Activity and Mesolimbic Connectivity,” Biological Psychiatry 66, no. 5 (2009): 407–14; Naomi I. Eisenberger et al., “Inflammation-Induced Anhedonia: Endotoxin Reduces Ventral Striatum Responses to Reward,” Biological Psychiatry 68, no. 8 (2010): 748–54.

149 Chronically stress a laboratory animal: P. Willner, “Chronic Mild Stress (CMS) Revisited: Consistency and Behavioral-Neurobiological Concordance in the Effects of CMS,” Neuropsychobiology 52 (2005): 90–110.

149 anti-inflammatory agents: Michael Maes, “The Cytokine Hypothesis of Depression: Inflammation, Oxidative & Nitrosative Stress (IO&NS) and Leaky Gut as New Targets for Adjunctive Treatments in Depression,” Neuro Endocrinol Lett 29, no. 3 (2008a): 287–91.

149 Depressed people: Charles L. Raison et al., “Cytokines Sing the Blues: Inflammation and the Pathogenesis of Depression,” Trends in Immunology 27, no. 1 (2006): 24–31.

149 markers, called cytokines, are higher: Y. Dowlati et al., “A Meta-analysis of Cytokines in Major Depression,” Biological Psychiatry 67, no. 5 (2010): 446–57; Janice K. Kiecolt-Glaser et al., “Depressive Symptoms, Omega-6: Omega-3 Fatty Acids, and Inflammation in Older Adults,” Psychosomatic Medicine 69, no. 3 (2007): 217–24; A. H. Miller et al., “Inflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression,” Biological Psychiatry 65 (2009): 732–41.

149 lower in those who’ve been successfully treated: Miller, Inflammation and It’s Discontens; Beatriz M. Currier and Charles B. Nemeroff, “Inflammation and Mood Disorders: Proinflammatory Cytokines and the Pathogenesis of Depression,” Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry 9, no. 3 (2010): 212–20.

149 intense suicidal ideation: A. O’Donovan et al., “Suicidal Ideation Is Associated with Elevated Inflammation in Patients with Major Depressive Disorder,” Depress Anxiety 30 (2013): 307–14.

149 Stressed-out patients with anxiety: Michael Maes et al., “The Effects of Psychological Stress on Humans: Increased Production of Pro-Inflammatory Cytokines and Th1-Like Response in Stress-Induced Anxiety,” Cytokine 10, no. 4 (1998): 313–18.

149 hepatitis drug interferon: Hitoshi Miyaoka et al., “Depression from Interferon Therapy in Patients with Hepatitis C,” American Journal of Psychiatry 156, no. 7 (1999): 1120.

149 neural circuitry of depression: K. J. Ressler and H. S. Mayberg, “Targeting Abnormal Neural Circuits in Mood and Anxiety Disorders: From the Laboratory to the Clinic,” Nature Neuroscience 10 (2007): 1116–24.

149 Giving proinflammatory cytokines: Raison et al., “A Randomized Controlled Trial of the Tumor Necrosis Factor Antagonist Infliximab,” 31-41.

149 Stress causing inflammation: Dantzer et al., “From Inflammation to Sickness and Depression,” 46–56.

150 looking at sick people: Mark Schaller et al., “Mere Visual Perception of Other People’s Disease Symptoms Facilitates a More Aggressive Immune Response,” Psychological Science 21, no. 5 (2010): 649–52.

150 inflammation leads to greater amygdala response: Tristen K. Inagaki et al., “Inflammation Selectively Enhances Amygdala Activity to Socially Threatening Images,” Neuroimage 59, no. 4 (2012): 3222–26.

150 cytokines target and sabotage: C. B. Zhu et al., “Interleukin-1 Receptor Activation by Systemic Lipopolysaccharide Induces Behavioral Despair Linked to MAPK Regulation of CNS Serotonin Transporters,” Neuropsychopharmacology 35 (2010): 2510–20

150 Cytokines also break down tryptophan: A. J. Rush et al., “Acute and Longer-Term Outcomes in ­Depressed Outpatients Requiring One or Several Treatment Steps: A STAR*D Report,” American Journal of Psychiatry 163 (2006): 1905–17; J. Couzin-Frankel, “Inflammation Bares a Dark Side,” Science 330 (2010): 1621.

151 make matters worse: By disrupting dopamine levels.

151 cytokines diminish motivation: T. Kumal et al., “Effects of Interferon-Alpha on Tyrosine Hydroxylase and Catecholeamine Levels in the Brains of Rats,” Life Sciences 67 (2000): 663–69; H. Shuto et al., “Repeated Interferon-Alpha Administration Inhibits Dopaminergic Neural Activity in the Mouse Brain,” Brain Research 747 (1997): 348–51.

151 also antagonize glutamate: L. McNally et al., “Inflammation, Glutamate, and Glia in Depression: A Literature Review,” CNS Spectrums 13 (2008): 501–10.

151 Nearly a third of depressed people: Brian E. Leonard, “The Immune System, Depression and the Action of Antidepressants,” Progress in Neuro-Psychopharmacology and Biological Psychiatry 25, no. 4 (2001): 767–80.

151 higher levels of proinflammatory markers: S. Lanquillon et al., “Cytokine Production and Treatment Response in Major Depressive Disorder,” Neuropsychopharmacology 22 (2000): 370–79; T. Eller et al., “Pro-Inflammatory Cytokines and Treatment Response to Escitalopram in Major Depressive Disorder,” Prog Neuropsychopharmacol Biol Psychiatry 32 (2008): 445–50; Raison et al., “A Randomized Controlled Trial of the Tumor Necrosis Factor Antagonist Infliximab,” 31–41.

151 Some researchers have used anti-inflammatory medications: Miller et al., “Inflammation and Its Discontents,” 732–41; Raison et al., “A Randomized Controlled Trial of the Tumor Necrosis Factor Antagonist Infliximab,” 31–41; E. Haroon et al., “Psychoneuroimmunology Meets Neuropsychopharmacology: Translational Implications of the Impact of Inflammation on Behavior,” Neuropsychopharmacology 37 (2012): 137–62.

151 Leaky barriers play a role: M. Maes et al., “The Gut-Brain Barrier in Major Depression: Intestinal Mucosal Dysfunction with an Increased Translocation of LPS from Gram Negative Enterobacteria (Leaky Gut) Plays a Role in the Inflammatory Pathophysiology of Depression,” Neuro Endocrinology Letters 29 (2008): 117–24.

151 and anxiety: D. O’Malley et al., “Distinct Alterations in Colonic Morphology and Physiology in Two Rat Models of Enhanced Stress-Induced Anxiety and Depression-like Behavior,” Stress 13 (2010): 114–22.

151 Infections and autoimmune diseases make the blood-brain barrier leaky: Dantzer et al., “From Inflammation to Sickness and Depression,” 46–56.

152 Increased inflammatory reactivity: Christoph Laske, et al., “Autoantibody Reactivity in Serum of Patients with Major Depression, Schizophrenia and Healthy Controls,” Psychiatry Research 158, no. 1 (2008): 83–86; Betty Diamond et al., “Losing Your Nerves? Maybe It’s the Antibodies,” Nature Reviews Immunology 9, no. 6 (2009): 449–56.

152 Several autoimmune diseases: Michael E. Benros et al., “Autoimmune Diseases and Severe Infections as Risk Factors for Mood Disorders: A Nationwide Study,” JAMA Psychiatry (2013): 1–9.

152 if you have infections or autoimmune disorders: Ibid.

152 higher risk: In looking at the timing of medical illnesses and mood disorders, one study showed that a prior infection occurred before the mood disorder in 32 percent of patients. A prior autoimmune illness, though far less common in the general population, occurred in 5 percent. Any history of hospitalization for infection increased the risk of a subsequent mood ­disorder by 62 percent. If you’re unlucky enough to have been felled by both an infection and an autoimmune illness, especially within the past year, then the risk for depression quadruples.

152 Chronic stress increases the risk: Anette Pedersen et al., “Influence of Psychological Stress on Upper Respiratory Infection—A Meta-analysis of Prospective Studies,” Psychosomatic Medicine 72, no. 8 (2010): 823–32.

152 Natural killer cells: Michael Irwin et al., “Depression and Reduced Natural Killer Cytotoxicity: A Longitudinal Study of Depressed Patients and Control Subjects,” Psycholocal Medicine 22 (1992): 1045-1045; Steven J. Schleifer et al., “Depression and Immunity: Clinical Factors and Therapeutic Course,” Psychiatry Research 85, no. 1 (1999): 63–69.

152 antidepressants augment their invader-fighting abilities: Matthew Gerald Frank et al., ­“Antidepressants Augment Natural Killer Cell Activity: In Vivo and in Vitro,” Neuropsychobiology 39, no. 1 (1999): 18–24.

152 Stress creates inflammation: Hans Selye, The Stress of Life (New York: McGraw-Hill, 1956).

152 People under extreme stress: Gary M. Franklin et al., “Stress and Its Relationship to Acute Exacerbations in Multiple Sclerosis,” Neurorehabilitation and Neural Repair 2, no. 1 (1988): 7–11.

152 In asthmatic kids: Glenn Affleck et al., “Mood States Associated with Transitory Changes in Asthma Symptoms and Peak Expiratory Flow,” Psychosomatic Medicine 62, no. 1 (2000): 61–68.

152 In premenopausal women who have heart attacks: Viola Vaccarino et al., “Sex Differences in Mental Stress–Induced Myocardial Ischemia in Young Survivors of an Acute Myocardial Infarction,” Psychosomatic Medicine (2014): 45–53.

152 women have greater coronary artery reactivity: B. Ostadal and P. Ostadal, “Sex-Based Differences in Cardiac Ischaemic Injury and Protection: Therapeutic Implications,” British Journal of Pharmacology 171, no. 3 (2014): 541–54.

153 The main factors that can trigger: H. Ursin, E. Baade, and S. Levine, The Psychobiology of Stress: A Study of Coping Men (New York: Academic Press, 1978).

153 Inescapable shocks: Mark L. Laudenslager et al., “Coping and Immunosuppression: Inescapable but Not Escapable Shock Suppresses Lymphocyte Proliferation,” Science 221, no. 4610 (1983): 568–70.

153 If you block a rat’s ability: Ewa Chelmicka-Schorr and Barry G. Arnason, “Nervous System–Immune System Interactions and Their Role in Multiple Sclerosis,” Annals of Neurology 36, no. S1 (1994): S29–S32.

153 control over their health-care issues: Carsten Wrosch et al., “Health Stresses and Depressive Symptomatology in the Elderly: The Importance of Health Engagement Control Strategies,” Health Psychology 21, no. 4 (2002): 340.

153 Subordinate female monkeys: Carol A. Shively et al., “Behavior and Physiology of Social Stress and Depression in Female Cynomolgus Monkeys,” Biological Psychiatry 41, no. 8 (1997): 871–82.

153 The higher your social position: Michael Marmot and Eric Brunner, “Epidemiological Applications of Long-Term Stress in Daily Life,” Everyday Biological Stress Mechanisms 22 (2004): 80–90.

153 social networking like Facebook: Ethan Kross, et al., “Facebook Use Predicts Declines in Subjective Well-Being in Young Adults,” PloS One 8, no. 8 (2013): e69841.

153 Certain repressive behaviors in women: Maté, When the Body Says No.

153 “rationality and anti-emotionality”: Ronald Grossarth-Maticek et al., “Psychosocial Factors as Strong Predictors of Mortality from Cancer, Ischaemic Heart Disease and Stroke: The Yugoslav Prospective Study,” Journal of Psychosomatic Research 29, no. 2 (1985): 167–76.

153 emotional factors are potentially more important to survival: S. M. Levy and B. D. Wise, “Psychosocial Risk Factors in Cancer Prognosis,” Stress and Breast Cancer (Chichester, UK: John Wiley, 1988).

154 Let your true feelings show: Lissa Rankin, TED Talks, 2011, https://www.youtube.com/watch?v=7tu9nJmr4Xs.

154 Resilience is a key component: Daphne Simeon et al., “Factors Associated with Resilience in Healthy Adults,” Psychoneuroendocrinology 32, no. 8 (2007): 1149–52.

154 Exposure to mild or moderate stressors: D. M. Lyons and K. J. Parker, “Stress Inoculation-Induced Indications of Resilience in Monkeys,” Journal of Traumatic Stress 20 (2007): 423–33; Laura Anderko et al., “Peer Reviewed: Promoting Prevention Through the Affordable Care Act: Workplace Wellness,” Preventing Chronic Disease 9 (2012). E175–E190.

154 Students cocooned by protective helicopter parents: Holly Rogers, “Mindfulness Meditation for Increasing Resilience in College Students,” Psychiatric Annals 43, no. 12 (2013): 545–48.

154 Rat pups separated from their mothers: B. P. Rutten et al., “Resilience in Mental Health: Linking Psychological and Neurobiological Perspectives,” Acta Psychiatrica Scandinavica 128, no. 1 (2013): 3–20.

154 stressful event: Rats actually secrete corticosterone, their version of cortisol.

154 A secure early attachment: Simeon et al., “Factors Associated with Resilience in Healthy Adults,” 1149–52; Maté, When the Body Says No.

154 sustained activation of the panic/stress circuitry: Christine D. Heim et al., “The Link Between Childhood Trauma and Depression: Insights from HPA Axis Studies in Humans,” Psychoneuroendocrinology 33, no. 6 (2008): 693–710.

154 People who’ve been traumatized: Lisa M. Shin et al., “Amygdala, Medial Prefrontal Cortex, and Hippocampal Function in PTSD,” Annals of the New York Academy of Sciences 1071, no. 1 (2006): 67–79.

155 baseline inflammation: A. Danese et al., “Elevated Inflammation Levels in Depressed Adults with a History of Childhood Maltreatment,” Archives of General Psychiatry 65 (2008): 409–415

155 higher inflammatory responses: Ibid., 2008; Miller et al., “Inflammation and Its Discontents,” 732–41.

155 The quality of early parenting: Maté, When the Body Says No.

155 How a mother cares for her infant: Christian Caldji et al., “Variations in Maternal Care in Infancy Regulate the Development of Stress Reactivity,” Biological Psychiatry 48, no. 12 (2000): 1164–74.

155 Adult rats who had been licked: Christian Caldji et al., “Maternal Care During Infancy Regulates the Development of Neural Systems Mediating the Expression of Fearfulness in the Rat,” PNAS 95, no. 9 (1998): 5335–40.

155 A recent study showed definitively that children: Gregory E. Miller et al., “A Family-Oriented Psychosocial Intervention Reduces Inflammation in Low-SES African American Youth,” Proceedings of the National Academy of Sciences 111, no. 31 (2014): 11287–92.

155 early parenting environment can strongly influence: Dong Liu et al., “Maternal Care, Hippocampal Glucocorticoid Receptors, and Hypothalamic-Pituitary-Adrenal Responses to Stress,” Science 277, no. 5332 (1997): 1659–62; Michael J. Meaney, and Moshe Szyf, “Environmental Programming of Stress Responses Through DNA Methylation: Life at the Interface Between a Dynamic Environment and a Fixed Genome,” Dialogs in Clinical Neuroscience 7, no. 2 (2005): 103.

155 In studies of rhesus monkeys: Michael Marmot and Richard Wilkinson, eds., Social Determinants of Health (New York: Oxford University Press, 2005).

156 Anxious mothers are likely: Gabor Maté, In the Realm of Hungry Ghosts: Close Encounters with Addiction (New York: Random House, 2008).

156 Mothers with severe PTSD: Rachel Yehuda et al., “Cortisol Levels in Adult Offspring of Holocaust Survivors: Relation to PTSD Symptom Severity in the Parent and Child,” Psychoneuroendocrinology 27, no. 1 (2002): 171–80.

156 Children, and even grandchildren: Lea Baider et al., “Transmission of Response to Trauma? Second-Generation Holocaust Survivors’ Reaction to Cancer,” American Journal of Psychiatry 157, no. 6 (2000): 904–10; Rachel Yehuda, and Linda M. Bierer, “Transgenerational Transmission of Cortisol and PTSD Risk.” Progress in Brain Research 167 (2007): 121–35.

156 You see this in laboratory animals: Micah Leshem and Jay Schulkin, “Transgenerational Effects of Infantile Adversity and Enrichment in Male and Female Rats,” Developmental Psychobiology 54, no. 2 (2012): 169–86; Alice Shachar-Dadon et al., “Adversity Before Conception Will Affect Adult Progeny in Rats,” Developmental Psychology 45, no. 1 (2009): 9.

156 If you mate a stressed-out rat: Hiba Zaidan et al., “Prereproductive Stress to Female Rats Alters Corticotropin Releasing Factor Type 1 Expression in Ova and Behavior and Brain Cortico­tropin Releasing Factor Type 1 Expression in Offspring,” Biological Psychiatry 74, no. 9 (2013): 680–87.

156 serotonin production: The enzyme that makes serotonin, tryptophan dehydroxylase.

156 your risk for depression, suicidality, or aggression: David A. Nielsen et al., “Suicidality and 5-Hydroxyindoleacetic Acid Concentration Associated with a Tryptophan Hydroxylase Polymorphism,” Archives of General Psychiatry 51, no. 1 (1994): 34; Stephen B. Manuck et al., “Aggression and Anger-Related Traits Associated with a Polymorphism of the Tryptophan Hydroxylase Gene,” Biological Psychiatry 45, no. 5 (1999): 603–14.

156 after you’ve been stressed-out: Derick E. Vergne and Charles B. Nemeroff, “The Interaction of Serotonin Transporter Gene Polymorphisms and Early Adverse Life Events on Vulnerability for Major Depression,” Current Psychiatry Reports 8, no. 6 (2006): 452–57; Avshalom Caspi et al., “Influence of Life Stress on Depression: Moderation by a Polymorphism in the 5-HTT Gene,” Science Signaling 301, no. 5631 (2003): 386.

156 genes that control the SSRI docking space: Elaine Fox et al., “Looking on the Bright Side: Biased Attention and the Human Serotonin Transporter Gene,” Proceedings of the Royal Society B: Biological Sciences 276, no. 1663 (2009): 1747–51; Jan-Emmanuel De Neve, “Functional Polymorphism (5-HTTLPR) in the Serotonin Transporter Gene Is Associated with Subjective Well-Being: Evidence from a U.S. Nationally Representative Sample,” Journal of Human Genetics 56, no. 6 (2011): 456–59; Stefanie Wagner et al., “The 5-HTTLPR Polymorphism Modulates the Association of Serious Life Events (SLE) and Impulsivity in ­Patients with Borderline Personality Disorder,” Journal of Psychiatric Research 43, no. 13 (2009): 1067–72.

156 patients who are more vulnerable to depression: Carolyn A. Fredericks et al., “Healthy Young Women with Serotonin Transporter SS Polymorphism Show a Pro-inflammatory Bias Under Resting and Stress Conditions,” Brain, Behavior, and Immunity 24, no. 3 (2010): 350–57.

156 getting depressed when they’re medically: K. Karg et al., “The Serotonin Transporter Promoter Variant (5-HTTLPR), Stress, and Depression Meta-analysis Revisited: Evidence of Genetic Moderation,” Archives of General Psychiatry 68 (2011): 444–54.

157 Change your mind about stress: Jeremy P. Jamieson et al., “Mind Over Matter: Reappraising Arousal Improves Cardiovascular and Cognitive Responses to Stress,” Journal of Experimental Psychology: General 141, no. 3 (2012): 417.

157 One study showed a whopping 43 percent risk: Abiola Keller et al., “Does the Perception That Stress Affects Health Matter? The Association with Health and Mortality,” Health Psychology 31, no. 5 (2012): 677.

157 Positive emotions prevent or undo: Barbara L. Fredrickson et al., “The Undoing Effect of Positive Emotions,” Motivation and Emotion 24, no. 4 (2000): 237–58; Barbara L. Fredrickson, “The Role of Positive Emotions in Positive Psychology: The Broaden-and-Build Theory of Positive Emotions,” American Psychologist 56, no. 3 (2001): 218.

157 Develop your ability to experience positive emotions: Inez Myin-Germeys et al., “Evidence That Moment-to-Moment Variation in Positive Emotions Buffer Genetic Risk for Depression: A Momentary Assessment Twin Study,” Acta Psychiatrica Scandinavica 115, no. 6 (2007): 451–57; Nicole Geschwind et al., “Meeting Risk with Resilience: High Daily Life Reward Experience Preserves Mental Health,” Acta Psychiatrica Scandinavica 122, no. 2 (2010): 129–38.

157 Women with more day-to-day positive emotions: Anthony D. Ong et al., “Psychological Resilience, Positive Emotions, and Successful Adaptation to Stress in Later Life,” Journal of Personality and Social Psychology 91, no. 4 (2006): 730.

157 More resilient folks are more likely: Michele M. Tugade and Barbara L. Fredrickson, “Resilient Individuals Use Positive Emotions to Bounce Back from Negative Emotional Experiences,” Journal of Personality and Social Psychology 86, no. 2 (2004): 320.

157 For patients with depression: Suzanne Meeks et al., “The Pleasant Events Schedule–Nursing Home Version: A Useful Tool for Behavioral Interventions in Long-Term Care,” Aging and Mental Health 13, no. 3 (2009): 445–55.

158 Chronic stress chips away: Rita B. Effros, “Telomere/telomerase Dynamics Within the Human Immune System: Effect of Chronic Infection and Stress,” Experimental Gerontology 46, no. 2 (2011): 135–40.

158 In a study of women taking care: Elissa S. Epel et al., “Accelerated Telomere Shortening in Response to Life Stress,” PNAS 101, no. 49 (2004): 17312–15.

158 telomere length: Also the lower her level of the enzyme telomerase, which is responsible for adding length to the telomere.

158 Chronic inflammation can shorten: Elissa Epel, personal communication via telephone, March 25, 2014.

158 As immune cells age: R. B. Effros et al., “The Role Of CD8 T Cell Replicative Senescence in Human Aging,” Immunological Reviews 205 (2005): 147–57.

158 predict the onset of diseases such as cancer: P. Willeit et al., “Fifteen-Year Follow-up of Association Between Telomere Length and Incident Cancer and Cancer Mortality,” JAMA 306 (2011): 42–44.

158 dementia: L. S. Honig et al., “Association of Shorter Leukocyte Telomere Repeat Length with Dementia and Mortality,” Archives of Neurology (2012): 1–8.

158 Abdominal obesity shortens: R. Farzaneh-Far et al., “Association of Marine Omega-3 Fatty Acid Levels with Telomeric Aging in Patients with Coronary Heart Disease,” JAMA 303 (2010): 250–57.

158 exercise will help to keep them long: C. Werner et al., “Physical Exercise Prevents Cellular Senescence in Circulating Leukocytes and in the Vessel Wall,” Circulation 120 (2009): 2438–47; Eli Puterman and Elissa Epel, “An Intricate Dance: Life Experience, Multisystem Resiliency, and Rate of Telomere Decline Throughout the Lifespan,” Social and Personality Psychology Compass 6, no. 11 (2012): 807–25.

158 Less stress and better sleep: J. Lin et al., “Telomeres and Lifestyle Factors: Roles in Cellular Aging,” ­Mutation Research 730 (2012): 85–89; Puterman and Epel, “An Intricate Dance.”

159 mindfulness-based practices: Tonya L. Jacobs et al., “Intensive Meditation Training, Immune Cell Telomerase Activity, and Psychological Mediators,” Psychoneuroendocrinology 36, no. 5 (2011): 664–81; J. Daubenmier et al., “Changes in Stress, Eating, and Metabolic Factors Are Related to Changes in Telomerase Activity in a Randomized Mindfulness Intervention Pilot Study,” Psychoneuroendocrinology 37 (2012): 917–28; H. Lavretsky et al., “A Pilot Study of Yogic Meditation for Family Dementia Caregivers with Depressive Symptoms: Effects on Mental Health, Cognition, and Telomerase Activity,” International Journal of Geriatric Psychiatry 28, no. 1 (2013): 57–65.

159 Expert meditators: Perla Kaliman et al., “Rapid Changes in Histone Deacetylases and Inflammatory Gene Expression in Expert Meditators,” Psychoneuroendocrinology 40 (2014): 96–107.

159 Social connectedness improves resilience: M. DeRosier et al., “The Potential Role of Resilience Education for Preventing Mental Health Problems for College Students,” Psychiatric Annals 43, no. 12 (2013): 538–44.

159 Positive social interactions: Markus Heinrichs et al., “Social Support and Oxytocin Interact to Suppress Cortisol and Subjective Responses to Psychosocial Stress,” Biological Psychiatry 54, no. 12 (2003): 1389–98.

160 Social support can lower cortisol levels: C. Kirschbaum et al., “The ‘Trier Social Stress Test’—A Tool for Investigating Psychobiological Stress Responses in a Laboratory Setting,” Neuropsycho­biology 28 (1993): 76 –81; K. Sayal et al., “Effects of Social Support During Weekend Leave on Cortisol and Depression Ratings: A Pilot Study,” Journal of Affective Disorders 71(2002): 153–57.

160 lower cardiovascular reactivity: S. J. Lepore et al., “Social Support Lowers Cardiovascular Reactivity to an Acute Stressor,” Psychosomatic Medicine 55 (1993): 518–24.

160 ameliorate symptoms of depression: J. C. Hays et al., “Does Social Support Buffer Functional Decline in Elderly Patients with Unipolar Depression? American Journal of Psychiatry 158 (2001): 1850–55; Sayal et al., “Effects of Social Support During Weekend Leave,” 153–57.

160 Oxytocin has anti-inflammatory: Martin Clodi et al., “Oxytocin Alleviates the Neuroendocrine and Cytokine Response to Bacterial Endotoxin in Healthy Men,” American Journal of Physiology-Endocrinology and Metabolism 295, no. 3 (2008): E686–E691.

160 relaxes blood vessels: Sybil Lloyd and Mary Pickford, “The Effect of Oestrogens and Sympathetic Denervation on the Response to Oxytocin of the Blood Vessels in the Hind Limb of the Dog” Journal of Physiology 163, no. 2 (1962): 362–71.

160 Frequent hugs: Kathleen C. Light et al., “More Frequent Partner Hugs and Higher Oxytocin Levels Are Linked to Lower Blood Pressure and Heart Rate in Premenopausal Women,” Biological Psychology 69, no. 1 (2005): 5–21.

160 oxytocin receptors on the heart: Marek Jankowski et al., “Anti-inflammatory Effect of Oxytocin in Rat Myocardial Infarction,” Basic Research in Cardiology 105, no. 2 (2010): 205–18.

160 Socially isolated adults: Lisa F. Berkman and S. Leonard Syme, “Social Networks, Host Resistance, and Mortality: A Nine-Year Follow-up Study of Alameda County Residents,” American Journal of Epidemiology 109, no. 2 (1979): 186–204; James S. House et al., “Social Relationships and Health,” Science 241, no. 4865 (1988): 540–45.

160 Lonely people have worse sleep: John T. Cacioppo et al., “Loneliness and Health: Potential Mechanisms,” Psychosomatic Medicine 64, no. 3 (2002): 407–17.

160 more depressive symptoms: John T. Cacioppo and William Patrick, Loneliness: Human Nature and the Need For Social Connection (New York: WW Norton & Company, 2008).

160 Isolation also impairs immune functioning: George M. Slavich et al., “Neural Sensitivity to Social Rejection Is Associated with Inflammatory Responses to Social Stress,” PNAS 107, no. 33 (2010): 14817–22; W. B. Malarkey et al., “Behavior: The Endocrine-Immune Interface and Health Outcomes,” Advances in Psychosomatic Medicine 22 (2001): 104–15; M. Irwin et al., “Neuropeptide Y and Natural Killer Cell Activity: Findings in Depression and Alzheimer Caregiver Stress,” The FASEB Journal 5, no. 15 (1991): 3100–3107.

160 Studies of stress, isolation, and neuroplasticity: C. Pugh et al., “Role of Interleukin-1 Beta in Impairment of Contextual Fear Conditioning Caused by Social Isolation,” Behavioral Brain Research 106, no. 1 (1999): 109–18; R. M. Barrientos et al., “Brain-Derived Neurotrophic Factor Mrna Downregulation Produced by Social Isolation Is Blocked by Intrahippocampal Interleukin-1 Receptor Antagonist,” Neuroscience 121, no. 4 (2003): 847–53.

160 memory formation: If you stress lab rats, they release a proinflammatory cytokine called IL1-beta. If you take them away from their group housing, shock them in a separate space, and return them to their group, they’re understandably stressed when you take them back to the shocking room; they remember where they got the pain. But if you take them away from their pals, shock them, but then put them in solitary confinement, they don’t remember the shocking place. Being alone not only activates IL1-beta but also tanks the BDNF necessary to grow neuronal connections and learn something. Stress activates inflammation, which turns off the neurotrophic signals. If you block the IL1-beta, you block those changes, and you don’t see the hippocampal shrinkage and stupidity.

160 Isolation also leads to impaired top-down: A. B. Silva-Gómez et al., “Decreased Dendritic Spine Density on Prefrontal Cortical and Hippocampal Pyramidal Neurons in Post-weaning Social Isolation Rats,” Brain Reearch 983 (2003): 128–36 (2003).

161 Not only are cannabinoids anti-inflammatory: John M. McPartland and Ethan B. Russo, “Cannabis and Cannabis Extracts: Greater Than the Sum of Their Parts?” Journal of Cannabis Therapeutics 1, no. 3–4 (2001): 103–32; S. H. Burstein and R. B. Zurier, “Cannabinoids, Endo­cannabinoids, and Related Analogs in Inflammation,” AAPS Journal 11 (2009): 109–19; Julie Holland, ed., The Pot Book: A Complete Guide to Cannabis (Rochester, VT: Inner Traditions/Bear & Co, 2010).

161 Cannabinoids alter immune reactions: Radu Tanasescu and Cris S. Constantinescu, “Cannabinoids and the Immune System: An Overview,” Immunobiology 215, no. 8 (2010): 588–97.

161 Anandamide, our main internal cannabis molecule: M. N. Hill and J. G. Tasker, “Endocannabinoid Signaling, Glucocorticoid-Mediated Negative Feedback, and Regulation of the Hypothalamic-Pituitary-­Adrenal Axis,” Neuroscience 204 (2012): 5–16.

161 Higher anandamide levels: R. J. Bluett et al., “Central Anandamide Deficiency Predicts Stress-Induced Anxiety: Behavioral Reversal Through Endocannabinoid Augmentation,” Translational Psychiatry 4, no. 7 (2014): e408.

161 anandamide levels rise: Matthew N. Hill et al., “Rapid Elevations in Limbic Endocannabinoid Content by Glucocorticoid Hormones in Vivo,” Psychoneuroendocrinology 35, no. 9 (2010): 1333–38.

161 pot affects memory: Nadia Solowij and Robert Battisti, “The Chronic Effects of Cannabis on Memory in Humans: A Review,” Current Drug Abuse Reviews 1, no. 1 (2008): 81–98.

161 Boosting anandamide can promote this forgetting: Ozge Gunduz-Cinar et al., “Amygdala FAAH and Anandamide: Mediating Protection and Recovery from Stress,” Trends in Pharmacological Sciences 34, no. 11 (2013): 637–44.

161 Veterans with PTSD may smoke cannabis: Murdoch Leeies et al., “The Use of Alcohol and Drugs to Self-Medicate Symptoms of Posttraumatic Stress Disorder,” Depression and Anxiety 27, no. 8 (2010): 731–36; George R. Greer et al., “PTSD Symptom Reports of Patients Evaluated for the New Mexico Medical Cannabis Program,” Journal of Psychoactive Drugs 46, no. 1 (2014): 73–77.

161 attempting to rebalance: Matthew N. Hill et al., “Reductions in Circulating Endocannabinoid Levels in Individuals with Post-traumatic Stress Disorder Following Exposure to the World Trade Center Attacks,” Psychoneuroendocrinology 38, no. 12 (2013): 2952–61.

161 Many psychiatric disorders: Ethan B. Russo, “Clinical Endocannabinoid Deficiency (Cecd): Can This Concept Explain Therapeutic Benefits of Cannabis In Migraine, Fibromyalgia, Irritable Bowel Syndrome and Other Treatment-Resistant Conditions?” Neuroendocrinology Letters 25, no. 1–2 (2003): 31–39.

161–162 Endocannabinoid levels: Matthew N. Hill et al., “Circulating Endocannabinoids and N-Acyl Ethanolamines Are Differentially Regulated in Major Depression and Following Exposure to ­Social Stress,” Psychoneuroendocrinology 34, no. 8 (2009): 1257–62.

162 Mice raised to have no cannabis receptors: Matthew N. Hill et al., “Alterations in Corticolimbic Dendritic Morphology and Emotional Behavior in Cannabinoid CB1 Receptor–Deficient Mice Parallel the Effects of Chronic Stress,” Cerebral Cortex 21, no. 9 (2011): 2056–64.

162 may represent a good animal model: O. Valverde and M. Torrens, “CB1 Receptor–Deficient Mice as a Model for Depression,” Neuroscience 204 (2012): 193–206.

162 Animal studies show that enhancing endocannabinoid: Matthew N. Hill and Boris B. Gorzalka, “Pharmacological Enhancement of Cannabinoid CB1 Receptor Activity Elicits an Antidepressant-like Response in the Rat Forced Swim Test,” European Neuropsychopharmacology 15, no. 6 (2005): 593–99.

162 One potential site of action: Jasmeer P. Chhatwal et al., “Enhancing Cannabinoid Neurotransmission Augments the Extinction of Conditioned Fear,” Neuropsychopharmacology 30, no. 3 (2005): 516–24. O. Gunduz-Cinar et al., “Convergent Translational Evidence of a Role for Anandamide in Amygdala-­Mediated Fear Extinction, Threat Processing and Stress-Reactivity,” Molecular Psychiatry 18, no. 7 (2013a): 813–23.

162 Inhibiting FAAH, which raises anandamide levels: Gunduz-Cinar et al., “Amygdala FAAH and Anandamide,” 637–44.

162 Variations in the human FAAH gene: Gunduz-Cinar et al., “Convergent Translational Evidence of a Role for Anandamide,” 813–23.

162 Women and cannabis: Michelle Sexton, “The Female: Cannabis Relationship,” Ladybud.com, February 25, 2014.

162 Anandamide levels fluctuate: N. H. Lazzarin et al., “Fluctuations of Fatty Acid Amide Hydrolase and Anandamide Levels During the Human Ovulatory Cycle,” Gynecological Endocrinology 18, no. 4 (2004): 212–18.

162 Estrogen inhibits FAAH activity: Matthew N. Hill et al., “Estrogen Recruits the Endocannabinoid System to Modulate Emotionality,” Psychoneuroendocrinology 32, no. 4 (2007): 350–57.

162–163 This same estrogen-FAAH interaction: Mauro Maccarrone et al., “Progesterone Up-Regulates Anandamide Hydrolase in Human Lymphocytes: Role of Cytokines and Implications for Fertility,” The Journal of Immunology 166, no. 12 (2001): 7183–89.

163 full of cannabinoid receptors: Michael C. Dennedy et al., “Cannabinoids and the Human Uterus During Pregnancy,” American Journal of Obstetrics and Gynecology 190, no. 1 (2004): 2–9.

163 oldest known recommended use for cannabis: Paul Ghalioungui, The Ebers Papyrus: A New English Translation, Commentaries and Glossaries (Cairo: Academy of Scientific Research and Technology, 1987).

163 Queen Victoria was prescribed cannabis: British Medical Association, Therapeutic Uses of Cannabis (UK: CRC Press, 1997).

163 long-standing use of cannabinoids: Wei-Ni Lin Curry, “Hyperemesis Gravidarum and Clinical Cannabis: To Eat or Not to Eat?” Journal of Cannabis Therapeutics 2, no. 3–4 (2002): 63–83; Rachel E. Westfall et al., “Survey of Medicinal Cannabis Use Among Childbearing Women: Patterns of Its Use in Pregnancy and Retroactive Self-Assessment of Its Efficacy Against ‘Morning Sickness.’    ” Complementary Therapies in Clinical Practice 12, no. 1 (2006): 27–33.

Chapter Eight: Food: A Drug We Can’t Resist

165 Being loved, cared for, and fed: Doidge, The Brain That Changes Itself.

166 food issues: When obese women are shown pictures of high-calorie foods, their brains show greater activity in regions associated with anticipating reward than do the brains of women with more normal weight.

166–167 in a study pitting Oreos against cocaine: Joseph Schroeder, “Oreos Trigger More Robust Dopamine Response and Place-Preference Than Cocaine in Rats,” presented at Society for Neuroscience conference in San Diego, California, 2013.

167 junk foods: Rats fed junk-food diets need increasing amounts to trigger the release of dopamine and get the same brain boost. They become obese and lose control of their ability to stop eating, much like alcoholics who can’t stop at one drink. Even when electric shocks are applied to their feet, which would stop control groups from eating rat chow, if the food is cheesecake, frosting, or bacon, the rats keep on eating. When the junk food is removed and replaced with healthy food, the rats stage a hunger strike, basically starving themselves for two weeks because they’re so upset.

167 Sugar creates a “bliss point”: Moss, Salt, Sugar, Fat.

167 Fat content is difficult to discern: Mirre Viskaal-van Dongen et al., “Hidden Fat Facilitates Passive Overconsumption,” Journal of Nutrition 139, no. 2 (2009): 394–99; Drewnowski and Schwartz, “Invisible Fats,” 203–17.

167 Even artificial sweeteners can get us hooked: M. D. Puhl et al., “Environmental Enrichment Protects Against the Acquisition of Cocaine Self-Administration in Adult Male Rats, But Does Not Eliminate Avoidance of a Drug-Associated Saccharin Cue,” Behavioural Pharmacology 23 (2012): 43–53; D. J. Stairs, et al., “Effects of Environmental Enrichment on Extinction and Reinstatement of Amphetamine Self-­Administration and Sucrose-Maintained Responding,” Behavioural Pharmacology 17 (2006): 597–604.

167 interfere with self-admistration: Rats show they prefer saccharine-sweetened water over cocaine.

167 Rats fed a high-sugar diet: Carlo Colantuoni et al., “Evidence That Intermittent, Excessive Sugar Intake Causes Endogenous Opioid Dependence,” Obesity Research 10, no. 6 (2002): 478–88.

167 Giving women who are binge eaters: A. Drewnowski and M. Schwartz, “Invisible Fats: Sensory Assessment of Sugar/Fat Mixtures,” Appetite 14, no. 3 (1990): 203–17.

167 the endorphin system: Walter Kaye, “Neurobiology of Anorexia and Bulimia Nervosa,” Physiology & Behavior 94, no. 1 (2008): 121–35.

167 Stress and emotions affect your gastrointestinal system: Maté, When the Body Says No.

168 having a gut feeling: Emeran A. Mayer, “Gut Feelings: The Emerging Biology of Gut–Brain Communication,” Nature Reviews Neuroscience 12, no. 8 (2011): 453–66.

168 less inhibitory control in response to these reward cues: Ashley Gearhardt and Kelly D. Brownell, “Neural Correlates of Food Addiction,” Archives of Geneneral Psychiatry 68, no. 8 (2011): 808–16.

168 The brain’s ability to register dopamine surges: Gene-Jack Wang et al, “Brain Dopamine and Obesity,” The Lancet 357, no. 9253 (February 3, 2001): 354–57.

168 Drugs and food compete in the brain: Doug Brunk, “Neural Correlates of Addictive-Like Eating Behavior Studied,” Clinical Psychiatry News, April 4, 2011.

169 solid evidence that twelve-step programs: Diane H. Wasson and Mary Jackson, “An Analysis of the Role of Overeaters Anonymous in Women’s Recovery from Bulimia Nervosa,” Eating Disorders 12, no. 4 (2004): 337–56; Nattie Ronel, Natti and Galit Libman, “Eating Disorders and Recovery: Lessons from Overeaters Anonymous,” Clinical Social Work Journal 31, no. 2 (2003): 155–71.

169 the dopamine reward pathway: Brian Knutson et al., “Dissociation of Reward Anticipation and Outcome with Event-Related fMRI,” Neuroreport 12, no. 17 (2001): 3683–87; John P. O’Doherty et al., “Neural Responses During Anticipation of a Primary Taste Reward,” Neuron 33, no. 5 (2002): 815–26.

169 don’t stop eating: The way to prevent the munchies is to simply keep food out of your mouth. The endocannabinoid system is designed to make you keep eating, so just don’t start.

170 The hormone leptin: Ioannis Kyrou et al., “Stress, Visceral Obesity, and Metabolic Complications,” Annals of the New York Academy of Sciences 1083, no. 1 (2006): 77–110.

170 how fat you really are: Leptin also lets your reproductive system know whether “all systems are go” and you have enough energy reserves to conceive.

170 appetite suppressant: In animals it was found to reduce all food intake, in particular “palatable” food intake, and obesity.

171 Or drink them: Michael G. Tordoff and Annette M. Alleva, “Effect of Drinking Soda Sweetened with Aspartame or High-Fructose Corn Syrup on Food Intake and Body Weight,” The American Journal of Clinical Nutrition 51, no. 6 (1990): 963–69; Michael G. Tordoff and Annette M. Alleva, “Oral Stimulation with Aspartame Increases Hunger,” Physiology & Behavior 47, no. 3 (1990): 555–59; J. H. Lavin et al., “The Effect of Sucrose- and Aspartame-Sweetened Drinks on Energy Intake, Hunger and Food Choice of Female, Moderately Restrained Eaters,” Int J Obes Relat Metab Disord 21, no. 1 (1997): 37–42.

171 Artificial sweeteners do not satiate: Peter J. Rogers and John E. Blundell, “Separating the Actions of Sweetness and Calories: Effects of Saccharin and Carbohydrates on Hunger and Food Intake in Human Subjects,” Physiology & Behavior 45, no. 6 (1989): 1093–99; Qing Yang, “Gain Weight by ‘Going Diet?’ Artificial Sweeteners and the Neurobiology of Sugar Cravings: Neuroscience 2010,” The Yale Journal of Biology and Medicine 83, no. 2 (2010): 101.

171 can make you fat: G. A. Colditz et al., “Patterns of Weight Change and Their Relation to Diet in a Cohort of Healthy Women,” American Journal of Clinical Nutrition 51, no. 6 (1990): 1100–1105; S. P. Fowler et al., “Fueling the Obesity Epidemic? Artificially Sweetened Beverage Use and Long-Term Weight Gain,” Obesity 16, no. 8 (2008): 1894-1900.

172 A high-protein, low-carb diet: M. Hession et al., “Systematic Review of Randomized Controlled Trials of Low-Carbohydrate Vs. Low-Fat/Low- Calorie Diets in the Management of Obesity and Its Comorbiditie, “Obesity Reviews 10, no. 1 (2009): 36–50.

172 lower your risk for heart disease: L. A. Bazzano et al., “Effects of Low-Carbohydrate and Low-Fat Diets: A Randomized Trial,” Annals of Internal Medicine 161 (2014): 309–18; T. Hu and L. A. Bazzano, “The Low-Carbohydrate Diet and Cardiovascular Risk Factors: Evidence from Epidemiologic Studies,” Nutrition, Metabolism and Cardiovascular Diseases 24, no. 4 (2014): 337–43.

172 Numerous studies suggest that the omega-3: Da Young Oh et al., “GPR120 Is an Omega-3 Fatty Acid Receptor Mediating Potent Anti-inflammatory and Insulin-Sensitizing Effects,” Cell 142, no. 5 (2010): 687–98.

172–173 What else reverses insulin resistance? Cannabis: T. C. Kirkham, “Endocannabinoids in the Regulation of Appetite and Body Weight,” Behavioral Pharmacology 16, no. 5–6 (2005):

297–313.

173 Chronic pot smokers: Yann Le Strat and Bernard Le Foll, “Obesity and Cannabis Use: Results from 2 Representative National Surveys,” American Journal of Epidemiology 174, no. 8 (2011): 929.

173 better cholesterol and fatty acid levels: Elizabeth A. Penner et al., “The Impact of Marijuana Use on Glucose, Insulin, and Insulin Resistance Among U.S. Adults,” American Journal of Medicine 126, no. 7 (2013): 583–89.

173 The third hormone, ghrelin: S. Taheri et al., “Short Sleep Duration Is Associated with Reduced Leptin, Elevated Ghrelin, and Increased Body Mass Index,” PLoS Medicine 1, no. 3 (2004): e62.

173 In obese people: P. J. English et al., “Food Fails to Suppress Ghrelin Levels in Obese Humans,” Journal of Clinical Endocrinology and Metabolism 87, no. 6 (2002): 2984.

173 Twins, whether they grow up together: Albert J. Stunkard et al., “A Twin Study of Human Obesity,” JAMA 256, no. 1 (1986): 51–54.

173 or are separated at birth: Albert J. Stunkard et al., “The Body-Mass Index of Twins Who Have Been Reared Apart,” New England Journal of Medicine 322, no. 21 (1990): 1483–87.

173 children adopted out have the BMIs: Albert J. Stunkard et al., “An Adoption Study of Human Obesity,” New England Journal of Medicine 314, no. 4 (1986a): 193–98.

173 Australian researchers: P. Sumithran et al., “Long-Term Persistence of Hormonal Adaptations to Weight Loss,” New England Journal of Medicine 365, no. 17 (2011):1597–1604.

174 whipped cream: On the other hand, you don’t want to make yourself crazy trying to eat local, pesticide free, organic, vegan, etc. There’s a new eating disorder called orthorexia for people who are getting way too obsessive about what they eat.

174 American-born children don’t live as long: Gopal K. Singh and Barry A. Miller, “Health, Life Expectancy, and Mortality Patterns Among Immigrant Populations in the United States,” Canadian Journal of Public Health 95, no. 3 (2003): 114–21.

174 One study that divided people into two diets: Tasnime N. Akbaraly et al., “Dietary Pattern and Depressive Symptoms in Middle Age,” British Journal of Psychiatry 195, no. 5 (2009): 408–13.

175 diets high in fats and low in carbs: Westman et al,. “Low-Carbohydrate Nutrition and Metabolism,” 276–84; F. L. Santos et al., “Systematic Review and Meta-analysis of Clinical Trials of the Effects of Low Carbohydrate Diets on Cardiovascular Risk Factors,” Obesity Reviews 13, no. 11 (2012): 1048–66.

175 in particular belly fat loss: Ronald M. Krauss et al., “Separate Effects of Reduced Carbohydrate Intake and Weight Loss on Atherogenic Dyslipidemia,” American Journal of Clinical Nutrition 83, no. 5 (2006): 1025–31.

175 lower blood sugar and insulin levels: Westman et al., “Low-Carbohydrate Nutrition and Metabolism,” 276–84; Hession et al., “Systematic Review of Randomized Controlled Trials,” 36–50.

175 Saturated fat and cholesterol don’t increase: Patty W. Siri-Tarino et al., “Meta-analysis of Prospective Cohort Studies Evaluating the Association of Saturated Fat with Cardiovascular Disease,” American Journal of Clinical Nutrition 91, no. 3 (2010): 535–46.

175 The countries eating the most saturated fat: Robert Hoenselaar, “Saturated Fat and Cardiovascular Disease: The Discrepancy Between the Scientific Literature and Dietary Advice,” Nutrition 28, no. 2 (2012): 118–23.

175 Low-carb diets: Bonnie J. Brehm et al., “A Randomized Trial Comparing a Very Low Carbohydrate Diet and a Calorie-Restricted Low Fat Diet on Body Weight and Cardiovascular Risk Factors in Healthy Women,” Journal of Clinical Endocrinology & Metabolism 88, no. 4 (2003): 1617–23.

175 cholestrol numbers: High-density lipoprotein (HDL) is the “good” type of cholesterol. The low-density lipoproteins (LDL) have the reputation of being the “bad” cholesterol, but it’s not that simple. There are smaller, dense LDLs that are bad for you, and larger, fluffy ones that are good for you, just like my mother’s matzo balls. There is an unholy trinity, called pattern B, where you see dense LDLs, low levels of desirable HDLS, and high triglycerides, a setup for narrowing the arteries with plaques, causing heart attacks or strokes. The bad matzo balls—the dense LDLs—are linked to inflammation and many medical illnesses but are not even produced by eating fat. They’re produced by excess sugars and carbs. That is a big shift from the old thinking on diet and cholesterol levels.

175 okay again: They increase LDLs, but the good, fluffy kind, and they also increase beneficial HDLs.

175 Trans fats are still bad: Esther Lopez-Garcia et al., “Consumption of Trans Fatty Acids Is Related to Plasma Biomarkers of Inflammation and Endothelial Dysfunction,” Journal of Nutrition 135, no. 3 (2005): 562–66; Rajiv Chowdhur et al., “Association of Dietary, Circulating, and Supplement Fatty Acids with Coronary Risk: A Systematic Review and Meta-analysis,” Annals of Internal Medicine 160, no. 6 (2014): 398–406.

175 Monounsaturated fats, found in nuts: Penny M. Kris-Etherton et al., “Nuts and Their Bioactive Constituents: Effects on Serum Lipids and Other Factors That Affect Disease Risk,” American Journal of Clinical Nutrition 70, no. 3 (1999): 504s–511s.

176 Now, it turns out: Unique to coconut oil are its antiviral and antifungal properties. Around half the fat of coconut oil is lauric acid, a fatty acid rarely found in nature, though it is in human breast milk. Infants convert it to monolaurin, which kills some bacteria, giardia, measles, the flu, herpes, and HIV. Coconut oil is also great for your hair, cuticles, and dry skin. It can even clean your teeth. It is also a good lubricant for sex.

176 coconut oil is the hot new thing: Trent Gordon, Coconut Oil—The Numerous Advantages: Hygiene, Diet and Weight Loss (Newark, Del.: Speedy Publishing LLC, 2013).

176 a way to add a bit of sweetener: Monica L. Assunção et al., “Effects of Dietary Coconut Oil on the Biochemical and Anthropometric Profiles of Women Presenting Abdominal Obesity,” Lipids 44, no. 7 (2009): 593–601.

176 Raw vegetables are important: Oyinlola Oyebode et al., “Fruit and Vegetable Consumption and All-Cause, Cancer and CVD Mortality: Analysis of Health Survey for England Data,” Journal of Epidemiology and Community Health (2014): jech-2013.

176 alkanize your body: Animal products, grains, and processed foods can be acidic, while most vegetables, beans, and seeds are alkaline. Deep breathing, drinking spring water, and moderate exercise are also ways to alkalinize.

176 maintaining bone health: Tim Arnett, “Regulation of Bone Cell Function by Acid-Base Balance,” Proceedings of the Nutrition Society 62, no. 2 (2003): 511–20.

176 lowering your risk for obesity: Mark Hyman, “Systems Biology, Toxins, Obesity, and Functional Medicine,” Altern Ther Health Med 13, no. 2 (2007): S134–S139.

176 diabetes, and heart disease: R. Jaffe, “The Alkaline Way in Digestive Health,” in Bioactive Food as Dietary Interventions for Liver and Gastrointestinal Disease: Bioactive Foods in Chronic Disease States (London: Academic Press, 2012): 1–21.

176 strong evidence that ACV lowers insulin: Y. Ostman et al., “Vinegar Supplementation Lowers Glucose and Insulin Responses and Increases Satiety After a Bread Meal in Healthy Subjects,” European Journal of Clinical Nutrition 59 (2005): 983–88.

176 keep diabetes in check: Carol S. Johnston et al., “Preliminary Evidence That Regular Vinegar Ingestion Favorably Influences Hemoglobin A1c Values in Individuals with Type 2 Diabetes Mellitus,” Diabetes Research and Clinical Practice 84, no. 2 (2009): e15–e17.

176 drive weight loss: Tomoo Kondo et al., “Acetic Acid Upregulates the Expression of Genes for Fatty Acid Oxidation Enzymes in Liver to Suppress Body Fat Accumulation,” Journal of Agricultural and Food Chemistry 57, no. 13 (2009): 5982–86.

176 improve cholesterol levels: Nilgun H. Budak et al., “Effects of Apple Cider Vinegars Produced with Different Techniques on Blood Lipids in High-Cholesterol-Fed Rats,” Journal of Agricultural and Food Chemistry 59, no. 12 (2011): 6638–44.

176 reduce inflammation: Christine M. Ross and John J. Poluhowich, “The Effect of Apple Cider Vinegar on Adjuvant Arthritic Rats,” Nutrition Research 4, no. 4 (1984): 737–41.

176 acetic acid in vinegar inhibits the digestion of starches: Johnston et al., “Preliminary Evidence That Regular Vinegar Ingestion Favorably Influences Hemoglobin,” e15–e17.

176 won’t be so bloated: Apple cider vinegar is made from the alcohol obtained by the fermentation of apples by yeast and bacteria. If you can get raw ACV, it’s even better, because pasteurization will   kill off some of the good stuff, like enzymes. A tablespoon of ACV diluted in plenty of water before a meal is a common recommendation for people trying to lose weight. Dilution is crucial, because all vinegar is caustic to tooth enamel and stomach lining if not ­watered down.

177 uses only the sugar glucose: O. E. Owen et al., “Brain Metabolism During Fasting,” Journal of Clinical Investigation 46, no. 10 (1967): 1589; A. Rao et al., “A Randomized, Double-Blind, Placebo-Controlled Pilot Study of a Probiotic in Emotional Symptoms of Chronic Fatigue Syndrome,” Gut Pathogens 1, no. 1 (2009): 1–6.

177 Chronic consumption of fructose: Karen L. Teff et al., “Dietary Fructose Reduces Circulating Insulin and Leptin, Attenuates Postprandial Suppression of Ghrelin, and Increases Triglycerides in Women,” Journal of Clinical Endocrinology & Metabolism 89, no. 6 (2004): 2963–72.

177 It can also increase blood triglycerides: Kimber L. Stanhope et al., “Consumption of Fructose and High Fructose Corn Syrup Increase Postprandial Triglycerides, LDL-Cholesterol, and Apolipoprotein-B in Young Men and Women,” Journal of Clinical Endocrinology & Metabolism 96, no. 10 (2011): E1596–E1605.

177 Estrogen may blunt some of these effects: Caroline Couchepin et al., “Markedly Blunted Metabolic Effects of Fructose in Healthy Young Female Subjects Compared with Male Subjects.” Diabetes Care 31, no. 6 (2008): 1254–56.

177 male lab rats are more affected: T. J. Horton et al., “Female Rats Do Not Develop Sucrose-Induced Insulin Resistance,” American Journal of Physiology 272, no. 5 (1997): R1571–R1576.

177 high triglyceride levels from high-fructose diets: Hara Estoff Marano, “The Trouble with Fructose,” Psychology Today, September/October 2012, 48.

178 medicine that could cause memory loss: Leslie R. Wagstaff et al., “Statin-Associated Memory Loss: Analysis of 60 Case Reports and Review of the Literature,” Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy 23, no. 7 (2003): 871–880.

178 increased blood-sugar levels, muscle damage: Giuseppe Caso et al., “Effect of Coenzyme Q10 on Myopathic Symptoms in Patients Treated with Statins,” American Journal of Cardiology 99, no. 10 (2007): 1409–12; Beatrice A. Golomb and Marcella A. Evans, “Statin Adverse Effects,” American Journal of Cardiovascular Drugs 8, no. 6 (2008): 373–418.

178 tingling and numbness in your extremities: Y. L. Lo et al., “Statin Therapy and Small Fiber Neuropathy: A Serial Electrophysiological Study,” Journal of the Neurological Sciences 208, no. 1 (2003): 105–8.

178 deplete key nutrients: Caso et al., “Effect of Coenzyme q10 on Myopathic Symptoms,” 1409–12.

178 eat more unhealthy foods: Rita F. Redberg and Mitchell H. Katz, “Healthy Men Should Not Take Statins,” JAMA 307, no. 14 (2012): 1491–92; Takehiro Sugiyama et al., “Different Time Trends of Caloric and Fat Intake Between Statin Users and Nonusers Among U.S. Adults: Gluttony in the Time of Statins?” JAMA Internal Medicine, April 24, 2014, pp. e1–e8.

178 eggs are a great source of protein: Maria Luz Fernandez, “Dietary Cholesterol Provided by Eggs and Plasma Lipoproteins in Healthy Populations,” Current Opinion in Clinical Nutrition & Metabolic Care 9, no. 1 (2006): 8–12; Christopher N. Blesso et al., “Whole Egg Consumption Improves Lipoprotein Profiles and Insulin Sensitivity to a Greater Extent Than Yolk-Free Egg Substitute in Individuals with Metabolic Syndrome,” Metabolism 62, no. 3 (2013): 400–410; Ying Rong et al., “Egg Consumption and Risk of Coronary Heart Disease and Stroke: Dose-Response Meta-analysis of Prospective Cohort Studies,” British Medical Journal 346 (2013): e8539.

178 eggs are high in choline: Kristin L. Herron and Maria Luz Fernandez, “Are the Current Dietary Guidelines Regarding Egg Consumption Appropriate?” Journal of Nutrition 134, no. 1 (2004): 187–90.

178 Many women aren’t getting enough choline: National Health and Nutrition Examination Survey (NHANES), 2005–2006 (ICPSR 25504), United States Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics.

178 low choline levels are associated with anxiety and depression: I. Bjelland et al., “Choline in Anxiety and Depression: The Hordaland Health Study” American Journal of Clinical Nutrition 90, no. 4 (2009): 1056–60.

178 Eat eggs: Choline may be particularly crucial during pregnancy; mothers given choline supplements during their second trimester have babies with better brain function and less risk of schizophrenia.

179 giving diet drinks to research subjects: S. Fowler et al., “Diet Soft Drink Consumption Is Associated with Increased Incidence of Overweight and Obesity in the San Antonio Heart Study,” Diabetes 54 (2005): A258; R. Dhingra et al., “Soft Drink Consumption and Risk of Developing Cardiometabolic Risk Factors and the Metabolic Syndrome in Middle-Aged Adults in the Community,” Circulation 116 (2007): 480–88.

180 Rats given aspartame: Sharon P. Fowler et al., “Fueling the Obesity Epidemic? Artificially Sweetened Beverage Use and Long-term Weight Gain,” Obesity 16, no. 8 (2008): 1894–1900.

180 rats given saccharrine water: Anthony Sclafani and Steven Xenakis, “Sucrose and Polysaccharide Induced Obesity in the Rat,” Physiology & Behavior 32, no. 2 (1984): 169–74.

180 Indigenous cultures with no processed food: S. Lindeberg and B. Lundh, “Apparent Absence of Stroke and Ischaemic Heart Disease in a Traditional Melanesian Island: A Clinical Study in Kitava,” Journal of Internal Medicine 233, no. 3 (1993): 269–75; Ami K. Patel, Jack T. Rogers, and Xudong Huang, “Flavanols, Mild Cognitive Impairment, and Alzheimer’s Dementia,” International Journal of Clinical and Experimental Medicine 1, no. 2 (2008): 181.

181 Refined white flour and sugar: David Perlmutter, Grain Brain: The Surprising Truth About Wheat, Carbs, and Sugar—Your Brain’s Silent Killers (New York: Little, Brown and Company, 2013).

181 fatty red meats: Dorothy J. Pattison et al., “Dietary Risk Factors for the Development of Inflammatory Polyarthritis: Evidence for a Role of High Level of Red Meat Consumption,” Arthritis & Rheumatism 50, no. 12 (2004): 3804–12.

181 sweetened drinks: Lawrence De Koning et al., “Sweetened Beverage Consumption, Incident Coronary Heart Disease, and Biomarkers of Risk in Men,” Circulation 125, no. 14 (2012): 1735–41.

181 diet sodas: David S. Ludwig, “Artificially Sweetened Beverages: Cause for Concern,” JAMA 302, no. 22 (2009): 2477–78.

181 Ginger: Reinhard Grzanna et al., “Ginger—An Herbal Medicinal Product with Broad Anti-inflammatory Actions,” Journal of Medicinal Food 8, no. 2 (2005): 125–32.

181 and turmeric: Bharat B. Aggarwal and Kuzhuvelil B. Harikumar, “Potential Therapeutic Effects of Curcumin, the Anti-inflammatory Agent, Against Neurodegenerative, Cardiovascular, Pulmonary, Metabolic, Autoimmune and Neoplastic Diseases,” The International Journal of Biochemistry & Cell Biology 41, no. 1 (2009): 40–59.

181 catechins: George L. Tipoe et al., “Green Tea Polyphenols as an Anti-oxidant and Anti-inflammatory Agent for Cardiovascular Protection,” Cardiovascular & Hematological Disorders—Drug Targets (Formerly Current Drug Targets—Cardiovascular & Hematological Disorders) 7, no. 2 (2007): 135–44.

181 theaflavin: Rajesh Aneja et al., “Theaflavin, a Black Tea Extract, Is a Novel Anti-inflammatory Compound,” Critical Care Medicine 32, no. 10 (2004): 2097–2103.

181 Omega-3 fatty acids are antioxidants: Maria Skouroliakou et al., “A Double-Blind, Randomized Clinical Trial of the Effect of Omega-3 Fatty Acids on the Oxidative Stress of Preterm Neonates Fed Through Parenteral Nutrition,” European Journal of Clinical Nutrition 64, no. 9 (2010): 940–47.

181 lower inflammation: Philip C. Calder, “Omega-3 Polyunsaturated Fatty Acids, Inflammation, and Inflammatory Diseases,” American Journal of Clinical Nutrition 83, no. 6 (2006): S1505–S1519.

182 supplementation improves symptoms: Anxious patients are more deficient in eicosapentaenoic acid (EPA, an omega-3) than depressed patients, who have lower-than-normal levels, and those with more severe social anxiety disorders have lower omega-3 fatty acid levels than those with less severe ­symptoms. Omega-3 supplementation decreases anxiety-like behaviors in rodents, nonhuman primates, and medical students. One important caveat for taking omega-3 supplements: they need to be high in EPA, at least 60 percent, and lower in docosahexaenoic acid (DHA) to have beneficial effects on psychiatric complaints.

182 fish oils can be used to decrease impulsivity: B. Hallahan and M. R. Garland, “Essential Fatty Acids and Their Role in the Treatment of Impulsivity Disorders,” Prostaglandins Leukot Essen. Fatty Acids 71, no. 4 (2004): 211–16; Alexandra J. Richardson, “Omega-3 Fatty Acids in ADHD and Related Neurodevelopmental Disorders,” International Review of Psychiatry 18, no. 2 (2006): 155–72; Jerome Sarris, et al., “Omega-3 for Bipolar Disorder: Meta-analyses of Use in Mania and Bipolar Depression,” Journal of Clinical Psychiatry 73, no. 1 (2012): 81–86.

182 some schizophrenia symptoms: K. Akter et al., “A Review of the Possible Role of the Essential Fatty Acids and Fish Oils in the Etiology, Prevention or Pharmacotherapy of Schizophrenia,” Journal of Clinical Pharmacy and Therapeutics 37, no. 2 (2012): 132–39.

182 slow down telomere shortening: R. Farzaneh-Far et al., “Association of Marine Omega-3 Fatty Acid Levels with Telomeric Aging in Patients with Coronary Heart Disease,” JAMA 303 (2010): 250–57.

182 can form endocannabinoids: Iain Brown et al., “Cannabinoids and Omega-3/6 Endocannabinoids as Cell Death and Anticancer Modulators,” Progress in Lipid Research 52, no. 1 (2013): 80–109.

182 Hemp seeds: J. C. Callaway, “Hempseed as a Nutritional Resource: An Overview,” Euphytica 140, no. 1–2 (2004): 65–72.

182 my morning muesli: My mix: raw oats, chia seeds, flax seeds, hemp seeds, and sliced almonds, served with unsweetened almond milk and a splash of pure maple syrup from our woods, courtesy of Jeremy.

182 Trillions of bacteria in our GI systems: Hiroyuki Osawa et al., “Changes in Plasma Ghrelin Levels, Gastric Ghrelin Production, and Body Weight After Helicobacter Pylori Cure,” Journal of Gastroenterology 41, no. 10 (2006): 954–61.

182 How do you get a fat mouse thinner: Peter J. Turnbaugh et al., “Diet-Induced Obesity Is Linked to Marked but Reversible Alterations in the Mouse Distal Gut Microbiome,” Cell Host & Microbe 3, no. 4 (2008): 213–23.

182 Gut bacteria have a lot to do with obesity: John K. DiBaise et al., “Gut Microbiota and Its Possible Relationship with Obesity,” in Mayo Clinic Proceedings 83, no. 4 (2008): 460–69.

182 different levels of certain bacteria: R. Mathur et al., “Methane and Hydrogen Positivity on Breath Test Is Associated with Greater Body Mass Index and Body Fat,” Journal of Clinical Endocrinology & Metabolism 98, no. 4 (2013): E698–E702.

182 In humans given a lean donor’s microbes: Anne Vrieze et al., “Transfer of Intestinal Microbiota from Lean Donors Increases Insulin Sensitivity in Individuals with Metabolic Syndrome,” Gastroenterology 143, no. 4 (2012): 913–16.

182 Probiotics help stop the weight gain . . . (Zyprexa): K. J. Davey et al., “Antipsychotics and the Gut Microbiome: Olanzapine-Induced Metabolic Dysfunction Is Attenuated by Antibiotic Administration in the Rat,” Translational Psychiatry 3, no. 10 (2013): e309.

183 Smaller stomachs fill up more quickly: David E. Cummings et al., “Plasma Ghrelin Levels After Diet-Induced Weight Loss or Gastric Bypass Surgery,” New England Journal of Medicine 346, no. 21 (2002): 1623–30.

183 nonsurgical recipients also lost weight: Alice P. Liou et al., “Conserved Shifts in the Gut Microbiota Due to Gastric Bypass Reduce Host Weight and Adiposity,” Science of Translational Medicine 5, no. 178 (2013): 178.

183 Artificial sweeteners such as Splenda: Mohamed B. Abou-Donia et al., “Splenda Alters Gut Microflora and Increases Intestinal P-Glycoprotein and Cytochrome P-450 in Male Rats,” Journal of Toxicology and ­Environmental Health, Part A 71, no. 21 (2008): 1415–29.

183 deranging glucose: Jotham Suez et al. “Artificial Sweeteners Induce Glucose Intolerance by Altering the Gut Microbiota,” Nature, published online, September 17, 2014, doi:10.1038/Nature13793.

183 Probiotic supplements: Michael Pollan, “Some of My Best Friends Are Germs,” New York Times Magazine, May 15, 2013.

183 encourage weight loss: Nathalie M. Delzenne et al., “Targeting Gut Microbiota in Obesity: Effects of Prebiotics and Probiotics,” Nature Reviews Endocrinology 7, no. 11 (2011): 639–46.

183 Onions, artichokes, asparagus, and sunchokes: Roya Kelishadi et al., “A Randomized Triple-Masked Controlled Trial on the Effects of Synbiotics on Inflammation Markers in Overweight Children,” Jornal de Pediatria 90, no. 2 (2014): 161–67.

183 keep down inflammation: Typically, prebiotics come from plant fiber, but unlike any other living tissue, breasts make prebiotics. Breast milk is the best source of prebiotics for a baby, and actually the only source, unless you’re game to give a baby pureed Jerusalem artichokes and asparagus.

184 when gut microbes from easygoing, adventurous mice: Stephen M. Collins et al., “The Adoptive Transfer of Behavioral Phenotype Via the Intestinal Microbiota: Experimental Evidence and Clinical Implications,” Current Opinion in Microbiology 16, no. 3 (2013): 240–45.

184 In animal studies, LPS administration: M. Maes et al., “The Gut-Brain Barrier in Major Depression: Intestinal Mucosal Dysfunction with an Increased Translocation of LPS from Gram Negative Enterobacteria (Leaky Gut) Plays a Role in the Inflammatory Pathophysiology of Depression,” Neuro Endocrinology Letters 29, no. 1 (2008): 117–24.

184 A person’s immune response to LPS: Robert Dantzer et al., “From Inflammation to Sickness and Depression: When the Immune System Subjugates the Brain,” Nature Reviews Neuroscience 9, no. 1 (2008): 46–56.

184 cytokines associated with depression: Tumor necrosis factor alpha (TNF-alpha), IL-6, and IL-1beta.

184 Ingesting probiotics may improve depression: A. C. Logan and M. Katzman, “Major Depressive Disorder: Probiotics May Be an Adjuvant Therapy,” Medical Hypotheses 64, no. 3 (2005): 533–38.

184 By manipulating the bacteria found in the stomach: N. Sudo et al., “Postnatal Microbial Colonization Programs the Hypothalamic-Pitutary-Adrenal System for Stress Response in Mice,” Journal of Physiology 558 (2004): 263–75.

184 behavior can be altered: Chronic treatment with the bacteria Mycobacterium vaccae improves quality-­of-life scores by reducing levels of cytokines, thus lowering inflammation. Treatment with bifidobacteria increases brain levels of tryptophan, required for serotonin synthesis.

184 Treatment with probiotics lowers scores: M. Messaoudi et al., “Beneficial Psychological Effects of a Probiotic Formulation (Lactobacillus Helveticus R0052 and Bifidobacterium Longum R0175) in Healthy Human Volunteers,” Gut Microbes 2, no. 4 (July/August 2011): 256–61.

184 Women who eat probiotic yogurt: Kirsten Tillisch et al., “Consumption of Fermented Milk Product with Probiotic Modulates Brain Activity,” Gastroenterology 144, no. 7 (2013): 1394–140.

184 They affect GABA: Radhika Dhakal et al., “Production of Gaba (-Aminobutyric Acid) by ­Microorganisms: A Review,” Brazilian Journal of Microbiology 43, no. 4 (2012): 1230–41.

184–185 calm the nervous system: Lactobacillus creates more GABA receptors in the brain and produces the neurotransmitter itself in the gut.

185 junctions between the cells: Called desmosomes.

185 corkscrew shape: Families Spirochaetaceae and Spirillaceae.

186 Stress, obesity, poor diet, and a leaky gut: E. Haroon et al., “Psychoneuroimmunology Meets Neuropsychopharmacology: Translational Implications of the Impact of Inflammation on Behavior,” Neuropsychopharmacology 37, no. 1 (2012): 137–62.

186 proteins in gluten: Gliadins and glutenins.

187 gluteomorphin, which hits the endorphin receptors: William Davis, Wheat Belly: Lose the Wheat, Lose the Weight, and Find Your Path Back to Health (New York: Rodale, 2011).

188 Geneen Roth’s books: Breaking Free from Emotional Eating, Feeding the Hungry Heart, When Food Is Love, Appetites.

189 Slow, deep breathing through your nose: Ravinder Jerath et al., “Physiology of Long Pranayamic Breathing: Neural Respiratory Elements May Provide a Mechanism That Explains How Slow Deep Breathing Shifts the Autonomic Nervous System,” Medical Hypotheses 67, no. 3 (2006): 566–71.

189 Stress, whether physical or emotional: Donna L. Tempel and Sarah F. Leibowitz, “PVN Steroid Implants: Effect on Feeding Patterns and Macronutrient Selection,” Brain Research Bulletin 23, no. 6 (1989): 553–60; Rouach et al., “The Acute Ghrelin Response to a Psychological Stress Challenge,” 693–702; Cizza et al., “Low 24-hour Adiponectin and High Nocturnal Leptin Concentrations,” 1079–87.

190 a protein called peptide Y: G. Cizza et al., “Low 24-Hour Adiponectin and High Nocturnal Leptin Concentrations in a Case-Control Study of Community-Dwelling Premenopausal Women with Major Depressive Disorder: The Premenopausal, Osteopenia/Osteoporosis, Women, Alendronate, Depression (POWER) Study,” Journal of Clinical Psychiatry 71, no. 8 (2010): 1079–87.

190 Subordinate, bossed-around monkeys: V. Rouach et al., “The Acute Ghrelin Response to a Psychological Stress Challenge Does Not Predict the Post-stress Urge to Eat,” Psychoneuroendocrinology 32 (2007): 693–702.

190 Monkeys lower in the dominance hierarchy: M. E. Wilson et al., “Quantifying Food Intake in Socially Housed Monkeys: Social Status Effects on Caloric Consumption,” Physiology & Behavior 94, no. 4 (2008): 586–94.

190 Lower-ranked British civil servants: M. G. Marmot et al., “Health Inequalities Among British Civil The Whitehall II Study,” Lancet 337, no. 8754 (1991): 1387–93.

190 People who are more stressed out: Janet A. Tomiyama et al., “Comfort Food Is Comforting to Those Most Stressed: Evidence of the Chronic Stress Response Network in High Stress Women,” Psychoneuroendocrinology 36, no. 10 (2011): 1513–19.

190 reducing stress through meditation or yoga can help you lose weight: Jennifer Daubenmier et al., “Mindfulness Intervention for Stress Eating to Reduce Cortisol and Abdominal Fat Among Overweight and Obese Women: An Exploratory Randomized Controlled Study,” Journal of Obesity, article ID 651936 (2011).

190 high cortisol levels associated with stress cause higher blood sugar levels: Paul E. Marik and Rinaldo Bellomo, “Stress Hyperglycemia: An Essential Survival Response,” Critical Care 17, no. 2 (2013): 305.

192 food tastes best for the first few bites: Mary Abbott, “Taste: The Neglected Nutritional Factor,” Journal of the American Dietetic Association 97, no. 10 (1997): S205–S207.

193 intense feelings can affect our taste buds: Petra Platte et al., “Oral Perceptions of Fat and Taste Stimuli Are Modulated by Affect and Mood Induction,” PloS One 8, no. 6 (2013): e65006.

193 stressed-out monkeys lower in the dominance hierarchy: Wilson et al., “Quantifying Food Intake in Socially Housed Monkeys,” 586–94.

Chapter Nine: So Tired We’re Wired

195 Women are more sensitive: Michael Breus, The Sleep Doctor’s Diet Plan: Lose Weight Through Better Sleep (New York: Rodale, 2011).

195 Women are more prone to insomnia: Andrew D. Krystal, “Insomnia in Women,” Clinical Cornerstone 5, no. 3 (2003): 41–50.

195 three out of four insomnia patients: Medco Health Solutions, “America’s State of Mind Report,” ­November 2011.

195 Nearly 30 percent of American women: Fiona C. Baker et al., “Association of Sociodemographic, Lifestyle, and Health Factors with Sleep Quality and Daytime Sleepiness in Women: Findings from the 2007 National Sleep Foundation ‘Sleep in America Poll,’    ” Journal of Women’s Health 18, no. 6 (2009): 841–49.

196 When sleep is off-kilter: Edward C. Suarez, “Self-Reported Symptoms of Sleep Disturbance and Inflammation, Coagulation, Insulin Resistance and Psychosocial Distress: Evidence for Gender Disparity,” Brain, Behavior, and Immunity 22, no. 6 (2008): 960–68; Mary Amanda Dew et al., “Healthy Older Adults’ Sleep Predicts All-Cause Mortality at 4 to 19 Years of Follow-up,” Psycho­somatic Medicine 65, no. 1 (2003): 63–73; Swapnil N. Rajpathak, “Lifestyle Factors of People with Exceptional Longevity,” Journal of the American Geriatrics Society 59, no. 8 (August 2011): 1509–12.

196 Sleep deprivation: Endocannabinoids, the anti-inflammatory chemicals that mimic the phar­macological actions of cannabis, are likely essential factors in sleep promotion. Other sleep-

inducing molecules include orexin, pieces of proteins called peptides, various hormones, and pro- and anti-inflammatory cytokines.

196 Higher resting heart rates: Kylie J. Barnett, “The Effects of a Poor Night Sleep on Mood, Cognitive, ­Autonomic and Electrophysiological Measures,” Journal of Integrative Neuroscience 7, no. 03 (2008): 405–20.

196 Americans are sleep deprived: T. S. Wiley with Bent Formby, Lights Out: Sleep, Sugar, and Survival (New York: Simon and Schuster, 2000), 4.

196 lucky if we get seven: In the 1970s, we worked thirty-five hours a week and enjoyed twenty-seven hours of leisure time. Now it’s forty-eight and fifteen.

196 One-quarter of American adults report: Yinong Chong et al., “Prescription Sleep Aid Use Among Adults: United States, 2005–2010,” NCHS Data Brief 127 (2013): 1–8.

197 Chronic sleep deprivation does three things: Kristen L. Knutson et al., “The Metabolic Consequences of Sleep Deprivation,” Sleep Medicine Reviews 11, no. 3 (June 2007): 163–78.

197 Animal studies and human studies: A. V. Nedeltcheva et al., “Sleep Curtailment Is Accompanied by Increased Intake of Calories from Snacks,” American Journal of Clinical Nutrition 89 (2009): 126–33.

197 Obese research subjects show: J. E. Gangwisch et al., “Inadequate Sleep as a Risk Factor for Obesity: Analyses of the NHANES I,” Sleep 28, no. 10 (2005) 1289–96.

197 Chronic sleep deprivation: Mariana G. Figueiro et al., “Light Modulates Leptin and Ghrelin in Sleep-­Restricted Adults,” International Journal of Endocrinology 2012, article ID 530; S. Taheri et al., “Short Sleep Duration Is Associated with Reduced Leptin, Elevated Ghrelin, and Increased Body Mass Index,” PLoS Medicine 1 (2004): e62; P. Schüssler et al., “Nocturnal Ghrelin, ACTH, GH and Cortisol Secretion After Sleep Deprivation in Humans,” Psychoneuroendocrinology 31 (2006): 915–23.

197 Even a single night of sleep deprivation: S. M. Schmid et al., “A Single Night of Sleep Deprivation Increases Ghrelin Levels and Feelings of Hunger in Normal-Weight Healthy Men,” Journal of Sleep Research 17 (2008): 331–34.

197 Sleep deprivation has been linked: Karine Spiegel et al., “Sleep Loss: A Novel Risk Factor for Insulin Resistance and Type 2 Diabetes,” Journal of Applied Physiology 99, no. 5 (2005): 2008–19; H. K. Yaggi et al., “Sleep Duration as a Risk Factor for the Development of Type 2 Diabetes,” Diabetes Care 29 (2006): 657–61.

197 Less than one week of sleep restriction: N. T. Ayas et al., “A Prospective Study of Self-Reported Sleep ­Duration and Incident Diabetes in Women,” Diabetes Care 26 (2003): 380–84.

197 Sleep deprivation creates horrendous performance: Fulda and Schulz, “Cognitive Dysfunction in Sleep Disorders,” Sleep Medicine Reviews 15, no. 6 (2001): 423–45.

197 just over 4 percent of American drivers: Centers for Disease Control and Prevention, MMWR 61, no. 51 (January 4, 2013): 1033–37.

198 slow-wave sleep: Delta waves predominate here.

198 dreaming occurs: Except in children who have night terrors in slow-wave sleep.

199 the immune system uses sleep time: Lulu Xie et al., “Sleep Drives Metabolite Clearance from the Adult Brain,” Science 342, no. 6156 (2013): 373–77.

199 clean out debris: The space between brain cells in lab rats is 60 percent greater during sleep, enhancing spinal fluid flow by a factor of ten.

199 proinflammatory state: Michael R. Irwin et al., “Sleep Loss Activates Cellular Inflammatory Signaling,” Biological Psychiatry 64, no. 6 (2008): 538–40.

199 alters microglia function: Mark R. Zielinski and James M. Krueger, “Sleep and Innate Immunity,” Frontiers in Bioscience (Scholar edition) 3 (2011): 632.

199 Sleep prevents seizures: Harinder Jaseja, “Purpose of REM Sleep: Endogenous Anti-epileptogenesis in Man—a Hypothesis,” Medical Hypotheses 62, no. 4 (2004): 546–48.

199 three-quarters of our sleep: In newborns, it’s 80 percent REM and 20 percent non-REM.

200 sleep deprivation: In depressive disorders, insomnia is often one of the first symptoms to appear, sometimes occurring before the onset of mood symptoms, while in anxiety disorders, insomnia comes after other symptoms.

200 Circadian manipulation and sleep deprivation: Thomas A. Wehr, “Improvement of Depression and Triggering of Mania by Sleep Deprivation,” JAMA 267, no. 4 (1992): 548–51; Blynn G. Bunney and William E. Bunney, “Mechanisms of Rapid Antidepressant Effects of Sleep Deprivation Therapy: Clock Genes and Circadian Rhythms,” Biological Psychiatry 73, no. 12 (2013): 1164–71.

200 Using bright light in the morning: Michael Terman and Jiuan Su Terman, “Bright Light Therapy: Side Effects and Benefits Across the Symptom Spectrum,” Journal of Clinical Psychiatry 60, no. 11 (1999): 799–808.

201 Both slow-wave sleep and REM-phase sleep: Jutta Backhaus et al., “Midlife Decline in Declarative Memory Consolidation Is Correlated with a Decline in Slow Wave Sleep,” Learning & Memory 14, no. 5 (2007): 336–41; Susanne Diekelmann and Jan Born, “The Memory Function of Sleep,” Nature Reviews Neuroscience 11, no. 2 (2010): 114–26.

201 As much as a ninety-minute nap: Matthew P. Walker and Robert Stickgold, “Overnight Alchemy: Sleep-Dependent Memory Evolution,” Nature Reviews Neuroscience 11, no. 3 (2010): 218–218.

201 Losing sleep repeatedly: S. Fulda and H. Schulz, “Cognitive Dysfunction in Sleep Disorders,” Sleep Medicine Reviews 5, no. 6 (2001): 423–45.

201 One study showed that 100 percent of children with an ADHD: N. Golan et al., “Sleep Disorders and Daytime Sleepiness in Children with Attention-Deficit/Hyperactive Disorder,” Sleep 27, no. 2 (2004): 261–66.

202 Half the children undergoing tonsillectomies: R. D. Chervin et al., “Sleep-Disordered Breathing, Behavior, and Cognition in Children Before and After Adenotonsillectomy,” Pediatrics 117 (2006): 769–78.

202 Our body cycles over the course: D. J. Brambilla et al., “The Effect of Diurnal Variation on Clinical Measurement of Serum Testosterone and Other Sex Hormone Levels in Men.” Journal of Clinical Endocrinology and Metabolism 94 (2009): 907–13.

202 nighttime breast milk has more compounds: Williams, Breasts.

203 Melatonin: Melatonin has a reputation as being an antiaging supplement. Consuming melatonin may neutralize oxidative damage and delay the neurodegenerative process of aging. D. Acuña-Castroviejo et al., “Melatonin, Mitochondria, and Cellular Bioenergetics,” Journal of Pineal Research 30, no. 2 (March 2001): 65–74; M. Pohanka, “Alzheimer’s Disease and Related Neurodegenerative Disorders: Implication and Counteracting of Melatonin,” Journal of Applied Biomedicine 9 (2011): 185–96.

203 Healthy serotonin levels: Gregory M. Cahill and Joseph C. Besharse, “Circadian Regulation of Melatonin in the Retina of Xenopus Laevis: Limitation by Serotonin Availability,” Journal of Neurochemistry 54, no. 2 (1990): 716–19; Venkataramanujan Srinivasan et al., “Melatonin in Mood Disorders,” World Journal of Biological Psychiatry 7, no. 3 (2006): 138–51.

203 jet lag: Here’s how to treat jet lag: Take 3 milligrams of melatonin between ten P.M. and eleven P.M. for three nights when you first arrive at your destination. When you return home, again, take 3 milligrams for three nights between ten P.M. and eleven P.M. Easy. And it makes a huge difference. Please note that 3 milligrams is not what is typically used for sleep. Melatonin for sleep should still be taken bewteen ten P.M. and eleven P.M., but it’s wiser to use half a milligram or 1 milligram in this case.

203 Breast cancer has been linked: R. G. Stevens, “Light-at-Night, Circadian Disruption and Breast Cancer: Assessment of Existing Evidence,” International Journal of Epidemiology 38 (2009): 963–70.

203 women who are blind: E. E. Flynn-Evans et al., “Total Visual Blindness Is Protective Against Breast ­Cancer,” Cancer Causes and Control 20 (2009): 1753–56.

203 Sleeping in a dark room: D. E. Blask, “Melatonin, Sleep Disturbance and Cancer Risk,” Sleep Medicine Reviews 13 (2008): 257–64.

204 In seasonal-breeding mammals: Dorota A. Zieba et al., “In Vitro Evidence That Leptin Suppresses Melatonin Secretion During Long Days and Stimulates Its Secretion During Short Days in Seasonal Breeding Ewes,” Domestic Animal Endocrinology 33, no. 3 (2007): 358–65.

204 Rising ghrelin levels: B. O. Yildiz et al., “Alterations in the Dynamics of Circulating Ghrelin, Adiponectin, and Leptin in Human Obesity,” PNAS 101 (2004): 10434–39.

204 Melatonin may enhance: M. I. Alonso-Vale et al., “Melatonin Enhances Leptin Expression by Rat Adipocytes in the Presence of Insulin,” Am J Physiol Endocrinol Metab 288, no. 4 (April 2005): E805–E812.

204–205 In lab rats fed high-calorie diets: María J. Ríos-Lugo et al., “Melatonin Effect on Plasma Adiponectin, Leptin, Insulin, Glucose, Triglycerides and Cholesterol in Normal and High Fat–Fed Rats,” Journal of ­Pineal Research 49, no. 4 (2010): 342–48.

205 Sleep deprivation is associated: G. Copinschi, “Metabolic and Endocrine Effects of Sleep Deprivation,” Essential Psychopharmacology 6, no. 6 (2005): 341–47.

205 Women with lower levels of melatonin: C. J. McMullan et al., “Melatonin Secretion and the Incidence of Type 2 Diabetes,” JAMA 309, no. 13 (April 2013): 1388–96.

205 Bright-light exposure: Mariana G. Figueiro et al., “Light Modulates Leptin and Ghrelin in Sleep-­Restricted Adults,” International Journal of Endocrinology 2012, article ID 530726.

205 A full night’s sleep: A. N. Vgontzas et al., “Adverse Effects of Modest Sleep Restriction on Sleepiness, Performance, and Inflammatory Cytokines,” J Clin Endocrinol Metab 89 (2004): 2119–26.

205 If you sleep less than seven hours: Sheldon Cohen et al., “Sleep Habits and Susceptibility to the Common Cold,” Archives of Internal Medicine 169, no. 1 (2009): 62.

207 Estrogen, in particular, is involved: Yuki Tsuchiya et al., “Cytochrome P450-Mediated Metabolism of Estrogens and Its Regulation in Humans,” Cancer Letters 227 (2005) 115–24.

207 Caffeine triggers adrenaline: Stuart R. Snider and Bertil Waldeck, “Increased Synthesis of Adrenomedullary Catecholamines Induced by Caffeine and Theophylline,” Naunyn-Schmiedeberg’s Archives of Pharmacology 281, no. 2 (1974): 257–60; William R. Lovallo et al., “Caffeine Stimulation of Cortisol Secretion Across the Waking Hours in Relation to Caffeine Intake Levels,” Psychosomatic Medicine 67, no. 5 (2005): 734–39.

207 It also reduces REM sleep: Hans-Peter Landolt et al., “Caffeine Intake (200 Mg) in the Morning Affects Human Sleep and EEG Power Spectra at Night,” Brain Research 675, no. 1 (1995): 67–74.

207 Caffeine constricts blood vessels: Stacey C. Sigmon et al., “Caffeine Withdrawal, Acute Effects, Tolerance, and Absence of Net Beneficial Effects of Chronic Administration: Cerebral Blood Flow Velocity, Quantitative EEG, and Subjective Effects,” Psychopharmacology 204, no. 4 (2009): 573–85.

207–208 Just two hours of iPad use: Mariana G. Figueiro et al., “The Impact of Light from Computer Monitors on Melatonin Levels in College Students,” Neuro Endocrinology Letters 32, no. 2

(2011): 158.

208 two hours of computer use: Christian Cajochen et al., “Evening Exposure to a Light-Emitting Diodes (LED)-Backlit Computer Screen Affects Circadian Physiology and Cognitive Performance,” Journal of Applied Physiology 110, no. 5 (2011): 1432–38.

208 no glowing screens at least one hour: Andrew B. Dollins et al., “Effects of Illumination on Human Nocturnal Serum Melatonin Levels and Performance,” Physiology & Behavior 53, no. 1 (1993): 153–60; Mariana G. Figueiro et al., “The Impact of Light from Computer Monitors on Melatonin Levels in College Students,” Neuro Endocrinology Letters 32, no. 2 (2011): 158.

208 Even electronic readers can shift your circadian rhythm signals: A. Chang et al., “Impact of Evening Use of Light-Emitting Electronic Readers on Circadian Timing and Sleep Latency,” SLEEP 35, abstract supplement (2012): A205.

208 program called flux: Free download here: http://stereopsis.com/flux/research.html.

208 circadian receptors: http://www.blueblocker.com.

208 Blue blockers can significantly improve sleep: K. Burkhart and J. R. Phelps, “Amber Lenses to Block Blue Light and Improve Sleep: A Randomized Trial,” Chronobiology International 26, no. 8 (2009):1602–12.

208 Listen to music: Marconi Union’s eight-minute, trance-inducing tune “Weightless,” at sixty beats per minute, is a good place to start.

208 Write in your journal: Ting Zhang et al., “A ‘Present’ for the Future: The Unexpected Value of Rediscovery,” Psychological Science (2014): 0956797614542274.

208 Gratitude is good for your mood: Andrew Weil, Spontaneous Happiness (Little, Brown and Company, 2011).

209 Well-timed sleep deprivation: Burkhard Pflug, “The Effect of Sleep Deprivation on Depressed Patients,” Acta Psychiatrica Scandinavica 53, no. 2 (1976): 148–58; D. A. Sack et al., “The Timing and Duration of Sleep in Partial Sleep Deprivation Therapy of Depression,” Acta Psychiatrica Scandinavica 77, no. 2 (1988): 219–24.

210 Women need lower doses: David J. Greenblatt et al., “Gender Differences in Pharmacokinetics and Pharmacodynamics of Zolpidem Following Sublingual Administration,” Journal of Clinical Pharmacology 54, no. 3 (2014): 282–90.

211 dementia: John Elwood Gallacher et al., “Benzodiazepine Use and Risk of Dementia: Evidence from the Caerphilly Prospective Study (CaPS),” J Epidemiology and Community Health 66 (2012): 869–73.

211 five-fold increase in early death: Daniel F. Kripke et al., “Hypnotics’ Association with Mortality or Cancer: A Matched Cohort Study,” British Medical Journal Open 2, no. 1 (2012).

212 Alcohol might help you pass out: Timothy Roehrs and Thomas Roth, “Sleep, Sleepiness, and Alcohol Use,” Alcohol Research and Health 25, no. 2 (2001): 101–9.

212 Even low doses of alcohol: Pierce Geoghegan et al., “Investigation of the Effects of Alcohol on Sleep Using Actigraphy,” Alcohol and Alcoholism 47, no. 5 (2012): 538–44.

212 can also worsen sleep apnea: Lawrence Scrima et al., “Increased Severity of Obstructive Sleep Apnea After Bedtime Alcohol Ingestion: Diagnostic Potential and Proposed Mechanism of Action,” Sleep: Journal of Sleep Research & Sleep Medicine 5, no. 4 (1982): 318–28.

212 Alcohol also delays and suppresses: Irshaad O. Ebrahim et al., “Alcohol and Sleep I: Effects on Normal Sleep,” Alcoholism: Clinical and Experimental Research 37, no. 4 (2013): 539–49.

213 homeopathic remedies: Deep Sleep by Herbs, Etc., Somnipure by Peak Life, and Quietude by Boiron are three I like.

Chapter Ten: A Sex Guide That Actually Works

215 Good sex . . . helps you destress: Stuart Brody, “Blood Pressure Reactivity to Stress Is Better for People Who Recently Had Penile–Vaginal Intercourse Than for People Who Had Other or No Sexual Activity,” Biological Psychology 71, no. 2 (2006): 214–22.

215 risk of heart disease: Susan A. Hall et al., “Sexual Activity, Erectile Dysfunction, and Incident Cardiovascular Events,” American Journal of Cardiology 105, no. 2 (2010): 192–97.

215 stimulates your immune system: Carl J. Charnetski and Francis X. Brennan, “Sexual Frequency and Salivary Immunoglobulin A (IgA),” Psychological Reports 94, no. 3 (2004): 839–44.

216 43 percent of women have complaints: Edward O. Laumann et al., “Sexual Dysfunction in the United States,” JAMA 281, no. 6 (1999): 537–44.

216 sexual dysfunction: Medically, there are four categories of female sexual dysfunction: hypoactive sexual ­desire disorder (not thinking horny thoughts or wanting sex); sexual arousal disorder (not responding fully to sexual stimulation); sexual pain disorders, like dyspareunia (pain ­during intercourse) and vaginismus (muscle spasms during stimulation); and orgasmic disorder (not climaxing).

216 higher cortisol levels that inhibit: Lisa Dawn Hamilton et al., “Cortisol, Sexual Arousal, and Affect in Response to Sexual Stimuli,” Journal of Sexual Medicine 5, no. 9 (2008): 2111–18.

216 restrict circulation: Diabetes, high cholesterol, cigarette smoking, crushed arteries from chronic bicycle riding, pelvic surgery, or sexual trauma.

216 a medication like Viagra: L. A. Berman et al., “Efficacy and Tolerability of Viagra (Sildenafil Citrate) in Women with Sexual Arousal Disorder: A Double-Blind, Placebo-Controlled Study,” Int J Impot Res 14, no. 3 (2002): S27–S28.

218 this stress and anxiety jams: Berman and Berman, For Women Only.

218–219 antidepressants that enhance serotonin levels: Parks W. Walker et al., “Improvement in ­Fluoxetine-Associated Sexual Dysfunction in Patients Switched to Bupropion,” Journal of Clinical Psychiatry (1993); Charles C. Coleman et al., “Sexual Dysfunction Associated with the Treatment of Depression: A Placebo-Controlled Comparison of Bupropion Sustained Release and Sertraline Treatment,” Annals of Clinical Psychiatry 11, no. 4 (1999): 205–15.

219 Some SSRIs: Zoloft and Paxil have reputations as significant disrupters of sexual pleasure. Lexapro, in my experience, has less impact on sexual functioning than some of the other antidepressants, and there is a new medication, dubbed Viibryd, that seems to have even fewer sexual side effects than the others. (I know. The double i is pretty silly, but the potential side effects aren’t: nausea, insomnia, and diarrhea. Sometimes depression doesn’t seem so bad in comparison.) I have switched quite a few of my patients over from another SSRI to Lexapro or from Lexapro to Viibryd, and they do report that it’s easier for them to achieve orgasm.

220 diminish libido: Lactation (nursing) and antipsychotics can also raise prolactin levels, killing sexual ­desire.

220 Prolactin is likely part of the negative feedback mechanism: Tillmann H. C. Krüger et al., “Orgasm-Induced Prolactin Secretion: Feedback Control of Sexual Drive?” Neuroscience & Biobehavioral Reviews 26, no. 1 (2002): 31–44.

220 sex act: SSRIs are often used to treat paraphilias or sexual fetishes, eliminating behaviors that are bothersome to patients or their communities.

220 In laboratory animals, the SSRI fluoxetine: N. Maswood et al., “Modest Effects of Repeated Fluoxetine on Estrous Cyclicity and Sexual Behavior in Sprague-Dawley Female Rats,” Brain Research 1245 (2008): 52–60.

220 Sex researcher Jim Pfaus explains: James G. Pfaus, “Reviews: Pathways of Sexual Desire,” Journal of Sexual Medicine 6, no. 6 (2009): 1506–33.

220 sex holiday: For my patients, I often recommend that they take their antidepressants five days out of the week, Sunday through Thursday. This will allow sexual side effects to diminish by Saturday night and Sunday morning, prime sex time for those who work weekdays. Studies find no increased depressive symptoms with this schedule. Brian E. Moore and Anthony J. Rothschild, “Treatment of Antidepressant-Induced Sexual Dysfunction,” Hospital Practice 34, no. 1 (1999): 89–91; Matthew J. Taylor et al., “Strategies for Managing Antidepressant-Induced Sexual Dysfunction: Systematic Review of Randomized Controlled Trials,” Journal of Affective Disorders 88, no. 3 (2005): 241–54.

221 sexual side effects: It is likely the most common combination in all of psychiatry for this reason. They also happen to work very nicely together, sort of like peanut butter and jelly. Between the two of them, they create one kick-ass antidepressant, because they cover most of the neurotransmitters that are implicated in depression. In the seventies and eighties, tricyclic antidepressants were used to combat anxiety and depression. They enhanced transmission of serotonin, norepinephrine, and dopamine, and they worked well, but the side effects were unbearable for many. Combining an SSRI with Wellbutrin mimics these old tricyclics, hitting the same trifecta of neurotransmitters, but without the dry mouth, constipation, and sedation of the old days. So why not just take Wellbutrin alone? I find that it’s great for a low-energy, low-motivation depression, but it’s not that good for anxiety symptoms or if you have a “short fuse.”

221 for a select few: There are a lot of women out there with the variant of the serotonin transporter gene (called SERT, where the SSRIs dock) that can make them more susceptible to the double whammy. If you are on SSRIs and have the genotype of two long genes (double-L), you’re nearly eight times more likely to have trouble with sexual dysfunction when oral contraceptives are added. Double-SERT people are more likely to be seasonal in their symptoms and tend to be better responders to SSRIs than double-S people, who tend to be more ­depressed than double-L people. So if you’re really having trouble with sexual side effects, please consider slowly tapering off your antidepressant altogether, with the help of your psychiatrist. You may be able to treat your depression in other ways, especially with phototherapy in the fall and winter if you’re a seasonally responsive double L. Or try a nonhormonal type of birth control if you can’t successfully taper.

222 In rats given an opioid receptor blocker: Tracy K. McIntosh et al., “Effects of Morphine, B-Endorphin and Naloxone on Catecholamine Levels and Sexual Behavior in the Male Rat,” Pharmacology Biochemistry and Behavior 13, no. 3 (1980): 435–41.

222 blunting sensations: In experiments, THC led to delayed time in both erection and ejaculation in men. In the female rat, levels of brain endocannabinoids are lowest during estrus (their peak of sexual responsiveness and fertility) and higher during other parts of their cycle. Female rats receiving an endocannabinoid antagonist, blocking the cannabinoid receptors, had increased signs of sexual motivation, suggesting that these may be potential medications for boosting low desire in women.

223 Cannabis can help you: Barbara Lewis, The Sexual Power of Marijuana (New York: P. H. Wyden., 1970); Frank H. Gawin, “Pharmacologic Enhancement of the Erotic: Implications of an Expanded Definition of Aphrodisiacs,” Journal of Sex Research 14, no. 2 (1978): 107–17.

223 In a study of five hundred women: Robert C. Kolodny et al., Textbook of Sexual Medicine (Boston: Little, Brown, 1979).

223 Women are more consistent: Boris B. Gorzalka et al., “Male–Female Differences in the Effects of Cannabinoids on Sexual Behavior and Gonadal Hormone Function,” Hormones and Behavior 58, no. 1 (2010): 91–99.

224 Grooves get laid down: Researchers have known for decades that if you stimulate pleasure centers chemically or electrically, the learned behavior is reinforced. The dopamine and endorphin release that accompanies arousal and orgasm will further reinforce this computer-linked behavior.

224 Most concerning is that oxytocin: William Struthers, Wired for Intimacy: How Pornography Hijacks the Male Brain (Westmont, IL: Intervarsity Press, 2009).

225 no longer do it for them: Sociology researcher Philip Zimbardo, in his article “The Demise of Guys,” describes a syndrome of arousal addiction that looks a bit like many of the conditions I treat in my ­office, incorporating aspects of ADHD, social anxiety disorder, depression, performance anxiety, and OCD. Philip Zimbardo and Nikita Duncan, “    ‘The Demise of Guys’: How Video Games and Porn Are Ruining a Generation,” CNN News, 2012.

225 “their appetite for porn”: Doidge, The Brain That Changes Itself, 131.

227 external portion of the clitoris: We all start out as girls in the womb before the testosterone surge makes the male parts. Penises are like oversized clitorises made large by testosterone. When women are given testosterone, enlarged clitorises, called clitoromegaly, can result.

227 The glans of the clitoris: Helen E. O’Connell et al., “Anatomical Relationship Between Urethra and Clitoris,” Journal of Urology 159, no. 6 (1998): 1892–97; Helen E. O’Connell et al., “Anatomy of the Clitoris,” Journal of Urology 174, no. 4 (2005): 1189–95.

227 clitoral body: See http://www.ericsbinaryworld.com/tag/clitoris/.

227 Spread clitoracy: Unfortunately, this is an uphill battle. Detailed accurate representations of female genitals are hard to come by. Even some recent textbooks of anatomy do not include the clitoris in diagrams of the female pelvis. R. S. Snell, Clinical Anatomy for Medical Students, 3rd ed. (London: Little, Brown and Co., 1986); P. L. Williams, Grays Anatomy: The Anatomical Basis of Medicine and Surgery, 38th ed. (Edinburgh: Churchill Livingstone, 1996).

227 unique genitals: See http://www.webburgr.com/400-vaginas-wall/.

228 orgasmic meditation: Nicole Daedone, Slow Sex: The Art and Craft of the Female Orgasm (New York: Hachette, 2011).

228 Some women see themselves as attracted to: Lisa M. Diamond, Sexual Fluidity: Understanding Women’s Love and Desire (Cambridge, MA: Harvard University Press, 2009).

228 Of self-identified straight women: Qazi Rahman and Glenn D. Wilson, “Born Gay? The Psychobiology of Human Sexual Orientation,” Personality and Individual Differences 34, no. 8 (2003): 1337–82.

228 evolution has favored women: Barry X. Kuhle and Sarah Radtke, “Born Both Ways: The Alloparenting Hypothesis for Sexual Fluidity in Women,” Evolutionary Psychology 11, no. 2 (2013).

229 Women gaze just as long at porn: Heather A. Rupp and Kim Wallen, “Sex Differences in Viewing Sexual Stimuli: An Eye-Tracking Study in Men and Women,” Hormones and Behavior 51, no. 4 (2007): 524–33.

229 In studies measuring vaginal blood flow: Meredith L. Chivers et al., “A Sex Difference in the Specificity of Sexual Arousal,” Psychological Science 15, no. 11 (2004): 736–44.

229 “sparked or sustained by”: Bergner, What Do Women Want, 7.

229 In studies measuring women’s lubrication: Meredith L. Chivers et al., “Agreement of Self-Reported and Genital Measures of Sexual Arousal in Men and Women: A Meta-Analysis,” Archives of Sexual Behavior 39, no. 1 (2010): 5–56.

229 Women who are hooked up: Michele G. Alexander and Terri D. Fisher, “Truth and Consequences: Using the Bogus Pipeline to Examine Sex Differences in Self-Reported Sexuality,” Journal of Sex Research 40, no. 1 (2003): 27–35.

230 The number of women who admit: Joseph W. Critelli and Jenny M. Bivona, “Women’s Erotic Rape Fantasies: An Evaluation of Theory and Research,” Journal of Sex Research 45, no. 1 (2008): 57–70.

231 shape of a man’s penis: The flared glans creates suction, pulling previous sperm away from the cervix. Humans have a larger testes-to-body ratio than most primates, and the longest, thickest penises of any primate. The largest genitals are found in species where many males copulate with one female. The human testicular volume and libido are far beyond what’s needed for monogamous pairing, and having an external scrotum is associated with promiscuous mating. In a man’s semen, the later ejaculate contains enzymes that kill whatever sperm come after his. To insure against “poachers,” men create more sperm when they haven’t seen their partner for a few days, even if they have ejaculated in her absence.

231 From an evolutionary standpoint: Ibid.

232 bring about climax: Sympathetic nervous system.

232 sharing your fantasies: Talk with your partner specifically about what role-playing might consist of and what the dos and don’ts are. Sometimes a good place to start is by reversing traditional gender roles (you be the man and he the woman), or playing doctor, or trying the old cowboy/schoolmarm scenario. Another option is to experiment with blindfolds and loose knots.

232 first experience: Even babies in the womb touch themselves, and, though rare, orgasms have been ­observed in children, and even in infants as young as six months old.

233 female-friendly: Try these female-friendly Web sites: http://www.femalefriendlyporn.com, http://www.goodvibrationsvod.com/main.jhtml, http://www.hotmoviesforher.com.

233 “my success rate . . . has been zero”: Betty Dodson, Orgasms for Two: The Joy of Partner Sex (New York: Random House, 2002), 117.

234 according to Alfred Kinsey: Alfred Charles Kinsey et al., Sexual Behavior in the Human Male (Philadelphia: WB Saunders, 1948).

234 Masters and Johnson: William H. Masters and Virginia E. Johnson, Reproductive Biology Research Foundation, Human Sexual Response (New York: Little, Brown, 1966).

235 Women shown porn after exercise: Cindy M. Meston and Manuel Worcel, “The Effects of Yohimbine Plus L-Arginine Glutamate on Sexual Arousal in Postmenopausal Women with Sexual Arousal Disorder,” Archives of Sexual Behavior 31, no. 4 (2002): 323–32.

235 Frequent exercise is one strategy: Tierney A. Lorenz and Cindy M. Meston, “Acute Exercise Improves Physical Sexual Arousal in Women Taking Antidepressants,” Annals of Behavioral Medicine 43, no. 3 (2012): 352–61.

235 exercise-induced orgasm: Sexual pleasure from exercise that doesn’t lead to orgasm is more often seen in biking or spinning classes as well as abdominal work and weight lifting.

235 Women reported more frequent and earlier-timed orgasms: David A. Puts et al., “Men’s Masculinity and Attractiveness Predict Their Female Partners’ Reported Orgasm Frequency and Timing,” Evolution and Human Behavior 33, no. 1 (2012): 1–9.

235 pelvic floor: See medicalartlibrary.com/pelvic-floor-muscles.html.

236 Kegelcizer: Dodsonandross.com.

236 “hysterical paroxysms” in women: Maines, The Technology of Orgasm.

237 heavily influenced by hormonal factors: J. E. Robinson and R. V. Short, “Changes in Breast Sensitivity at Puberty, During the Menstrual Cycle, and at Parturition,” British Medical Journal 1, no. 6070 (1977): 1188.

237 Nursing women are often much less sexually aroused: Melissa D. Avery et al., “The Experience of Sexuality During Breastfeeding Among Primiparous Women,” Journal of Midwifery & Women’s Health 45, no. 3 (2000): 227–37.

238 coital alignment technique: E. W. Eichel et al., “The Technique of Coital Alignment and Its Relation to Female Orgasmic Response and Simultaneous Orgasm,” Journal of Sex & Marital Therapy 14, no. 2 (Summer 1988): 129–41.

238 contact with your clitoris: There are YouTube videos of fully clothed people or cartoons to show you the ­details.

240 peters out: There has been fascinating research on just how the uterus contracts, how the cervix dips down to suck the semen into the opening, and then how the semen is directed toward the fallopian tube where the most mature egg is located. This activity is all mediated by oxytocin, the hormone that is released after orgasm and causes uterine contractions in childbirth, as well as prosocial, trusting behaviors.

240 Freud was a thirty-year-old virgin: Ryan and Jethá, Sex at Dawn.

240 Masters and Johnson determined: Masters and Johnson, Human Sexual Response.

240 different types of orgasm: Other researchers feel that since the G-spot is the back side of the clitoris, called the root, this is still a clitoral orgasm.

240 a “pelvic floor” orgasm: Berman and Berman, For Women Only.

240 toe sucking: See Barry Kamisurak and Beverly Whipple, “Non-genital Orgasms,” Sexual and Relationship Theory 26, no. 4 (2011): 356–72.

240 orgasm even after their spinal cord has been severed: Barry R. Komisaruk et al., “Brain Activation ­During Vaginocervical Self-Stimulation and Orgasm in Women with Complete Spinal Cord Injury: fMRI Evidence of Mediation by the Vagus Nerves,” Brain Research 1024, no. 1 (2004): 77–88.

240 can climax from nipple stimulation: Barry R. Komisaruk and Beverly Whipple, “Non-Genital Orgasms,” Sexual and Relationship Therapy 26, no. 4 (2011): 356–72.

240 can orgasm simply from thinking about their breasts: Beverly Whipple et al., “Physiological Correlates of Imagery-Induced Orgasm in Women,” Archives of Sexual Behavior 21, no. 2 (1992): 121–33.

240 the Kinsey study put the rate: A. Kinsey et al., Sexual Behavior in the Human Female (Philadelphia: Saunders, 1953).

240 spontaneous orgasms: Smaller surveys have placed the number higher, at 64 percent. Gina Ogden, “I’ll Have What She’s Thinking,” New York Times, September 29, 2013.

241 Two researchers put the number: Kinsey et al., Sexual Behavior in the Human Female; Barbara L. Wells, “Predictors of Female Nocturnal Orgasms: A Multivariate Analysis,” Journal of Sex Research 22, no. 4 (1986): 421–37; G. Winokur et al., “Nocturnal Orgasm in Women: Its Relation to Psychiatric Illness, Dreams, and Developmental and Sexual Factors,” Archives of General Psychiatry 1, no. 2 (1959): 180; Comradge L. Henton, “Nocturnal Orgasm in College Women: Its Relation to Dreams and Anxiety Associated with Sexual Factors,” Journal of Genetic Psychology 129, no. 2 (1976): 245–51.

241 The G-spot is more like: A. Kilchevsky et al., “Is the Female G-Spot Truly a Distinct Anatomic Entity?” Journal of Sexual Medicine 2011, no. 3 (January 2012): 719–26.

241 Zone: YouTube has a video called “G-Spot Stimulation” that is helpful: https://www.youtube.com/watch?v=hwJElbadlK0.

242 The MRI data comparing clitoral versus G-spot: B. R. Komisaruk et al., “An fMRI Time-Course Analysis of Brain Regions Activated During Self-Stimulation to Orgasm in Women,” Society for Neuroscience, 285 no. 6. (2010).

242 rear entry: Seeing enough spots yet? There’s more: the U-spot is south of the clitoris and north of the urethra. There is plenty of erectile tissue surrounding the urethra, but it is above the urethral opening and on either side of it. The urethra itself, and the area between the urethra and the vagina, doesn’t have the same pleasurable feel when stroked, so make sure you’re in the right neighborhood when searching for this spot. The U-spot is best stimulated gently and wetly. Pressure typically is less pleasurable.

242 cervical tapping: Winnifred B. Cutler, Love Cycles: The Science of Intimacy (Philadelphia: Athena Institute, 1996).

243 Lubricated condoms: Please note that most latex condoms will break down with petroleum-based lubricants like Vaseline. Water-based lubes are safest with condoms.

243 Weekly sex can help women: Winnifred B. Cutler et al., “Sexual Behavior Frequency and Menstrual Cycle Length in Mature Premenopausal Women,” Psychoneuroendocrinology 4, no. 4 (1979): 297–309.

244 It contains endorphins: Burt Sharp and A. Eugene Pekary, “β-Endorphin61–91 and Other β-Endorphin-Immunoreactive Peptides in Human Semen,” Journal of Clinical Endocrinology & Metabolism 52, no. 3 (1981): 586–88.

244 college women’s condom use: G. Gordon Jr. et al., “Does Semen Have Antidepressant Properties?” ­Archives of Sexual Behavior 31, no. 3 (2002): 289–93.

Chapter Eleven: Your Body: Love It or Leave It

245 increasingly sedentary lifestyles: Harold W. Kohl et al., “The Pandemic of Physical Inactivity: Global Action for Public Health,” Lancet (2012). 380, no. 9838 (2012): 294–305.

245 Inactivity taxes the body: I-Min Lee et al., “Effect of Physical Inactivity on Major Non-Communicable Diseases Worldwide: An Analysis of Burden of Disease and Life Expectancy,” Lancet 380, no. 9838 (2012): 219-29.

246 childhood fitness declined: J. Gahche et al., “Cardiorespiratory Fitness Levels Among U.S. Youth Aged 12–15 Years: United States, 1999–2004 and 2012.” NCHS Data Brief 153 (2014): 1–8.

246 Centers for Disease Control recommends: Centers for Disease Control and Prevention, “Adult Participation in Aerobic and Muscle-Strengthening Physical Activities—United States, 2011,” MMWR 62, no. 17 (2013): 326.

246 Exercise helps to prevent: Harmon Eyre et al., “Preventing Cancer, Cardiovascular Disease, and Diabetes: A Common Agenda for the American Cancer Society, the American Diabetes Association, and the American Heart Association,” CA: A Cancer Journal for Clinicians 54, no. 4 (2004): 190–207; Ming Kai et al., “Exercise Interventions: Defusing the World’s Osteoporosis Time Bomb,” Bulletin of the World Health Organization 81, no. 11 (2003): 827–30.

246 Cardiorespiratory fitness: Steven N. Blair and Suzanne Brodney, “Effects of Physical Inactivity and Obesity on Morbidity and Mortality: Current Evidence and Research Issues,” Medicine and Science in Sports and Exercise 31 (1999): S646–S662.

246 cardio can release endorphins: P. Hoffman, “The Endorphin Hypothesis,” in Physical Activity and Mental Health, ed. W. P. Morgan (Washington, DC: Taylor & Francis, 1997), 161–77.

246 improves levels of serotonin: F. Chaouloff, “The Serotonin Hypothesis,” in Morgan, Physical Activity and Mental Health.

246 dopamine: A. A. Bove et al., “Increased Conjugated Dopamine in Plasma After Exercise Training,” Journal of Laboratory and Clinical Medicine 104, no. 1 (1984): 77–85.

246 norepinephrine: R. K. Dishman, “The Norepinephrine Hypothesis,” in Morgan, Physical Activity and Mental Health, 1997.

246 Moderate aerobic: P. Salmon, “Effects of Physical Exercise on Anxiety, Depression, and Sensitivity to Stress: A Unifying Theory,” Clinical Psychology Review 21 (2001): 33–61; Chad D. Rethorst et al., “The Antidepressive Effects of Exercise,” Sports Medicine 39, no. 6 (2009): 491–511.

247 cognition, focuses attention: P. D. Tomporowski, “Effects of Acute Bouts of Exercise on Cognition,” Acta Psychologica 112, 297–324.

247 enhances wellbeing: D. Scully et al., “Physical Exercise and Psychological Well Being: A Critical Review,” British Journal of Sports Medicine 32 (1998): 111–20.

247 reverse or forestall aging effects: Zsolt Radak et al., “Exercise and Hormesis: Oxidative Stress-Related Adaptation for Successful Aging,” Biogerontology 6, no. 1 (2005): 71–75; John J. Ratey with Eric Hagerman, Spark: The Revolutionary New Science of Exercise and the Brain (Little, Brown and Company, 2008).

247 effects of hormonal fluctuations: Jennifer Lange-Collett and Lorna Schumann, “Promoting Health Among Perimenopausal Women Through Diet and Exercise,” Journal of the American Academy of Nurse Practitioners 14, no. 4 (2002): 172–79; J. E. Jurkowski et al., “Ovarian Hormonal Responses to Exercise,” Journal of Applied Physiology 44, no. 1 (1978): 109–14.

247 Exercising immediately before sex: Tierney Ahrold Lorenz and Cindy May Meston, “Exercise Improves Sexual Function in Women Taking Antidepressants: Results from a Randomized Crossover Trial,” Depression and Anxiety 99 (2013): 1–8.

247 Scheduling regular exercise before sex: Ibid.

247 exercise fosters this plasticity: Ratey with Hagerman, Spark.

248 beneficial effects on memory: Kirk I. Erickson et al., “Exercise Training Increases Size of Hippocampus and Improves Memory,” PNAS 108, no. 7 (2011): 3017–22.

248 waiting for neuroplasticity: Chittaranjan Andrade and N. Sanjay Kumar Rao, “How Antidepressant Drugs Act: A Primer on Neuroplasticity as the Eventual Mediator of Antidepressant Efficacy,” Indian Journal of Psychiatry 52, no. 4 (2010): 378.

248 elevated levels of the growth factor BDNF: Biao Chen et al., “Increased Hippocampal BDNF Immunoreactivity in Subjects Treated with Antidepressant Medication,” Biological Psychiatry 50, no. 4 (2001): 260–65.

248 new neuronal connections: Carrol D’Sa and Ronald S. Duman, “Antidepressants and Neuroplasticity,” Bipolar Disorders 4, no. 3 (2002): 183–94.

248 BDNF itself may well act: Heath D. Schmidt and Ronald S. Duman, “Peripheral BDNF Produces Antidepressant-Like Effects in Cellular and Behavioral Models,” Neuropsychopharmacology 35, no. 12 (2010): 2378–2391.

248 combine exercise with antidepressants: Amelia Russo-Neustadt et al., “Physical Activity–Antidepressant Treatment Combination: Impact on Brain-Derived Neurotrophic Factor and Behavior in an Animal Model,” Behavioral Brain Research 120, no. 1 (2001): 87–95.

248 chronic stress not only tanks your mood: Christopher Pittenger and Ronald S. Duman, “Stress, Depression, and Neuroplasticity: A Convergence of Mechanisms,” Neuropsychopharmacology 33, no. 1 (2007): 88–109.

248 endocannabinoid system is a major influencer: Gregory L. Gerdeman and David M. Lovinger, “Emerging Roles for Endocannabinoids in Long-Term Synaptic Plasticity,” British Journal of Pharmacology 140, no. 5 (2003): 781–89.

248 synapses connect: If the breakdown of the endocannabinoid 2-AG (2-arachidonoylglycerol) is blocked, you see more hippocampal neuroplasticity as well as antidepressant and antianxiety effects.

248 Fat cells release cytokines: R. C. Shelton and A. H. Miller, “Eating Ourselves to Death (and Despair): The Contribution of Adiposity and Inflammation to Depression,” Progress in Neurobiology 91 (2010): 275–99.

248 fatter patients have a lamer response: N. Oskooilar et al., “Body Mass Index and Response to Antidepressants in Depressed Research Subjects,” Journal of Clinical Psychiatry 70 (2009): 1609–10.

248 Obese individuals have the bad combo: Gregory F. Oxenkrug, “Metabolic Syndrome, Age-Associated Neuroendocrine Disorders, and Dysregulation of Tryptophan—Kynureninee Metabolism,” Annals of the New York Academy of Sciences 1199, no. 1 (2010): 1–14.

248 When the weight is taken off: L. Breum et al., “Twenty-Four-Hour Plasma Tryptophan Concentrations and Ratios Are Below Normal in Obese Subjects and Are Not Normalized by Substantial Weight Reduction,” American Journal of Clinical Nutrition 77 (2003): 1112–18; G. Brandacher et al., “Bariatric Surgery Cannot Prevent Tryptophan Depletion Due to Chronic Immune Activation in Morbidly Obese Patients,” Obesity Surgery 16 (2006): 541–48.

248 Being obese (abdominal fat in particular): F. S. Luppino et al., “Overweight, Obesity, and Depression: A Systematic Review and Meta-analysis of Longitudinal Studies,” Archives of General Psychiatry 67 (2010): 220–29; Kristy Sanderson et al., “Overweight and Obesity in Childhood and Risk of Mental Disorder: A 20-Year Cohort Study,” Australian and New Zealand Journal of Psychiatry 45, no. 5 (2011): 384–92.

248 anxiety disorders: G. Gariepy et al., “The Association Between Obesity and Anxiety Disorders in the ­Population: A Systematic Review and Meta-analysis,” International Journal of Obesity 34, no. 3 (2010): 407–19.

248–349 panic attacks, generalized anxiety: Nancy M. Petry et al., “Overweight and Obesity Are Associated with Psychiatric Disorders: Results from the National Epidemiologic Survey on Alcohol and Related Conditions,” Psychosomatic Medicine 70, no. 3 (2008): 288–97.

249 People with severe depression: Arianne K. B. van Reedt Dortland et al., “Longitudinal Relationship of Depressive and Anxiety Symptoms with Dyslipidemia and Abdominal Obesity,” Psychosomatic Medicine 75, no. 1 (2013): 83–89.

249 Obese laboratory animals: Gordon Winocur et al., “Memory Impairment in Obese Zucker Rats: An Investigation of Cognitive Function in an Animal Model of Insulin Resistance and Obesity,” Behavioral Neuroscience 119, no. 5 (2005): 1389; Susan A. Farr et al., “Obesity and Hypertriglyceridemia Produce Cognitive Impairment,” Endocrinology 149, no. 5 (2008): 2628–36.

249 Fat cells create a proinflammatory cytokine: Joanna R. Erion et al., “Obesity Elicits Interleukin 1-Mediated Deficits in Hippocampal Synaptic Plasticity,” Journal of Neuroscience 34, no. 7 (2014): 2618–31.

250 seven-minute workouts: See 7-min.com.

250 brain is much less likely to go into panic mode: Jack M. Gorman et al., “Ventilatory Physiology of ­Patients with Panic Disorder,” Archives of General Psychiatry 45, no. 1 (1988): 31.

251 a transient hypofrontality: Arne Dietrich, “Transient Hypofrontality as a Mechanism for the Psychological Effects of Exercise,” Psychiatry Research 145, no. 1 (2006): 79–83.

251 activates the endocannabinoid system: P. B. Sparling et al., “Exercise Activates the Endocannabinoid System,” Neuroreport 14 (2003): 2209–11; A. Dietrich and W. F. McDaniel, “Cannabinoids and Exercise,” British Journal of Sports Medicine 38 (2004): 50–57; David A. Raichlen et al., “Exercise-Induced Endocannabinoid Signaling Is Modulated by Intensity,” European Journal of Applied Physiology 113, no. 4 (2013): 869–75.

251 rewarding effects both during and after exercise: David A. Raichlen et al., “Wired to Run: Exercise-Induced Endocannabinoid Signaling in Humans and Cursorial Mammals with Implications for the “Runner’s High,” Journal of Experimental Biology 215, no. 8 (2012): 1331–36.

251 In lab rats, even a single session: Giovane Galdino et al., “Acute Resistance Exercise Induces Antinociception by Activation of the Endocannabinoid System in Rats,” Anesthesia and Analgesia (2014).

251 Myofascial manipulation: John M. McPartland, “Expression of the Endocannabinoid System in Fibroblasts and Myofascial Tissues,” Journal of Bodywork and Movement Therapies 12, no. 2 (2008): 169–82.

252 positive effects of exercise on memory: Matthew N. Hill et al., “Endogenous Cannabinoid Signaling Is Required for Voluntary Exercise-Induced Enhancement of Progenitor Cell Proliferation in the Hippocampus,” Hippocampus 20, no. 4 (2010): 513–23.

252 exercise-induced memory formation improves: Talita H. Ferreira-Vieira et al., “A Role for the Endocannabinoid System In Exercise-Induced Spatial Memory Enhancement in Mice,” Hippocampus 24, no. 1 (2014): 79–88.

252 Mice allowed to run obsessively: Timothy J. Schoenfeld et al., “Physical Exercise Prevents Stress-Induced Activation of Granule Neurons and Enhances Local Inhibitory Mechanisms in the Dentate Gyrus,” Journal of Neuroscience 33, no. 18 (2013): 7770–77.

252 helps to lower high blood pressure: Rod K. Dishman et al., “Neurobiology of Exercise,” Obesity 14, no. 3 (2006): 345–56.

252 Motor skills training and exercise: Ibid.

253 Inactivity physically shrinks your brain: Ratey with Hagerman, Spark.

253 massively increases neurogenesis: Andrea K. Olson et al., “Environmental Enrichment and Voluntary Exercise Massively Increase Neurogenesis in the Adult Hippocampus Via Dissociable Pathways,” Hippocampus 16, no. 3 (2006): 250–60.

253 “apt to zap . . . the nervous system”: Nicholas A. Mischel et al., “Physical (in) Activity-Dependent Structural Plasticity in Bulbospinal Catecholaminergic Neurons of Rat Rostral Ventrolateral Medulla,” Journal of Comparative Neurology 522, no. 3 (2014): 499–513.

253 BDNF helps to promote serotonin neuron growth: Keri Martinowich and Bai Lu, “Interaction Between BDNF and Serotonin: Role in Mood Disorders,” Neuropsychopharmacology 33, no. 1 (2007): 73–83.

253 exercise creates a cascade of neurotransmitters: Ratey with Hagerman, Spark.

253 One author likens going for a run: Ibid.

253 Exercise has anti-inflammatory properties: Anne Marie W. Petersen and Bente Klarlund Pedersen, “The Anti-inflammatory Effect of Exercise,” Journal of Applied Physiology 98, no. 4 (2005): 1154–62.

253 cytokines from skeletal: Called myokines.

253 proinflammatory cytokines: Called adipokines.

253 Decrease inflammation and you lower your risk: Michael Gleeson et al., “The Anti-inflammatory Effects of Exercise: Mechanisms and Implications for the Prevention and Treatment of Disease,” Nature Reviews Immunology 11, no. 9 (2011): 607–15.

254 those with higher inflammatory markers: C. D. Rethorst et al., “Pro-inflammatory Cytokines as ­Predictors of Antidepressant Effects of Exercise in Major Depressive Disorder,” Molecular Psychiatry 18 (2013): 1119.

254 Mice fed a high-fat diet: Pontus Boström et al., “A PGC1-[Agr]-Dependent Myokine That Drives Brown-Fat-like Development of White Fat and Thermogenesis,” Nature 481, no. 7382 (2012):

463–68.

255 it feels easier if their “voices” tell them: Anthony W. Blanchfield et al., “Talking Yourself Out of Exhaustion: The Effects of Self-Talk on Endurance Performance,” Medicine and Science in Sports and Exercise 46, no. 5 (2014): 998-1007.

255 Use your smartphone: Abby C. King et al., “Promoting Physical Activity Through Handheld Computer Technology,” American Journal of Preventive Medicine 34, no. 2 (2008): 138–42.

255 “I say that inner beauty”: Osmel Sousa, New York Times quote of the day, November 7, 2003.

255 girls learn . . . they will be judged on their looks: Joan Jacobs Brumberg, The Body Project: An Intimate History of American Girls (New York: Random House, 1998); Joan Jacobs Brumberg, Fasting Girls: The Emergence of Anorexia Nervosa as a Modern Disease (Cambridge, MA: Harvard University Press 1998).

255 “For women . . . eyes of others”: Germaine Greer, The Female Eunuch (London: MacGibbon and Kee, 1970), 28.

256 Plucked eyebrows, collagen-enhanced lips: Mitchel P. Goldman and Arnost Fronek, “Anatomy and Pathophysiology of Varicose Veins,” Journal of Dermatologic Surgery and Oncology 15, no. 2 (1989): 138–46; Grant L. Peters et al., “The Effect of Crossing Legs on Blood Pressure: A Randomized Single-Blind Cross-Over Study,” Blood Pressure Monitoring 4, no. 2 (1999): 97–102.

256 Women need at least 17 percent body: Rose E. Frisch, “Fatness, Menarche, and Female Fertility,” Perspectives in Biology and Medicine 28, no. 4 (1985) 611-33.

256 Mannequins have become thinner: Minna Rintala and Pertti Mustajoki, “Could Mannequins Menstruate?” British Medical Journal 305, no. 6868 (1992): 1575.

256 as have Playboy centerfolds: Martin Voracek and Maryanne L. Fisher, “Shapely Centerfolds? Temporal Change in Body Measures: Trend Analysis,” British Medical Journal 325, no. 7378 (2002): 1447.

256 Barbie, the doll many of us: Kevin I. Norton et al., “Ken and Barbie at Life Size,” Sex Roles 34, no. 3–4 (1996): 287–94.

256 Our consumer culture: Williams, Breasts.

256 More than half of women surveyed in Glamour magazine: Laura Fraser, “Body Love, Body Hate” Glamour 201, October 1998.

257 Women who don’t feel good: Jacobs, The Body Project.

257 Girls who look at fashion magazines: Eric Stice et al., “Exposure to Media-Portrayed Thin-Ideal Images Adversely Affects Vulnerable Girls: A Longitudinal Experiment,” Journal of Social and Clinical Psychology 20, no. 3 (2001): 270–88.

257 literature linking the “thin-ideal”: M. P. Levine and L. Smolak, “Media a Context for the Development of Disordered Eating,” in The Developmental Psychopathology of Eating Disorders, L. Smolak, M. P. Levine, and R. Striegel-Moore, eds., (Mahwah, NJ: Erlbaum, 1996), 183–204; R. H. Striegel-Moore et al., “Toward an Understanding of Risk Factors for Bulimia,” American Psychologist 41 (1986): 246–63; J. K. Thompson et al., Exacting Beauty: Theory, Assessment, and Treatment of Body Image Disturbance (Washington, DC: American Psychological Association, 1999).

257 “seduction of inadequacy”: Lupita Nyong’o, Essence speech, February 27, 2014, http://www

.essence.com/2014/02/27/lupita-nyongo-delivers-moving-black-women-hollywood-acceptance

-speech/.

258 men are hardwired to respond to a woman’s: S. M. Platek and D. Singh, “Optimal Waist-to-Hip Ratios in Women Activate Neural Reward Centers in Men,” PLoS One 5, no. 2 (2010): e9042.

258 waist-hip ratio: Maryanne L. Fisher and Martin Voracek, “The Shape of Beauty: Determinants of Female Physical Attractiveness,” Journal of Cosmetic Dermatology 5, no. 2 (2006): 190–94.

258 perception of attractiveness: Many researchers have arrived at the number 0.7 as the ideal, and universally most ­attractive, ratio.

258 “reliable and honest indicator”: Devendra Singh, “Body Shape and Women’s Attractiveness: The Critical Role of Waist-to-Hip Ratio,” Human Nature 4, no. 3 (1993): 297–21.

259 more variability of women’s breasts: Williams, Breasts.

259 one breast is usually one-fifth of a cup size: Z. Hussain et al., “Estimation of Breast Volume and Its Variation During the Menstrual Cycle Using MRI and Stereology,” (2014).

259 Many men are aroused by darker areolas: Barnaby J. Dixson et al., “Eye Tracking of Men’s Preferences for ­Female Breast Size and Areola Pigmentation,” Archives of Sexual Behavior 40, no. 1 (2011a): 51–58.

260 the mammary gland needs: Williams, Breasts.

260 Breast implants will often make it: S. Bondurant et al., “Safety of Silicone Breast Implants: Report of the Committee on the Safety of Silicone Breast Implants (Washington, DC: Institute Of Medicine, 1999).

260 More than 80 percent of women surveyed: Roy Levin and Cindy Meston, “Nipple/Breast Stimulation and Sexual Arousal in Young Men and Women,” Journal of Sexual Medicine 3, no. 3 (2006): 450–54.

260 Women with ruptured implants: Williams, Breasts; S. Brown et al., “An Association of Silicone-Gel Breast Implant Rupture and Fibromyalgia,” Current Rheumatology Reports 4, no. 4 (2002): 293–98.

260 “doorknob effect”: Neal Handel et al., “A Long-Term Study of Outcomes, Complications, and Patient Satisfaction with Breast Implants,” Plastic and Reconstructive Surgery 117, no. 3 (2006): 757–67.

260 rare cancer can grow: FDA, 2013, http://www.fda.gov/medicaldevices/productsandmedicalprocedures/implantsandprosthetics/breastimplants/ucm239995.htm.

260 implants can make it harder for mammograms: Harry Hayes Jr. et al., “Mammography and Breast Implants,” Plastic and Reconstructive Surgery 82, no. 1 (1988): 1–6.

261 In the women studied who didn’t wear bras: Shaunacy Ferro, “Brassiere Support Is a Lie, Say French Scientists,” Popular Science, April 11, 2013.

261 Wearing a bra 24/7: Sydney Singer and Soma Grismaijer, Dressed to Kill: The Link Between Breast Cancer and Bras (New York: Avery Publishing Group, 1995); Sydney Singer and Soma Grismaijer, Get It Off! Understanding the Causes of Breast Pain, Cysts, and Cancer (ISCD Press, 2000).

261 Premenopausal women who don’t wear bras: C-C. Hsieh and D. Trichopoulos, “Breast Size, Handedness and Breast Cancer Risk,” European Journal of Cancer and Clinical Oncology 27, no. 2 (1991): 131–35.

261 Sleeping without a bra: A. Q. Zhang et al., “Risk Factors of Breast Cancer in Women in Guangdong and the Countermeasures,” Journal of Southern Medical University 29, no. 7 (2009): 1451–53.

261 bisphenol-A (BPA), an artificial estrogen: A. G. Recchia et al., “Xenoestrogens and the Induction of Proliferative Effects in Breast Cancer Cells Via Direct Activation of Estrogen Receptor A,” Food Additives and Contaminants 21, no. 2 (2004): 134–44.

261 BPA basically turns on and off the genes: Sandra Viviana Fernandez and Jose Russo, “Estrogen and ­Xenoestrogens in Breast Cancer,” Toxicologic Pathology 38, no. 1 (2010): 110–22.

261 When young rats are fed BPA: Leo F. Doherty et al., “In Utero Exposure to Diethylstilbestrol (DES) or Bisphenol-A (BPA) Increases EZH2 Expression in the Mammary Gland: An Epigenetic Mechanism Linking Endocrine Disruptors to Breast Cancer,” Hormones and Cancer 1, no. 3 (2010): 146–55.

262 When developing mice are exposed to atrazine: Jennifer L. Rayner et al., “Adverse Effects of Prenatal Exposure to Atrazine During a Critical Period of Mammary Gland Growth,” Toxicological Sciences 87, no. 1 (2005): 255–66.

262 at least two hundred chemicals: Ruthann A. Rudel et al., “Chemicals Causing Mammary Gland Tumors in Animals Signal New Directions for Epidemiology, Chemicals Testing, and Risk Assessment for Breast Cancer Prevention,” Cancer 109, no. S12 (2007): 2635–66.

262 when our government tests chemicals . . . they leave out looking at breasts: Williams, Breasts.

263 laser surgery lawsuits: H. Ray Jalian et al., “Increased Risk of Litigation Associated with Laser Surgery by Nonphysician Operators,” JAMA Dermatology 150, no. 4 (2014): 407–11.

263 Shaving and waxing: Claire Dendle et al., “Severe Complications of a ‘Brazilian” Bikini Wax,’ Clinical Infectious Diseases 45, no. 3 (2007): e29–e31; Allyssa L. Harris and Heidi Collins Fantasia, “Community-Associated MRSA Infections in Women,” Journal for Nurse Practitioners 6, no. 6 (2010): 435–41.

264 vulnerability to the viruses molluscum contagiosum: François Desruelles et al., “Pubic Hair Removal: A Risk Factor for ‘Minor’ STI Such as Molluscum Contagiosum?” Sexually Transmitted Infections 89, no. 3 (2013): 216.

264 herpes: Charlotte Castronovo et al., “Viral Infections of the Pubis,” International Journal of STD & AIDS 23, no. 1 (2012): 48–50.

264 contaminated wax or strips of cloth: Dendle et al., “Severe Complications of a ‘Brazilian’ Bikini Wax,” e29–e31.

264 How someone smells affects us: Karl Grammer et al., “Human Pheromones and Sexual Attraction,” European Journal of Obstetrics & Gynecology and Reproductive Biology 118, no. 2 (2005): 135–42.

264 demand for plastic surgery (called vulvoplasty) in this area: Lih Mei Liao and Sarah M. Creighton, “Requests for Cosmetic Genitoplasty: How Should Healthcare Providers Respond?” British Medical Journal 334, no. 7603 (2007): 1090–92.

264 alter your inner labia: V. Braun and C. Kitzinger, “The Perfectible Vagina: Size Matters,” Culture Health Sexuality 3 (2001): 263–77; R. Bramwell et al., “Expectations and Experience of Labial Reduction: A Qualitative Study,” BJOG 114, no. 12 (2007): 1493–99.

Chapter Twelve: You. Need. Downtime.

268 people prefer to give themselves an electric shock: Timothy D. Wilson et al., “Just Think: The Challenges of the Disengaged Mind,” Science 345, no. 6192 (2014): 75–77.

269 When we are fully present in nature: Richard Louv, The Nature Principle: Human Restoration and the End of Nature-Deficit Disorder (New York: Algonquin Books, 2012).

269 A nature walk can lead to: Rodney H. Matsuoka, “Student Performance and High School Landscapes: Examining the Links.” Landscape and Urban Planning 97, no. 4 (2010): 273–82.

269 restoring attention and decreasing mental fatigue: S. Kaplan, “The Restorative Benefits of Nature: Toward an Integrative Framework,” Journal of Environmental Psychology 15 (1995): 169–82; S. Kaplan, “Meditation, Restoration, and the Management of Mental Fatigue,” Environment and Behavior 33 (2001): 480–506.

269 Directed-attention fatigue: Rachel Kaplan and Stephen Kaplan, The Experience of Nature: A Psychological Perspective (Cambridge, Eng.: Cambridge University Press, 1989).

269 When kids with ADHD played outside: A. F. Taylor et al., “Coping with ADD: The Surprising Connection to Green Play Settings,” Environment and Behavior 33 (2001): 54–77.

270 significantly better concentration: Andrea Faber Taylor and Frances E. Kuo, “Children with Attention Deficits Concentrate Better After Walk in the Park,” Journal of Attention Disorders 12, no. 5 (2009): 402–9.

270 outdoor immersion program: Kaplan and Kaplan, The Experience of Nature.

270 reduction in anxiety: Alan Ewert, “Reduction of Trait Anxiety Through Participation in Outward Bound,” Leisure Sciences 10, no. 2 (1988): 107–17.

270 helplessness: Richard S. Newman, “Alleviating Learned Helplessness in a Wilderness Setting: An Application of Attribution Theory to Outward Bound,” in Leslie J. Fyans and American Educational Research Association, Achievement Motivation (U.S.: Springer, 1980), 312–45.

270 improved cognitive reasoning: Ruth Ann Atchley et al., “Creativity in the Wild: Improving Creative Reasoning Through Immersion in Natural Settings,” PloS One 7, no. 12 (2012): e51474.

270 Being outside in nature: Melanie Rudd et al., “Awe Expands People’s Perception of Time, Alters Decision Making, and Enhances Well-Being,” Psychological Science 23, no. 10 (2012): 1130–36.

270 three-quarters of us are deficient: Jordan Lite, “Vitamin D Deficiency Soars in the U.S.,” Scientific American, March 23, 2009.

270 twenty minutes of sunshine: That’s if you’re light skinned; if you’re dark skinned, you may need ten times this amount.

270 Low vitamin D levels: Michael Berk et al., “Vitamin D Deficiency May Play a Role in Depression,” Medical Hypotheses 69, no. 6 (2007): 1316–19; Robert H. Howland, “Vitamin D and Depression,” J Psychosoc Nurs Ment Health Serv 49, no. 2 (2011): 15–18.

270 giving patients adequate doses of vitamin D: F. M. Gloth III et al., “Vitamin D Vs. Broad Spectrum Phototherapy in the Treatment of Seasonal Affective Disorder,” Journal of Nutrition, Health & Aging 3, no. 1 (1999): 5; R. Jorde et al., “Effects of Vitamin D Supplementation on Symptoms of Depression in Overweight and Obese Subjects: Randomized Double Blind Trial,” Journal of Internal Medicine 264, no. 6 (2008): 599–609; Jason Hawrelak and Stephen P. Myers, “Vitamin D for Depression,” Journal of Complementary Medicine 8, no. 2 (2009): 62

270 One study of people in an ER: G. A. Plotnikoff and J. M. Quigley, “Prevalence of Severe Hypovitaminosis D in Patients with Persistent, Nonspecific Musculoskeletal Pain,” Mayo Clinic Proceedings 78 (2003): 1463–70.

271 fashionable sunglasses: Most opthalmologists recommend wearing sunglasses at all times to protect against UV exposure, especially if you have light-colored eyes.

271 the sunlight needs to hit your retinas: S. N. Young, “How to Increase Serotonin in the Human Brain Without Drugs,” Journal of Psychiatry and Neuroscience 32 (2007): 394–99; Mahmut Alpayci et al., “Sunglasses May Play a Role in Depression,” Journal of Mood Disorders 2, no. 2 (2012).

272 Phototherapy lamps: lighttherapyproducts.com.

272 Depression is aggravated in lab animals: Hiroyuki Mizoguchi et al., “Lowering Barometric Pressure Aggravates Depression-like Behavior in Rats,” Behavioral Brain Research 218, no. 1 (2011): 190–93.

272 A survey of thousands of suicides: Laura Hiltunen et al., “Atmospheric Pressure and Suicide Attempts in Helsinki, Finland,” International Journal of Biometeorology 56, no. 6 (2012): 1045–53.

272 temperature and humidity: See Michael Persinger, The Weather Matrix and Human Behavior (New York: Praeger, 1980).

273 Studies using negative ion generators: N. Goel et al., “Controlled Trial of Bright Light and Negative Air Ions for Chronic Depression,” Psychological Medicine 35, no. 7 (July 2005): 945–55; N. Goel and G. R. Etwaroo, “Bright Light, Negative Air Ions and Auditory Stimuli Produce Rapid Mood Changes in a Student Population: A Placebo-Controlled Study,” Psychological Medicine 36, no. 9 (September 2006): 1253–63.

273 lower stress and inflammatory markers: H. Nakane et al., “Effect of Negative Air Ions on Computer Operation, Anxiety and Salivary Chromogranin A-Like Immunoreactivity,” International Journal of Psychophysiology 46, no. 1 (October 2002): 85–89.

273 increase alertness and mental energy: Pierce J. Howard, The Owner’s Manual for the Brain: Everyday Applications from Mind-Brain Research (Austin, TX: Bard Press, 2000).

273 ability to cope with stress and recover: Roger S. Ulrich et al., “Stress Recovery During Exposure to Natural and Urban Environments,” Journal of Environmental Psychology 11, no. 3 (1991): 201–30.

273 Green exercise boosts resilience: Q. Li et al., “Forest Bathing Enhances Human Natural Killer Activity and Expression of Anti-Cancer Proteins,” International Journal of Immunopathology and Pharmacology 20, no. 2 Suppl. (2007): 3.

273 city folks also have greater anterior cingulate activity: F. Lederbogen et al., “City Living and Urban Upbringing Affect Neural Social Stress Processing in Humans,” Nature 474 (June 2011): 498.

273 anterior cingulate . . . implicated in depressive symptoms: C. G. Davey et al., “Regionally Specific Alterations in Functional Connectivity of the Anterior Cingulate Cortex in Major Depressive Disorder,” Psychological Medicine 42, no. 10 (2012): 2071–81.

273 more positive outlook on life: Kaplan and Kaplan, The Experience of Nature.

273 genuinely happy people recover from illness: Louv, The Nature Principle.

273 22 percent of people felt more depressed: Ecotherapy: The Green Agenda for Mental Health. Executive Summary, Mind, 2007. http://www.mind.org.uk/media/211252/Ecotherapy_The_green_agenda_for_mental_health_Executive_summary.pdf.

273 The medical mile: Louv, The Nature Principle, 85.

274 Patients who have a view of a tree: Roger S. Ulrich, “View Through a Window May Influence Recovery from Surgery,” Science 224, no. 4647 (1984): 420–21.

274 Canadian studies report that children: James Raffan, “Nature Nurtures: Investigating the Potential of School Grounds,” http://www.evergreen.ca/docs/res/Nature-Nurtures.pdf.

274 people in indoor workspaces with a window: Peter H. Kahn Jr. et al., “A Plasma Display Window?—The Shifting Baseline Problem in a Technologically Mediated Natural World,” Journal of Environmental Psychology 28, no. 2 (2008): 192–99.

274 The research of Frances Kuo shows that: Frances E. Kuo and William C. Sullivan, “Environment and Crime in the Inner City Does Vegetation Reduce Crime?” Environment and Behavior 33, no. 3 (2001a): 343–67.

274 Chicago public-housing projects: Frances E. Kuo and William C. Sullivan, “Aggression and Violence in the Inner City Effects of Environment Via Mental Fatigue,” Environment and Behavior 33, no. 4 (2001): 543–71.

274 Couples in which both partners use cannabis: Phillip H. Smith et al., “Couples’ Marijuana Use Is Inversely Related to Their Intimate Partner Violence Over the First 9 Years of Marriage,” Psychology of Addictive Behaviors 28, no. 3 (2014): 734.

274 makes us more caring and generous: Netta Weinstein et al., “Can Nature Make Us More Caring? Effects of Immersion in Nature on Intrinsic Aspirations and Generosity,” Personality and Social Psychology Bulletin 35, no. 10 (2009): 1315–29.

275 hunter-gatherers . . . egalitarian and communal: Elizabeth A. Cashdan, “Egalitarianism Among Hunters and Gatherers,” American Anthropologist 82, no. 1 (1980): 116–20.

275 Antibacterial soaps and overprescribed antibiotics create “superbugs”: H. Okada et al., “The ‘Hygiene Hypothesis’ for Autoimmune and Allergic Diseases: An Update,” Clinical & Experimental Immunology 160, no. 1 (2010): 1–9; Graham A. W. Rook, “Hygiene Hypothesis and Autoimmune Diseases,” Clinical Reviews in Allergy & Immunology 42, no. 1 (2012): 5–15.

275 Babies born by a Caesarean section: Michael Pollan, “Some of My Best Friends Are Germs,” New York Times Magazine, May 15, 2013; Josef Neu and Jona Rushing, “Cesarean Versus Vaginal Delivery: Long-Term Infant Outcomes and the Hygiene Hypothesis,” Clinics in Perinatology 38, no. 2 (2011): 321.

276 children born by C-section are more likely: J. Blustein et al., “Association of Cesarean Delivery with Child Adiposity from Age 6 Weeks to 15 Years,” International Journal of Obesity 37, no. 7 (2013): 900–6.

276 combine high-calorie foods with antibiotics in mice: L. Cox et al., “Altering the Intestinal Microbiota During a Critical Developmental Window Has Lasting Metabolic Consequences,” Cell 158, no. 4 (2014): 705–21.

276 triclosan and triclocarban . . . disrupting thyroid function: K. M. Crofton et al., “Short-Term in Vivo Exposure to the Water Contaminant Triclosan: Evidence for Disruption of Thyroxine,” Environmental Toxicology and Pharmacology 24 (2007): 194–97.

276 amplifying hormone levels: R. H. Gee et al., “Oestrogenic and Androgenic Activity of Triclosan in Breast Cancer Cells,” Journal of Applied Toxicology 28 (2008): 78–91.

276 promoting drug-resistant infections: M. Braoudaki and A. C. Hilton, “Low Level of Cross-Resistance Between Triclosan and Antibiotics in Escherichia Coli K-12 and E. Coli O55 Compared to E. Coli O157,” FEMS Microbiology Letters 235 (2004): 305–9.

276 antibacterial chemicals are found in our urine: A. M. Calafat et al., “Urinary Concentrations of Triclosan in the U.S. Population: 2003–2004,” Environmental Health Perspectives 116, no. 3 (2008): 303–7.

276 our breast milk: M. Allmyr et al., “Triclosan in Plasma and Milk from Swedish Nursing Mothers and Their Exposure Via Personal Care Products,” Science of the Total Environment 372, no. 1 (2006): 87–93.

276 Mice given live M. vaccae: Christopher A. Lowry et al., “Identification of an Immune-Responsive Mesolimbocortical Serotonergic System: Potential Role in Regulation of Emotional Behavior,” Neuroscience 146, no. 2 (2007): 756–72.

276 regulating the stress response: T. G. Dinan and J. F. Cryan, “Regulation of the Stress Response by the Gut Microbiota: Implications for Psychoneuroendocrinology,” Psychoneuroendocrinology 37 (2012): 1369–78.

276 administering Lactobacillus helveticus: M. Messaoudi et al., “Assessment of Psychotropic-like Properties of a Probiotic Formulation (Lactobacillus Helveticus R0052 and Bifidobacterium Longum R0175) in Rats and Human Subjects,” British Journal of Nutrition 105 (2011): 755–64.

276 certain bacteria are essential for normal social development: L. Desbonnet et al., “Microbiota is ­Essential for Social Development in the Mouse,” Molecular Psychiatry 19, no. 2 (2014): 146.

276 autistic-like behavior improves: Elaine Y. Hsiao et al., “Microbiota Modulate Behavioral and Physiological Abnormalities Associated with Neurodevelopmental Disorders,” Cell 155, no. 7 (2013): 1451–63.

277 “Minimize unnecessary antibiotics . . . in the dirt and with animals”: Pollan, “Some of My Best Friends Are Germs.”

277 higher levels of hormones in their urine: Thomas Heberer, “Tracking Persistent Pharmaceutical Residues from Municipal Sewage to Drinking Water,” Journal of Hydrology 266, no. 3 (2002): 175–89.

277 Hormones in the drinking water: David Margel and Neil E. Fleshner, “Oral Contraceptive Use Is Associated with Prostate Cancer: An Ecological Study,” British Medical Journal Open 1, no. 2 (2011).

277 women’s risk of breast cancer: Mark Clemons and Paúl Goss, “Estrogen and the Risk of Breast Cancer,” New England Journal of Medicine 344, no. 4 (2001): 276–85.

277 When plastics are heated in a microwave: Mariah Blake, “The Scary New Evidence on BPA-Free Plastics and the Big Tobacco–Style Campaign to Bury It,” Mother Jones, March/April 2014.

277 chronic exposure brings on puberty: Kembra L. Howdeshell et al., “Environmental Toxins: Exposure to Bisphenol A Advances Puberty,” Nature 401, no. 6755 (1999): 763–64.

278 asthma, heart and liver ailments, ADHD, and cancer: Blake, “The Scary New Evidence on BPA-Free Plastics.”

278 switch off genes that suppress tumor growth: Ana M. Soto and Carlos Sonnenschein, “Environmental Causes of Cancer: Endocrine Disruptors as Carcinogens,” Nature Reviews Endocrinology 6, no. 7 (2010): 363–70.

278 “A poison kills you”: Blake, “The Scary New Evidence on BPA-Free Plastics.”

278 No industry-funded studies have reported significant effects: Saal Vom et al., “An Extensive New Literature Concerning Low-Dose Effects of Bisphenol A Shows the Need for a New Risk Assessment,” Environmental Health Perspectives 113, no. 8 (2005): 926.

278 it’s been replaced by other chemicals: Chun Z. Yang et al., “Most Plastic Products Release Estrogenic Chemicals: A Potential Health Problem That Can Be Solved,” Environmental Health Perspectives 119, no. 7 (2011): 989.

278 The billion-dollar plastics industry: Blake, “The Scary New Evidence on BPA-Free Plastics.”

278 Phthalates. . . correlated with cancers and birth defects: Evanthia Diamanti-Kandarakis et al., “Endocrine-Disrupting Chemicals: An Endocrine Society Scientific Statement,” Endocrine Reviews 30, no. 4 (2009): 293–42.

278 decreased sperm quality: Elisabeth Carlsen et al., “Evidence for Decreasing Quality of Semen During Past 50 Years,” British Medical Journal 305, no. 6854 (1992): 609.

278 abnormal testes development: N. E. Skakkebaek et al., “Association Between Testicular Dysgenesis Syndrome (TDS) and Testicular Neoplasia: Evidence from 20 Adult Patients with Signs of Maldevelopment of the Testis,” APMIS 111, no. 1 (2003): 1–9.

278 interfere with testosterone production: Juliane-Susanne Schmidt et al., “Effects of Di (2-Ethylhexyl) Phthalate (DEHP) on Female Fertility and Adipogenesis in C3H/N Mice,” Environmental Health Perspectives 120, no. 8 (2012): 1123.

278 lower fertility: Germaine M. Buck Louis et al., “Urinary Bisphenol A, Phthalates, and Couple Fecundity: The Longitudinal Investigation of Fertility and the Environment (LIFE) Study,” Fertility And Sterility (2014).

278 reproductive toxins: Vanessa R. Kay et al., “Reproductive and Developmental Effects of Phthalate Diesters in Females,” Critical Reviews in Toxicology 43, no. 3 (2013): 200–19.

278 brings on puberty earlier: Jonathan R. Roy et al., “Estrogen-like Endocrine Disrupting Chemicals Affecting Puberty in Humans—a Review,” Medical Science Monitor: International Medical Journal of Experimental and Clinical Research 15, no. 6 (2009): RA137–45; Jefferson P. Lomenick et al., “Phthalate Exposure and Precocious Puberty in Females,” Journal of Pediatrics 156, no. 2 (2010): 221–25.

278 linked with breast cancer: P. D. Darbre, “Environmental Oestrogens, Cosmetics and Breast Cancer,” Best Practice & Research Clinical Endocrinology & Metabolism 20, no. 1 (2006): 121–43; Sandra Viviana Fernandez and Jose Russo, “Estrogen and Xenoestrogens in Breast Cancer,” Toxicologic Pathology 38, no. 1 (2010): 110–22.

278 diabetes, and obesity: Richard W. Stahlhut et al., “Concentrations of Urinary Phthalate Metabolites Are Associated with Increased Waist Circumference and Insulin Resistance in Adult U.S. Males,” Environmental Health Perspectives (2007): 876–82; P. Monica Lind et al., “Circulating Levels of Phthalate Metabolites Are Associated with Prevalent Diabetes in the Elderly,” Diabetes Care 35, no. 7 (2012): 1519–24; Tamarra James-Todd et al., “Urinary Phthalate Metabolite Concentrations and Diabetes Among Women in the National Health and Nutrition Examination Survey (NHANES) 2001–2008,” Environmental Health Perspectives 120, no. 9 (2012): 1307.

279 indigenous cultures, nature is where the spirit is: Ralph Metzner, “The Split Between Spirit and Nature in European Consciousness,” Trumpeter 10, no. 1 (1993), http://trumpeter.athabascau.ca/index.php/trumpet/article/viewArticle/407/658.

279 cannabis-based medicines . . . resilience to stress: R. J. Bluett et al., “Central Anandamide Deficiency Predicts Stress-Induced Anxiety: Behavioral Reversal Through Endocannabinoid Augmentation,” Translational Psychiatry 4, no. 7 (2014): e408.

279–280 Hemp and cannabis . . . fiber, fuel, and food: Holland, The Pot Book.

280 go out and find beauty in the world: O. R. W. Pergams and P. A. Zaradic, “Is Love of Nature in the U.S. Becoming Love of Electronic Media? 16-Year Downtrend in National Park Visits Explained by Watching Movies, Playing Video Games, Internet Use, and Oil Prices,” Journal of Environmental Management 80 (2006): 387–93.

280 actually disrupt our endocrine system and cause cancer: Soto and Sonnenschein, “Environmental Causes of Cancer,” 363–70.

280 We eat artificial sweeteners: Qing Yang, “Gain Weight by ‘Going Diet?’ Artificial Sweeteners and the Neurobiology of Sugar Cravings: Neuroscience 2010,” The Yale Journal of Biology and Medicine 83, no. 2 (2010): 101.

280 Men ogle plastic breasts: Donald L. Hilton Jr, “Pornography Addiction–A Supranormal Stimulus Considered in the Context of Neuroplasticity,” Socioaffective Neuroscience & Psychology 3 (2013).

280 Chemicals in plastics: Steven F. Hotze, Hormones, Health, and Happiness (Houston: Forrest Publishing, 2005); Laura E. Corio, The Change Before the Change (New York: Bantam, 2000); Tyrone N. Hayes et al., “Atrazine Induces Complete Feminization and Chemical Castration in Male African Clawed Frogs (Xenopus Laevis),” Proceedings of the National Academy of Sciences 107, no. 10 (2010): 4612–17; Vanessa R. Kay, Christina Chambers, and Warren G. Foster, “Reproductive and Developmental Effects of Phthalate Diesters in Females,” Critical Reviews in Toxicology 43, no. 3 (2013): 200–219.

281 Exposure to others’ traumas: P. Vasterman et al. “The Role of The Media and Media Hypes in the Aftermath of Disasters,” Epidemiological Review 27 (2005): 107–14; K. M. Wright et al., “The Shared Experience of Catastrophe: An Expanded Classification of the Disaster Community,” American Journal of Ortho­psychiatry 60, no. 1 (1990): 35–42; Alison E. Holman et al., “Media’s Role in Broadcasting Acute Stress Following the Boston Marathon Bombings,” Proceedings of the National Academy of Sciences 111, no. 1 (2014): 93–98.

281 America now has more Internet-connected devices: NPD Group, Connected Intelligence, Connected Home Report, press release quoted in USA Today, January 2, 2013.

281 “continuous partial attention”: Linda Stone, “Continuous Partial Attention–Not the Same as Multi-Tasking,” Businessweek 24 (2008).

281 drains our ability to focus: Louv, The Nature Principle.

281 When a research subject hears his phone ring: Martin Lindstrom, “You Love Your iPhone. Literally,” New York Times, September 30, 2011.

281 A new term, nomophobia: Manjeet Singh Bhatia, “Cell Phone Dependency—a New Diagnostic Entity,” Delhi Psychiatry Journal 11, no. 2 (2008): 123–24.

282 it is impossible to get enough of something: Maté, When the Body Says No.

282 When we’re tense or fearful: Walton T. Roth et al., “Voluntary Breath Holding in Panic and Generalized Anxiety Disorders,” Psychosomatic Medicine 60, no. 6 (1998): 671–79; Patricia Hill Bailey, “The Dyspnea-Anxiety-Dyspnea Cycle—COPD Patients’ Stories of Breathlessness: “It’s Scary/When You Can’t Breathe,” Qualitative Health Research 14, no. 6 (2004): 760–78.

285 Meditation can decrease stress: Maria B. Ospina et al., “Meditation Practices for Health,” Agency for Healthcare Research and Quality, publication no. 07–E010, 2007.

285 improve resilience: Perla Kaliman et al., “Rapid Changes in Histone Deacetylases and Inflammatory Gene Expression in Expert Meditators,” Psychoneuroendocrinology 40 (2014): 96–107.

285 tamp down inflammation: T. W. Pace et al., “Effect of Compassion Meditation on Neuroendocrine, Innate Immune and Behavioral Responses to Psychosocial Stress,” Psychoneuroendocrinology 34 (2009): 87–98; C. Reardon et al., “Lymphocyte-Derived Ach Regulates Local Innate but Not Adaptive Immunity,” PNAS 110 (2013): 1410–15.

285 benefiting genes that control energy metabolism: M. K. Bhasin et al., “Relaxation Response Induces Temporal Transcriptome Changes in Energy Metabolism, Insulin Secretion and Inflammatory Pathways,” PLoS One 8, no. 5 (2013): e62817.

285 Meditation practices are associated with neuroplastic changes: Lisa A. Kilpatrick et al., “Impact of Mindfulness-Based Stress Reduction Training on Intrinsic Brain Connectivity,” Neuroimage 56, no. 1 (2011): 290–98.

285 strengthening these connections improves self-regulation: Britta K. Hölzel et al., “How Does Mindfulness Meditation Work? Proposing Mechanisms of Action from a Conceptual and Neural Perspective,” Perspectives on Psychological Science 6, no. 6 (2011a): 537–59.

285 longer people have an established meditation practice: Eileen Luders, “The Unique Brain Anatomy of Meditation Practitioners: Alterations in Cortical Gyrification,” Frontiers in Human Neuroscience 6 (2012).

285 Meditation can help you be more resilient to stress: Richard J. Davidson and Sharon Begley, The Emotional Life of Your Brain: How Its Unique Patterns Affect the Way You Think, Feel, and Live—and How You Can Change Them (New York: Penguin, 2012).

285 “top-down” control: Dennis S. Charney, “Psychobiological Mechanisms of Resilience and Vulnerability. Implications for Successful Adaptation to Extreme Stress,” FOCUS: The Journal of Lifelong Learning in Psychiatry 2, no. 3 (2004): 368–91.

285 stronger connections between the PFC and the hippocampus: Negar Fani et al., “White Matter Integrity in Highly Traumatized Adults with and without Post-traumatic Stress Disorder,” Neuropsychopharmacology 37, no. 12 (2012): 2740–46.

286 Advanced meditators are better at inhibiting: Christopher A. Brown and Anthony K. P. Jones, “Meditation Experience Predicts Less Negative Appraisal of Pain: Electrophysiological Evidence for the Involvement of Anticipatory Neural Responses,” Pain 150, no. 3 (2010): 428–38.

286 Even after just eight weeks of mindfulness training: Britta K. Hölzel et al., “Mindfulness Practice Leads to Increases in Regional Brain Gray Matter Density,” Psychiatry Research: Neuroimaging 191, no. 1 (2011): 36–43.

286 People who meditate are not only more: Teresa M. Edenfield and Sy Atezaz Saeed, “An Update on Mindfulness Meditation as a Self-Help Treatment for Anxiety and Depression,” Psychology Research and Behavior Management 5 (2011): 131–41; R. J. Davidson et al., “Alterations in Brain and Immune Function Produced by Mindfulness Meditation,” Psychosomatic Medicine 65, no. 4 (2003): 564–70; P. Grossman et al., “Mindfulness-Based Stress Reduction and Health Benefits. A Meta-analysis,” Journal of Psychosomatic Research 57, no. 1 (2004): 35–43; Peter Sedlmeier et al., “The Psychological Effects of Meditation: A Meta-analysis,” Psychological Bulletin 138, no. 6 (2012): 1139–71.

286 Meditation: Check out mindspace.com for an app that can help you learn to meditate.

286 job is to be there: Staying “on task” will make you feel great. Instead, most of us tend to think up how to torture ourselves when we’ve nothing better to do. While we make the bed and wash dishes, we court drama and replay scenes where we were wronged or excluded instead of allowing ourselves those few moments of the pleasure of a well-made bed and hydrotherapy.

287 Having a sense of awe: Rudd et al., “Awe Expands People’s Perception of Time,” Psychological Science 23, no. 20 (2012): 1130–36.

Conclusion: Staying Sane in an Insane World

289 Too many of us are out of sync: John Bowlby, “Maternal Care and Mental Health,” Journal of Consulting Psychology 16, no. 3 (1952): 232; Maté, When the Body Says No.

289 compulsive consumers: Americans pour seven million dollars into the U.S. retail industry every minute, purchasing an average of 1,440 McDonald’s burgers, 5,695 Starbucks’ drinks, and eighty-four thousand dollars’ worth of Amazon items.

294 Women are made to be in tune: Winnifred Berg Cutler et al., “Lunar and Menstrual Phase Locking,” American Journal of Obstetrics & Gynecology 137, no. 7 (1980): 834–39; W. B. Cutler, “The Moon and Menses,” American Journal of Obstctrics & Gynecology 160, no. 2 (1989): 522–23.

Appendix: Naming Names: A Guide to Selected Drugs

321 this time by: Rosemary Bassoon et al., “Efficacy and safety of viagiain estrogedized women with sexual Dysfunction Associated with Female Sexual Aromsal Disorder,” International Journal of Gynecolosy and obstetries supp 1.5 (2002).

333 manufacturing of the drug oxycodone: Katherin Eban, “OxyContin: Purdue Pharma’s Painful Medicine” Fortune 164, no. 8 (2011): 76.

333 Emergency room visits: R. E. Cai et al., “Emergency Department Visits Involving Nonmedical Use of ­Selected Prescription Drugs in the United States, 2004–2008,” Journal of Pain and Palliative Care Pharmacotherapy 24, no. 3 (2010): 293–97.

334 until our bodies finally say no: Gabor Mate, When the Body Says No (Hoboken: Wiley, 2011).

334 women with a history of childhood sexual abuse: James Morrison, “Childhood Sexual Histories of Women,” American Journal of Psychiatry 146, no. 2 (1989): 239–41; Page Ouimette et al., “Physical and Sexual Abuse Among Women and Men with Substance Use Disorder,.” Alcoholism Treatment Quarterly 18, no. 3 (2000): 7–17.

335 prescriptions for stimulants: What Is prescription Drug Abuse? NIDA, August 7, 2012, nida

.nih.gov/researchreports/prescription/prescription?.html.

337 Cocaethylene is even more likely: W. L. Hearn, et al., “Cocaethylene Is More Potent Than Cocaine in Mediating Lethality,” Pharmacology Biochemistry and Behavior 39, no. 2 (1991): 531–33.

337 visits reporting Ecstasy use: SAMHSA, 2012, oas.samsa.gov/2kll/DAWN027/ecstasy.htm.

338 Nineteen substances were so obscure: Frank Owen and Lera Gavin, “Molly Is the New Club Drug, But What’s in It?” Playboy, Oct. 20, 2013.

338 no guarantee of purity: See ecstasydata.org for examples of pill and powder testing.

338 medically supervised settings: Michael C. Mithoefer et al.,”The Safety and Efficacy of 3-, 4-Methylenedioxymethamphetamine-Assisted Psychotherapy in Subjects with Chronic, Treatment-Resistant Posttraumatic Stress Disorder: The First Randomized Controlled Pilot Study,” Journal of Psychopharmacology 25, no. 4 (2011): 439–52.

338 recreational setting: For more information on MDMA please see the nonprofit book Ecstasy: The Complete Guide, edited by Julie Holland, M.D. (Rochester, VT: Park Street Press) 2001.

339 Eighty-two percent: Rasmussen Report “82% Say US Not Winning the War on Drugs” August 18, 2013.

339 believe cannabis should be legal: Pew Research, “Majority Now Supports Legalizing Marijuana” April 4, 2013.

340 lower their use of opiates significantly: D. I. Abrams et al.,”Cannabinoid–Opioid Interaction in Chronic Pain,” Clinical Pharmacology & Therapeutics 90, no. 6 (2011): 844–51.

340 makers of Oxycontin and Vicodin: Lee Fang et al., “The Anti-Pot Lobby’s Big Bankroll: The Opponents of Marijuana-Law Reform Insist That Legalization Is Dangerous—But the Biggest Threat Is to Their Own Bottom Line,” Nation 299, nos. 3–4 (2014): 12–18.

340 and go on to become addicted: James C. Anthony, Lynn A. Warner, and Ronald C. Kessler, “Comparative Epidemiology of Dependence on Tobacco, Alcohol, Controlled Substances, and Inhalants: Basic Findings from the National Comorbidity Survey,” Experimental and Clinical Psychopharmacology 2, no. 3 (1994): 244.

341 Sucking releases endorphins: Ester Fride et al., “Critical Role of the Endogenous Cannabinoid System in Mouse Pup Suckling and Growth,” European Journal of Pharmacology 419, no. 2 (2001): 207–14.

341 Acupuncture involving ear stimulation: Mehdi Tahiri et al., “Alternative Smoking Cessation Aids: A Meta-Analysis of Randomized Controlled Trials,” The American Journal of Medicine 125, no. 6 (2012): 576–84.

366 The hippy gynoid shape: Corio, The Change Before the Change.

366 Cortisol counteracts insulin: Claudia Gragnoli, “Depression and Type 2 Diabetes: Cortisol Pathway Implication and Investigational Needs,” Journal of Cellular Physiology 227, no. 6 (2012): 2318–22.

366 stops the production of a transporter: Soonho Kwon and Kathie L. Hermayer, “Glucocorticoid-Induced Hyperglycemia,” American Journal of the Medical Sciences 345, no. 4 (2013): 274–77; Paul E. Marik and Rinaldo Bellomo, “Stress Hyperglycemia: An Essential Survival Response,” Critical Care 17, no. 2 (2013): 305; Nyika D. Kruyt et al., “Stress-Induced Hyperglycemia in Healthy Bungee Jumpers Without Diabetes Due to Decreased Pancreatic B-Cell Function and Increased Insulin Resistance,” Diabetes Technology & Therapeutics 14, no. 4 (2012): 311–14.

367 Estrogen increases the expression: C. L. Bethea et al., “Ovarian Steroids and Serotonin Neural Function,” Molecular Neurobiology 18, no. 2 (1998): 87–123.

367 directly increases serotonin activity: I. Hindberg and O. Naesh, “Serotonin Concentrations in Plasma and Variations During the Menstrual Cycle,” Clinical Chemistry 38, no. 10 (1992):

2087–89.

367 while estrogen creates high levels: Corio, The Change Before the Change.

367 High progesterone also inhibits: Ibid.

367 Leg spasms occur in 40 percent: Corio, The Change Before the Change.

368 Two androgens: Corio, The Change Before the Change.

368 Tibolone, a medicine that raises: Susan R. Davis, “The Effects of Tibolone on Mood and Libido,” Menopause 9, no. 3 (2002): 162–70.

369 In women with higher SHBG: Barbara A. Gower and Lara Nyman, “Associations Among Oral Estrogen Use, Free Testosterone Concentration, and Lean Body Mass Among Postmenopausal Women,” Journal of Clinical Endocrinology & Metabolism 85, no. 12 (2000): 4476–80.

369 biodentical products are delivered: Gail A. Greendale etal., “Symptom Relief and Side Effects of Postmenopausal Hormones,” Obstetrics o’ Gynecology 92, no.6 (1998); 982–88.

371 Perhaps the new or full moon can serve: Northrup, The Wisdom of Menopause.

377 If you stress lab rats: C. Pugh, et al “Role of Interleukin-1 Beta in Impairment of Contextual Fear Conditioning Caused by Social Isolation,” Behavioural Brain Research 106, no. 1 (1999): 109–18.

377 If you block the IL1-beta: R. M. Barrientos et al., “Brain-Derived Neurotrophic Factor Mrna Downregulation Produced by Social Isolation Is Blocked by Intrahippocampal Interleukin-1 Receptor Antagonist,” Neuroscience 121, no. 4 (2003): 847–53.

378 When the junk food is removed: Johnson et al., “Dopamine D2 Receptors in Addiction-like Reward Dysfunction,” 635–41.

379 Rats show they prefer saccharine-sweetened water: Magalie Lenoir et al., “Intense Sweetness Surpasses Cocaine Reward.” PloS One 2, no. 8 (2007): e698.

381 half the fat of coconut oil is lauric acid: Shari Lieberman et al., “A Review of Monolaurin and Lauric Acid: Natural Virucidal and Bactericidal Agents,” Alternative & Complementary Therapies 12, no. 6 (2006): 310–14.

383 Anxious patients are more deficient: Joanne J. Liu et al., “Omega-3 Polyunsaturated Fatty Acid (PUFA) Status in Major Depressive Disorder with Comorbid Anxiety Disorders,” Journal of Clinical Psychiatry 74, no. 7 (2013): 732–38.

383 those with more severe social anxiety disorders: Pnina Green et al., “Red Cell Membrane Omega-3 Fatty Acids Are Decreased in Nondepressed Patients with Social Anxiety Disorder,” European Neuropsychopharmacology 16, no. 2 (2006): 107–13.

383 supplementation decreases anxiety-like behaviors in rodents: Venugopal Reddy Venna et al., “PUFA Induce Antidepressant-like Effects in Parallel to Structural and Molecular Changes in the Hippocampus,” Psychoneuroendocrinology 34, no. 2 (2009): 199–211.

383 nonhuman primates: Nina Vinot et al., “Omega-3 Fatty Acids from Fish Oil Lower Anxiety, Improve Cognitive Functions and Reduce Spontaneous Locomotor Activity in a Non-Human Primate,” PLoS One 6, no. 6 (2011): e20491.

383 medical students: Janice K. Kiecolt-Glaser et al., “Omega-3 Supplementation Lowers Inflammation and Anxiety in Medical Students: A Randomized Controlled Trial,” Brain, Behavior, and Immunity 25, no. 8 (2011): 1725–34.

383 they need to be high in EPA: Liu et al., “Omega-3 Polyunsaturated Fatty Acid (PUFA) Status in Major Depressive Disorder,” The Journal of Clinical Psychiatry 174, no. 7, (2013): 732–38.

384 Chronic treatment with the bacteria: M. E. O’Brien et al., “SRL172 (Killed Mycobacterium Vaccae) in Addition to Standard Chemotherapy Improves Quality of Life Without Affecting Survival, in Patients with Advanced Non-Small-Cell Lung Cancer: Phase III Results,” Annals of Oncology 15, no. 6 (2004): 906–14.

384 reducing levels of cytokines: R. Hernandez-Pando and G. A. Rook, “The Role of TNF-Alpha in T-Cell-Mediated Inflammation Depends on the Th1/Th2 Cytokine Balance,” Immunology 82, no. 4 (1994): 591.

384 Treatment with bifidobacteria: J. Rao et al., “Regulation of Cerebral Glucose Metabolism,” Minerva ­Endocrinologica 31, no. 2 (2006): 149.

385 Endocannabinoids: Chu Chen and Nicolas G. Bazan, “Lipid Signaling: Sleep, Synaptic Plasticity, and Neuroprotection,” Prostaglandins & Other Lipid Mediators 77, no. 1 (2005): 65–76; Eric Murillo-­Rodriguez et al., “Anandamide Enhances Extracellular Levels of Adenosine and Induces Sleep: An in Vivo Microdialysis Study,” SLEEP 26, no. 8 (2003): 943–47.

386 In depressive disorders, insomnia is: Maurice M. Ohayon and Thomas Roth, “Place of Chronic Insomnia in the Course of Depressive and Anxiety Disorders,” Journal of Psychiatric Research (2003).

390 SSRIs are often used: M. P. Kafka, “Successful Antidepressant Treatment of Nonparaphilic Sexual Addictions and Paraphilias in Men,” Journal of Clinical Psychiatry 52 (1991): 60–65.

390 If you are on SSRIs and have the genotype: Jeffrey R. Bishop et al., “The Association of Serotonin Transporter Genotypes and Selective Serotonin Reuptake Inhibitor (SSRI)–Associated Sexual Side Effects: Possible Relationship to Oral Contraceptives,” Human Psychopharmacology: Clinical and Experimental 24, no. 3 (2009): 207–15.

390 Double-SERT people are more likely: G. L. Hanna et al., “Serotonin Transporter and Serotonin Transporter Promoter Affects Onset of Paroxetine Treatment Seasonal Variation in Blood Serotonin in Families With Obsessive-Compulsive Disorder,” Neuropsychopharmacology 18 (1998): 102–11.

390 better responders to SSRIs than double-S people: Nada Bozina et al., “Association Study of Paroxetine Therapeutic Response with SERT Gene Polymorphisms in Patients with Major Depressive Disorder,” World Journal of Biological Psychiatry 9, no. 3 (2008): 190–97.

390 In experiments, THC led to delayed time: T. L. Crenshaw and J. P. Goldberg, Sexual Pharmacology: Drugs That Affect Sexual Function (New York: Norton, 1996).

390 In the female rat, levels of brain endocannabinoids: Heather B. Bradshaw et al., “Sex and Hormonal Cycle Differences in Rat Brain Levels of Pain-Related Cannabimimetic Lipid Mediators,” American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 291, no. 2 (2006): R349–R358.

390 Female rats receiving an endocannabinoid antagonist: Hassan H.López et al., “Cannabinoid Receptor Antagonism Increases Female Sexual Motivation,” Pharmacology Biochemistry and Behavior 92, no. 1 (2009): 17–24.

390 if you stimulate pleasure centers chemically: James Olds and Peter Milner, “Positive Reinforcement Produced by Electrical Stimulation of Septal Area and Other Regions of Rat Brain,” Journal of Comparative and Physiological Psychology 47, no. 6 (1954): 419; Robeht G. Heath, “Depth Recording and Stimulation Studies in Patients,” Surgical Control of Behavior (1971): 21–37.

390 The dopamine and endorphin release: Doidge, The Brain That Changes Itself.

391 To insure against “poachers”: Ryan and Jethá, Sex at Dawn.

391 Even babies in the womb: Israel Meizner, “Sonographic Observation of in Utero Fetal ‘Masturbation,’    ” Journal of Ultrasound in Medicine 6, no. 2 (1987): 111; Harry Bakwin, “Erotic Feelings in Infants and Young Children,” Archives of Pediatrics & Adolescent Medicine 126, no. 1 (1973): 52.

391 Sexual pleasure from exercise: Debby Herbenick and J. Dennis Fortenberry, “Exercise-Induced Orgasm and Pleasure Among Women,” Sexual and Relationship Therapy 26, no. 4 (2011): 373–88.

392 fascinating research on just how the uterus contracts: G. Kunz et al., “Uterine Peristalsis During the Follicular Phase of the Menstrual Cycle: Effects of Estrogen, Antioestrogen and Oxytocin,” Human Reproduction Update 4, no. 5 (1998): 647–54.

392 all mediated by oxytocin: H. Newton, “The Role of the Oxytocin Reflexes in Three Interpersonal Reproductive Acts: Coitus, Birth and Breastfeeding,” Clinical Psychoneuroendocrinology in Reproduction 22 (1978): 411–18.

392 prosocial, trusting behaviors: P. Kirsch et al., “Oxytocin Modulates Neural Circuitry for Social Cognition and Fear in Humans,” Journal of Neuroscience 25, (2005): 11489–93.

394 hippocampal neuroplasticity: Zhen Zhang et al.,”Blockade of 2-Arachidonoylglycerol Hydrolysis Produces Antidepressant-Like Effects and Enhances Adult Hippocampal Neurogenesis And Synaptic Plasticity,” Hippocampus, August 27, 2014.

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