Sex, hormones, and genotype interact to influence psychiatric disease, treatment, and behavioral research

Journal of Neuroscience Research

Volumn 95, Issue 1-2, 2017, Pages 50-64

  Gobinath, Aarthi R ^a   Choleris, Elena ^b   Galea, Liisa A M ^a  

^a UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^b UNIVERSITY OF GUELPH   (Canada)

Author keywords

genotype; hormones; neurological diseases; psychiatric diseases; reproduction

Indexed keywords

SEX HORMONE;

AGING; BEHAVIORAL RESEARCH; DISEASE PREDISPOSITION; GENE INTERACTION; GENOTYPE; HUMAN; MENTAL DISEASE; MORBIDITY; NEUROSCIENCE; PHYSIOLOGY; PRIORITY JOURNAL; PSYCHIATRIC TREATMENT; PUBERTY; REPRODUCTIVE HEALTH; REVIEW; SEX; SEX DIFFERENCE; TREATMENT OUTCOME; ANIMAL; FEMALE; GENETICS; MALE; MENTAL DISORDERS; METABOLISM; SEXUAL DEVELOPMENT;

ANIMALS; BEHAVIORAL RESEARCH; FEMALE; GENOTYPE; GONADAL STEROID HORMONES; HUMANS; MALE; MENTAL DISORDERS; SEX CHARACTERISTICS; SEX FACTORS;

EID: 84994246264     PISSN: 03604012     EISSN: 10974547     Source Type: Journal    
DOI: 10.1002/jnr.23872     Document Type: Review

References (156)

1. Angst J, Gamma A, Gastpar M, Lepine JP, Mendlewicz J, Tylee A, Depression Research in European Society Study. 2002. Gender differences in depression. Epidemiological findings from the European DEPRES I and II studies. Eur Arch Psychiatry Clin Neurosci 252:201–209.
2. Arnold LM. 2003. Gender differences in bipolar disorder. Psychiatr Clin North Am 26:595–620.
3. Barha CK, Galea LA. 2011. Motherhood alters the cellular response to estrogens in the hippocampus later in life. Neurobiol Aging 32:2091–2095.
4. Baune BT, Hohoff C, Mortensen LS, Deckert J, Arolt V, Domschke K. 2008. Serotonin transporter polymorphism (5-HTTLPR) association with melancholic depression: a female specific effect? Depress Anxiety 25:920–925.
5. Becker JB, Cha JH. 1989. Estrous cycle-dependent variation in amphetamine-induced behaviors and striatal dopamine release assessed with microdialysis. Behav Brain Res 35:117–125.
6. Becker JB, Koob GF. 2016. Sex differences in animal models: focus on addiction. Pharmacol Rev 68:242–263.
7. Beckman LJ, Amaro H. 1986. Personal and social difficulties faced by women and men enterine alcoholism treatment. J Stud Alcohol 47:135–145.
8. Beery AK, Zucker I. 2011. Sex bias in neuroscience and biomedical research. Neurosci Biobehav Rev 35:565–572.
9. Bellott DW, Hughes JF, Skaletsky H, Brown LG, Pyntikova T, Cho TJ, Koutseva N, Zaghlul S, Graves T, Rock S, Kremitzki C, Fulton RS, Dugan S, Ding Y, Morton D, Khan Z, Lewis L, Buhay C, Wang Q, Watt J, Holder M, Lee S, Nazareth L, Alföldi J, Rozen S, Muzny DM, Warren WC, Gibbs RA, Wilson RK, Page DC. 2014. Mammilian Y chromosomes retain widely expressed dosage-sensitive regulators. Nature 508:494–499.
10. Bennett HA, Einarson A, Taddio A, Koren G, Einarson TR. 2004. Prevalence of depression during pregnancy: systematic review. Obstet Gynecol 103:698–709.
11. Bergemann N, Mundt C, Parzer P, Pakrasi M, Eckstein-Mannsperger U, Haisch S, Salbach B, Klinga K, Runnebaum B, Resch F. 2005. Estrogen as an adjuvant therapy to antipsychotics does not prevent relapse in women suffering from schizophrenia: results of a placebo-controlled double-blind study. Schizophr Res 74:125–134.
12. Bergemann N, Parzer P, Nagl I, Salbach B, Runnebaum B, Mundt C, Resch F. 2002. Acute psychiatric admission and menstrual cycle phase in women with schizophrenia. Arch Womens Ment Health 5:119–126.
13. Björkqvist K. 1994. Sex differences in physical, verbal, and indirect aggression: a review of recent research. Sex Roles 30:177–188.
14. Bottcher B, Radenbach K, Wildt L, Hinney B. 2012. Hormonal contraception and depression: a survey of the present state of knowledge. Arch Gynecol Obstet 286:231–236.
15. Brett M, Baxendale S. 2001. Motherhood and memory: a review. Psychoneuroendocrinology. 26:339–362.
16. Brunton PJ, Russell JA, Douglas AJ. 2008. Adaptive responses of the maternal hypothalamic-pituitary-adrenal axis during pregnancy and lactation. J Neuroendocrinol 20:764–776.
17. Bryant NL, Buchanan RW, Vladar K, Breier A, Rothman M. 1999. Gender differences in temporal lobe structures of patients with schizophrenia: a volumetric MRI study. Am J Psychiatry 156:603–609.
18. Button KS, Ioannidis JP, Mokrysz C, Nosek BA, Flint J, Robinson ES, Munafo MR. 2013. Power failure: why small sample size undermines the reliability of neuroscience. Nat Rev Neurosci 14:365–376.
19. Byrne SE, Rothschild AJ. 1998. Loss of antidepressant efficacy during maintenance therapy: possible mechanisms and treatments. J Clin Psychiatry 59:279–288.
20. Cahill L. 2014. Fundamental sex difference in human brain architecture. Proc Natl Acad Sci U S A 111:577–578.
21. Carlsson M, Carlsson A. 1988. A regional study of sex differences in rat brain serotonin. Prog Neuropsychopharmacol Biol Psychiatry 12:53–61.
22. Chapman RM, Mapstone M, Gardner MN, Sandoval TC, McCrary JW, Guilily MD, Reilly LA, DeGrush E. 2011. Women have father to fall: gender differences between normal elderly and Alzheimer's disease in verbal memory engender better detection of Alzheimer's disease in women. J Int Neuropsychol Soc 17:654–662.
23. Chekroud AM, Ward EJ, Rosenberg MD, Holmes AJ. 2016. Patterns in the human brain mosaic discriminate males from females. Proc Natl Acad Sci U S A 113:E1968.
24. Choleris E, Clipperton-Allen AE, Gray DG, Diaz-Gonzalez S, Welsman RG. 2011. Differential effects of dopamine receptor D1-type and D2-type antagonists and phase of the estrous cycle on social learning of food preferences, feeding, and social interactions in mice. Neuropsychopharmaoclogy 36:1689–1702.
25. Clayton JA, Collins FS. 2014. Policy: NIH to balance sex in cell and animal studies. Nature 509:282–283.
26. Clipperton AE, Spinato JM, Chernets C, Pfaff DW, Choleris E. 2008. Differential effects of estrogen receptor alpha and beta specific agonists on social learning of food preferences in female mice. Neuropsychopharmacology 33:2362–2375.
27. Clipperton-Allen AE, Cragg CL, Wood AJ, Pfaff DW, Choleris E. 2010. Agonistic behavior in males and females: effects of an estrogen receptor beta agonist in gonadectomized and gonadally intact mice. Psychoneuroendocrinology 35:1008–1022.
28. Clipperton-Allen AE, Almey A, Melichercik A, Allen CP, Choleris E. 2011. Effects of an estrogen receptor alpha agonist on agonistic behaviour in intact and gonadectomized male and female mice. Psychoneuroendocrinology 36:981–995.
29. Coppen A, Bailey J. 2000. Enhancement of the antidepressant action of fluoxetine by folic acid: a randomised, placebo controlled trial. J Affect Disord 60:121–130.
30. Crawford MB, DeLisi LE. 2016. Issues related to sex differences in antipsychotic treatment. Curr Opin Psychiatry:29:211–217.
31. Dagg AI. 1984. Homosexual behavior and female–male mounting in mammals—a first survey. Mammal Rev 14:155–185.
32. Dalla C, Antoniou K, Drossopoulou G, Xagoraris M, Kokras N, Sfikakis A, Papadopoulou-Daifoti Z. 2005. Chronic mild stress impact: are females more vulnerable? Neuroscience 135:703–714.
33. Dalla C, Pitychoutis PM, Kokras N, Papadopoulou-Daifoti Z. 2010. Sex differences in animal models of depression and antidepressant response. Basic Clin Pharmacol Toxicol 106:226–233.
34. Damoiseaux VA, Proost JH, Jiawan VC, Melgert BN. 2014. Sex differences in the pharmacokinetics of antidepressants: influence of female sex hormones and oral contraceptives. Clin Pharmacokinet 53:509–519.
35. De Almeida RM, Cabral JC, Narvaes R. 2015. Behavioural, hormonal and neurobiological mechanisms of aggressive behaviour in human and nonhuman primates. Physiol Behav 143:121–135.
36. De Crescenzo F, Perelli F, Armando M, Vicari S. 2014. Selective serotonin reuptake inhibitors (SSRIs) for post-partum depression (PPD): a systematic review of randomized clinical trials. J Affect Disord 152–154:39–44.
37. De Vries GJ, Forger NG. 2015. Sex differences in the brain: a whole body perspective. Biol Sex Differ 6:15.
38. Del Giudice M, Lippa RA, Puts DA, Bailey DH, Bailey JM, Schmitt DP. 2016. Joel et al.'s method systematically fails to detect large, consistent sex differences. Proc Natl Acad Sci U S A 113:E1965.
39. Diver MJ, Imtiaz KE, Ahmad AM, Vora JP, Fraser WD. 2003. Diurnal rhythms of serum total, free and bioavailable testosterone and of SHBG in middle-aged men compared with those in young men. Clin Endocrinol 58:710–717.
40. Ellegren H, Parsch J. 2007. The evolution of sex-biased genes and sex-biased gene expression. Nat Rev Genet 8:689–698.
41. Epp JR, Beasley CL, Galea LA. 2013. Increased hippocampal neurogenesis and p21 expression in depression: dependent on antidepressants, sex, age, and antipsychotic exposure. Neuropsychopharmacology 38:2297–2306.
42. Ervin KS, Mulvale E, Gallagher N, Roussel V, Choleris E. 2015. Activation of the G protein-coupled estrogen receptor, but not estrogen receptor a or B, rapidly enhnces social learning. Psychoneuroendocrinology 58:51–66.
43. Ferguson JM, Hill H. 2006. Pharmacokinetics of fluoxetine in elderly men and women. Gerontology 52:45–50.
44. Fernandez-Guasti A, Olivares-Nazario M Reyes R, Marinez-Mota L. 2016. Sex and age differences in the antidepressant-like effect of fluoxetine in the forced swim test. Pharmacol Biochem Behav pii:S0091-3057(16)30010-30017. doi: 10.1016/j.pbb.2016.01.011
45. Ferrari PF, Palanza P, Rodgers RJ, Mainardi M, Parmigiani S. 1996. Comparing different forms of male and female aggression in wild and laboratory mice: an ethopharmacological study. Physiol Behav 60:549–553.
46. Fombonne E. 2009. Epidemiology of pervasive developmental disorders. Pediatr Res 65:591–598.
47. Forger NG. 2006. Cell death and sexual differentiation of the nervous system. Neuroscience 138:929–938.
48. Frodl T, Meisenzahl EM, Zetzsche T, Born C, Groll C, Jager M, Leinsinger G, Bottlender R, Hahn K, Moller HJ. 2002. Hippocampal changes in patients with a first episode of major depression. Am J Psychiatry 159:1112–1118.
49. Galea LA, Wide JK, Barr AM. 2001. Estradiol alleviates depressive-like symptoms in a novel animal model of postpartum depression. Behav Brain Res:122:1–9.
50. Gartlehner G, Chapman A, Strobelberger M, Thaler K. 2010. Differences in efficacy and safety of pharmaceutical treatments between men and women: an umbrella review. PLoS One 5:e11895.
51. Gavin NI, Gaynes BN, Lohr KN, Meltzer-Brody S, Gartlehner G, Swinson T. 2005. Perinatal depression: a systematic review of prevalence and incidence. Obstet Gynecol 106:1071–1083.
52. Ge X, Conger RD, Elder GH Jr. 2001. Pubertal transition, stressful life events, and the emergence of gender differences in adolescent depressive symptoms. Dev Psychol 37:404–417.
53. Glezerman M. 2016. Yes, there is a female and a male brain: morphology versus functionality. Proc Natl Acad Sci U S A 113:E1971.
54. Gold PW. 2015. The organization of the stress system and its dysregulation in depressive illness. Mol Psychiatry 20:32–47.
55. Goldstein JM, Seidman LJ, Goodman JM, Koren D, Lee H, Weintraub S, Tsuang MT. 1998. Are there sex differences in neuropsychological functions among patients with schizophrenia? Am J Psychiatry 155:1358–1364.
56. Goldstein JM, Cohen LS, Horton NJ, Lee H, Andersen S, Tohen M, Crawford A, Tollefson G. 2002. Sex differences in clinical response to olanzaine compared with haloperidol. Psychiatry Res 110:27–37.
57. Goldstein RB, Dawson DA, Chou SP, Grant BF. 2012. Sex differences in prevalence and comorbidity of alcohol and drug use disorders: results from wave 2 of the National Epidemiological Survey on Alcohol and Related Conditions. J Stud Alcohol Drugs 73:938–950.
58. Grant EC, Mackintosh JH. 1963. A comparison of the social postures of some common laboratory rodents. Behaviour 21:246–259.
59. Greenblatt DJ, Harmatz JS, Singh NN, Steinberg F, Roth T, Moline ML, Harris SC, Kapil RP. 2014. Gender differences in pharmacokinetics and pharmacodynamics of zolpidem following sublingual administration. J Clin Pharmacol 54:282–290.
60. Gruene TM, Roberts E, Thomas V, Ronzio A, Shansky RM. 2015a. Sex-specific neuroanatomical correlates of fear expression in prefrontal-amygdala circuits. Biol Psychiatry 78:186–193.
61. Gruene TM, Flick K, Stefano A, Shea SD, Shansky RM. 2015b. Sexually divergent expression of active and passive conditioned fear responses in rats. Elife 2015:4. pii:e11352.
62. Han M, Huang XF, Chen Da C, Xiu MH, Hui L, Liu H, Kosten TR, Zhang XY. 2012. Gender differences in cognitive function of patients with chronic schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 39:358–363.
63. Heils A, Teufel A, Petri S, Stober G, Riederer P, Bengel D, Lesch KP. 1996. Allelic variation of human serotonin transporter gene expression. J Neurochem 66:2621–2624.
64. Hendrick V, Altshuler LL, Suri R. 1998. Hormonal changes in the postpartum and implications for postpartum depression. Psychosomatics 39:93–101.
65. Hildebrandt MG, Stage KB, Kragh-Soerensen P, Danish University Antidepressant Group. 2003. Gender differences in severity, symptomatology and distribution of melancholia in major depression. Psychopathology 36:204–212.
66. Hilli J, Korhonen T, Turpeinen M, Hokkanen J, Mattila S, Laine K. 2008. The effect of oral contraceptives on the pharmacokinetics of melatonin in healthy subjects with CYP1A2 g.–163C>A polymorphism. J Clin Pharmacol 48:986–994.
67. Hodes GE, Hill-Smith TE, Suckow RF, Cooper TB, Lucki, I. 2010. Sex-specific effects of chronic fluoxetine treatment on neuroplasticity and pharmacokinetics in mice. J Pharmacol Exp Ther 332:266–273.
68. Holland J, Bandelow S, Hogervorst E. 2011. Testosterone levels and cognition in elderly men: a review. Maturitas 69:322–337.
69. Idring S, Lundberg M, Sturm H, Dalman C, Gumpert C, Rai D, Lee BK, Magnusson C. 2015. Changes in prevalence of autism spectrum disorders in 2001–2011: findings from the Stockholm youth cohort. J Autism Dev Disord 45:1766–1773.
70. Inagaki T, Miyaoka T, Tsuji S, Inami Y, Nishida A, Horiguchi J. 2010. Adverse reactions to zolpidem: case reports and a review of the literature. Prim Care Companion J Clin Psychiatry. 12(6). pii: PCC. 09r00849. doi: 10.4088/PCC.09r00849bro
71. Ingalhalikar M, Smith A, Parker D, Satterthwaite TD, Elliott MA, Ruparel K, Hakonarson H, Gur RE, Gur RC, Verma R. 2014. Sex differences in the structural connectome of the human brain. Proc Natl Acad Sci U S A 111:823–828.
72. Irvine K, Laws KR, Gale TM, Kondel TK. 2012. Greater cognitive detrioration in women than men with Alzheimer's disease: a meta analysis. J Clin Exp Neuropsychol 34:989–998.
73. Joel D. 2011. Male or female? Brains are intersex. Front Integr Neurosci 5:57.
74. Joel D, Berman Z, Tavor I, Wexler N, Gaber O, Stein Y, Shefi N, Pool J, Urchs S, Margulies DS, Liem F, Hanggi J, Jancke L, Assaf Y. 2015. Sex beyond the genitalia: The human brain mosaic. Proc Natl Acad Sci U S A 112:15468–15473.
75. Josefsson A, Sydsjo G. 2007. A follow-up study of postpartum depressed women: recurrent maternal depressive symptoms and child behavior after four years. Arch Womens Ment Health 10:141–145.
76. Jovanovic H, Lundberg J, Karlsson P, Cerin A, Saijo T, Varrone A, Halldin C, Nordstrom AL. 2008. Sex differences in the serotonin 1A receptor and serotonin transporter binding in the human brain measured by PET. Neuroimage 39:1408–1419.
77. Kawa I, Carter JD, Joyce PR, Doughty CJ, Frampton CM, Wells JE, Walsh AE, Olds RJ. 2005. Gender differences in bipolar disorder: age of onset, course, comorbidity, and symptom presesntation. Bipolar Disord 7:199–125.
78. Keers R, Aitchison KJ. 2010. Gender differences in antidepressant drug response. Int Rev Psychiatry 22:285–500.
79. Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE. 2005. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 62:593–602.
80. Keyes KM, Cheslack-Postava K, Westhoff C, Heim CM, Haloossim M, Walsh K, Koenen K. 2013. Association of hormonal contraceptive use with reduced levels of depressive symptoms: a national study of sexually active women in the United States. Am J Epidemiol 178:1378–1388.
81. Keyes K, Agnew-Blais J, Roberts AL, Hamilton A, De Vivo I, Ranu H, Koenen K. 2015. The role of allelic variation in estrogen receptor genes and major depression in the Nurses Health Study. Soc Psychiatry Psychiatr Epidemiol 50:1893–1904.
82. Kitamura T, Kitamura M, Hino S, Tanaka N, Kurata K. 2012. Gender differences in clinical manifestations and outcomes among hospitalized atients with behavioral and psychological symptoms of dementia. J Clin Psychiatry 73:1548–1554.
83. Kokras N, Dalla C, Papadopoulou-Daifoti Z. 2011. Sex differences in pharmacokinetics of antidepressants. Expert Opin Drug Metab Toxicol 7:213–226.
84. Kokras N, Polissidis A, Antoniou K, Dalla C. 2016. Head shaking in the forced swim test: A robust but unexplored sex difference. Pharmacol Biochem Behav pii:S0091-3057(16)30097-1. doi: 10.1016/j.pbb.2016.05.007 [E-pub ahead of print].
85. Kucuk AI, Atalay C. 2012. The relationship between surgery and phase of the menstrual cycle affects survival in breast cancer. J Breast Cancer 15:434–440.
86. Lamers F, Vogelzangs N, Merikangas KR, De Jonge P, Beekman AT, Penninx BW. 2013. Evidence for a differential role of HPA-axis function, inflammation and metabolic syndrome in melancholic versus atypical depression. Mol Psychiatry 18:692–699.
87. Laws KR, Duncan A, Gale TM. 2010. “Normal” semantic–phonemic fluency discrepancy in Alzheimer's disease? A meta-analytic study. Cortex 46:595–601.
88. Leung A, Chue P. 2000. Sex differences in schizophrenia, a review of the literature. Acta Psychiatr Scand Suppl 401:3–38.
89. Ley-Ran S, Le Strat Y, Imtiaz S, Rehm J, Le Foll B. 2013. Gender differences in prevalence of substance use disorders among individuals with lifetime exposure to substances: results from a large representative sample. Am J Addict 22:7–13.
90. Mahmoud R, Wainwright SR, Chaiton JA, Lieblich SE, Galea LA. 2016. Ovarian hormones, but not fluoxetine, impart resilience within a chronic unpredictable stress model in middle-aged female rats. Neuropharmacology 107:278–293.
91. Mahmoud R, Wainwright SR, Galea LA. 2016. Sex hormones and adult hippocampal neurogenesis: regulation, implications, and potential mechanisms. Front Neuroendocrinol 41:129–152.
92. Marazziti D, Baroni S, Picchetti M, Piccinni A, Carlini M, Vatteroni E, Falaschi V, Lombardi A, Dell'Osso L. 2013. Pharmacokinetics and pharmacodynamics of psychotropic drugs: effects of sex. CNS Spectr 18:118–127.
93. McCarthy MM. 2015. Incorporating sex a a variable in preclinical neuropsychiatric research. Schizophr Bull 41:1016–1020.
94. McCarthy MM, Arnold AP, Ball GF, Blaustein JD, De Vries GJ. 2012. Sex differences in the brain: the not so inconvenient truth. J Neurosci 32:2241–2247.
95. McDonald JH. 2014. Handbook of biological statistics, 3rd ed. Baltimore: Sparky House Publishing.
96. McKinnon MC, Yucel K, Nazarov A, Macqueen GM. 2009. A meta-analysis examining clinical predictors of hippocampal volume in patients with major depressive disorder. J Psychiatry Neurosci 34:41–54.
97. Mefford J, Witte JS. 2012. The covariate's dilemma. PLoS Genet 8:e1003096.
98. Mirowska-Guzel D, Gromadzka G, Mendel T, Janus-Laszuk B, Dzierka J, Sarzynska-Dlugosz I, Czlonkowski A, Czlonkowska A. 2014. Impact of BDNF –196 G>A and BDNF –270 C>T polymorphisms on stroke rehabilitation outcome: sex and age differences. Top Stroke Rehabil 21(Suppl 1):S33–S41.
99. Moffat SD, Hampson E. 2000. Salivary testosterone concentrations in left-handers: an association with cerebral language lateralization? Neuropsychology 14:71–81.
100. Nishizawa S, Benkelfat C, Young SN, Leyton M, Mzengeza S, De Montigny C, Blier P, Diksic M. 1997. Differences between males and females in rates of serotonin synthesis in human brain. Proc Natl Acad Sci U S A 94:5308–5313.
101. O'Hara MW, Mccabe JE. 2013. Postpartum depression: current status and future directions. Annu Rev Clin Psychol 9:379–407.
102. Oatridge A, Holdcroft A, Saeed N, Hajnal JV, Puri BK, Fusi L, Bydder GM. 2002. Change in brain size during and after pregnancy: study in healthy women and women with preeclampsia. AJNR Am J Neuroradiol 23:19–26.
103. Oberlander JG, Woolley CS. 2016. 17Beta-estradiol acutely potentiates glutamatergic synaptic transmission in the hippocampus through distinct mechanisms in males and females. J Neurosci 36:2677–2690.
104. Ochoa S, Usall J, Cobo J, Labad X, Kulkarni J. 2012. Gender differences in schizophrenia and first-episode psychosis: a comprehensive literature review. Schizophr Res Treatment 2012:916198.
105. Ossenkopp KP, Rabi YJ, Eckel LA. 1996. Oestradiol-induced taste avoidance is the result of a conditioned palatability shift. Neuroreport 7:2777–2780.
106. Palanza P, Parmigianim S. 1994. Functional analysis of maternal aggression in the house mouse (Mus musculus domesticus). Behav Process 32:1–16.
107. Parmigiani S, Ferrari PF, Palanza P. 1998. An evolutionary approach to behavioral pharmacology: using drugs to understand proximate and ultimate mechanisms of different forms of aggression in mice. Neurosci Biobehav Rev 23:143–153.
108. Porcelli S, Fabbri C, Serretti A. 2012. Meta-analysis of serotonin transporter gene promoter polymorphism (5-HTTLPR) association with antidepressant efficacy. Eur Neuropsychopharmacol 22:239–258.
109. Ptok U, Barkow K, Heun R. 2002. Fertility and number of children in patients with Alzheimer's disease. Arch Womens Ment Health 5:83–86.
110. Ramtekkar UP, Reiersen AM, Todorov AA, Todd RD. 2010. Sex and age differences in attention-deficit/hyperactivity disorder symptoms and diagnoses: implications for DSM-V and ICD-11. J Am Acad Child Adolesc Psychiatry 49:217–228, e211–e213.
111. Robertson E, Grace S, Wallington T, Stewart DE. 2004. Antenatal risk factors for postpartum depression: a synthesis of recent literature. Gen Hosp Psychiatry 26:289–295.
112. Rucklidge JJ. 2010. Gender differences in attention–deficit/hyperactivity disorder. Psychiatr Clin North Am 33:357–373.
113. Ruigrok AN, Salimi-Khorshidi G, Lai MC, Baron-Cohen S, Lombardo MV, Tait RJ, Suckling J. 2014. A meta-analysis of sex differences in human brain structure. Neurosci Biobehav Rev 39:34–50.
114. Ruitenberg A, Ott A, Van Swieten JC, Hofman A, Breteler MM. 2001. Incidence of dementia: does gender make a difference? Neurobiol Aging 22:575–580.
115. Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, Niederehe G, Thase ME, Lavori PW, Lebowitz BD, McGrath PJ, Rosenbaum JF, Sackeim HA, Kupfer DJ, Luther J, Fava M. 2006. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry:163:1905–1917.
116. Sanchez-Andrade G, James BM, Kendrick KM. 2005. Neural encoding of olfactory recognition memory. J Reprod Dev 51:547–558.
117. Scacchi R, Gambina G, Broggio E, Corbo RM. 2014. Sex and ESR1 genotype may influence the response to treatment with donepezil and rivastigimine in patients with Alzheimer's disease. Int J Geriatr Psychiatry 29:610–615.
118. Schoning S, Engelien A, Kugel H, Schafer S, Schiffbauer H, Zwitserlood P, Pletziger E, Beizai P, Kersting A, Ohrmann P, Greb RR, Lehmann W, Heindel W, Arolt V, Konrad C. 2007. Functional anatomy of visuo-spatial working memory during mental rotation is influenced by sex, menstrual cycle, and sex steroid hormones. Neuropsychologia 45:3203–3214.
119. Schuch JJ, Roest AM, Nolen WA, Penninx BW, De Jonge P. 2014. Gender differences in major depressive disorder: results from The Netherlands study of depression and anxiety. J Affect Disord 156:156–163.
120. Scott JP, Fredericson E. 1951. The causes of fighting in mice and rats. Physiol Zool 24:273–309.
121. Shen EY, Ahern TH, Cheung E, Straubhaar J, Dincer A, Houston I, de Vries GJ, Akbarian S, Forger NG. 2015. Epigenetics and sex differences in the brain: a genome-wide comparison of histone-3 lysine-4 trimethylation (H3K4me3) in male and female mice. Exp Neurol 268:21–29.
122. Soldin OP, Mattison DR. 2009. Sex differences in pharmacokinetics and pharmacodynamics. Clin Pharmacokinet 48:143–157.
123. Sprout Pharmaceuticals, Inc. 2015. NDA 22526 Addyi (flibanserin; s serotonin 1A receptor agonist and a serotonin 2A receptor antagonist).
124. Steiner M, Dunn E, Born L. 2003. Hormones and mood: from menarche to menopause and beyond. J Affect Disord 74:67–83.
125. Straface E, Gambardella L, Brandani M, Malorni W. 2012. Sex differences at cellular level: “cells have a sex.” Handb Exp Pharmacol 2012:49–65.
126. Tan A, Ma W, Vira A, Marwha D, Eliot L. 2016. The human hippocampus is not sexually-dimorphic: meta-analysis of structural MRI volumes. Neuroimage 124:350–366.
127. Tannenbaum C, Schwarz JM, Clayton JA, de Vries GJ, Sullivan C. 2016. Evaluting sex as a biological variable in preclinical research: the dvevil in the details. Biol Sex Differ 7:13.
128. Thase ME, Entsuah R, Cantillon M, Kornstein SG. 2005. Relative antidepressant efficacy of venlafaxine and SSRIs: sex–age interactions. J Womens Health 14:609–616.
129. Thompson TL, Moss RL. 1997. Modulation of mesolimbic dopaminergic activity over the rat estrous cycle. Neurosci Lett 229:145–148.
130. Trivedi MH, Rush AJ, Wisniewski SR, Nierenberg AA, Warden D, Ritz L, Norquist G, Howland RH, Lebowitz B, McGrath PJ, Shores-Wilson K, Biggs MM, Balasubramani GK, Fava M. 2006. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry 163:28–40.
131. Usall J, Suarez D, Haro JM, SOHO Study Group. 2007. Gender differences in response to antipsychotic treatment in outpatients with schizophrenia. Psychiatry Res 153:225–231.
132. U.S. Department of Justice—Federal Bureau of Investigation. 2015. Crime in the United States. 2014. Table 42: Arrests, by sex, 2014. https://www.fbi.gov/about-us/cjis/ucr/crime-in-the-u.s/2014/crime-in-the-u.s.-2014/persons-arrested/main
133. U.S. Food and Drug Administration. 2013. FDA Drug Safety Communication: risk for next-morning impairment after use of insomnia drugs; FDA requires lower recommended doses for certain drugs containing zolpidem (Ambien, Ambien CR, Edluar, and Zolpimist).
134. U.S. Food and Drug Administration. 2014. How evaluation of sex-specific data in medical device clinical studies.
135. Vaillancourt T. 2013. Do human females use indirect aggression as an intrasexual competition strategy? Philos Trans R Soc Lond B Biol Sci 368:20130080.
136. Vakili K, Pillay SS, Lafer B, Fava M, Renshaw PF, Bonello-Cintron CM, Yurgelun-Todd DA. 2000. Hippocampal volume in primary unipolar major depression: a magnetic resonance imaging study. Biol Psychiatry 47:1087–1090.
137. Valenstein ES, Kakolewski JW, Cox VC. 1967. Sex differences in taste preference for glucose and saccharin solution. Science 156:942–943.
138. Van Den Eeden SK, #Tanner CM, Bernstein AL, Fross RD, Leimpeter A, Bloch DA, Nelson LM. 2003. Incidence of Parkinson's disease: variation by age, gender, and race/ethnicity. Am J Epidemiol 157:1015–1022.
139. Veening JG, Coolen LM, Gerrits PO. 2014. Neural mechanisms of female sexual behavior in the rat; comparison with male ejaculatory control. Pharmacol Biochem Behav 121:16–30.
140. Verhagen M, Van Roekel E, #Engels RC. 2014. Involvement of the BDNF gene in loneliness in adolescence: a report of opposite gene effects in boys and girls. PLoS One 9:e92768.
141. Wainwright SR, Barha CK, Hamson DK, Epp JR, Chow C, Lieblich SE, Rutishauser U, Galea LA. 2016. Enzymatic depletion of the polysialic acid moiety associated with the neural cell adhesion molecule inhibits antidepressant efficacy. Neuropsychopharmacology 41:1670–1680.
142. Wei SM, Eisenberg DP, Kohn PD, Kippenhan JS, Kolachana BS, Weinberger DR, Berman KF. 2012. Brain-derived neurotrophic factor Val(6)(6)Met polymorphism affects resting regional cerebral blood flow and functional connectivity differentially in women versus men. J Neurosci 32:7074–7081.
143. Werling DM, Geschwind DH. 2013. Understanding sex bias in autism spectrum disorder. Proc Natl Acad Sci U S A 110:4868–4869.
144. Wisner KL, Sit DK, Mcshea MC, Rizzo DM, Zoretich RA, Hughes CL, Eng HF, Luther JF, Wisniewski SR, Costantino ML, Confer AL, Moses-Kolko EL, Famy CS, Hanusa BH. 2013. Onset timing, thoughts of self-harm, and diagnoses in postpartum women with screen-positive depression findings. JAMA Psychiatry 70:490–498.
145. Woolley CS, Gould E, Frankfurt M, Mcewen BS. 1990. Naturally occurring fluctuation in dendritic spine density on adult hippocampal pyramidal neurons. J Neurosci 10:4035–4039.
146. Wooten GF, Currie LJ, Bovbjerg VE, Lee JK, Patrie J. 2004. Are men at greater risk for Parkinson's disease than women? J Neurol Neurosurg Psychiatry 75:637–639.
147. Workman JL, Gobinath AR, Kitay NF, Chow C, Brummelte S, Galea LA. 2016. Parity modifies the effects of fluoxetine and corticosterone on behavior, stress reactivity, and hippocampal neurogenesis. Neuropharmacology 105:443–453.
148. World Health Organization. 2008. The global burden of disease: 2004 update. Geneva: World Health Organization.
149. Wright DW, Kellermann AL, Hertzberg VS, Clark PL, Frankel M, Goldstein FC, Salomone JP, Dent LL, Harris OA, Ander DS, Lowery DW, Patel MM, Denson DD, Gordon AB, Wald MM, Gupta S, Hoffman SW, Stein DG. 2007. ProTECT: a randomized clinical trial of progesterone for acute traumatic brain injury. Ann Emerg Med 49:391–402, e391–e392.
150. Wright DW, Espinoza TR, Merck LH, Ratcliff JJ, Backster A, Stein DG. 2014. Gender differences in neurological emergencies part II: a consensus summary and research agenda on traumatic brain injury. Acad Emerg Med 21:1414–1420.
151. Xiao G, Wei J, Yan W, Wang W, Lu Z. 2008. Improved outcomes from the administration of progesterone for patients with acute severe traumatic brain injury: a randomized controlled trial. Crit Care 12:R61.
152. Young EA, Kornstein SG, Marcus SM, Harvey AT, Warden D, Wisniwski SR, Balasubramani GK, Fava M, Trivedi MH, John Rush A. 2009. Sex differences in response to citalopram: a STAR*D report. J Psychiatr Res 43:503–511.
153. Young SN, Ghadirian AM. 1989. Folic acid and psychopathology. Prog Neuropsychopharmacol Biol Psychiatry 13:841–863.
154. Zhou DF, Wu CS, Qi H, Fan JH, Sun XD, Como P, Qiao YL, Zhang L, Kieburtz K. 2006. Prevalence of dementia in rural China: impact of age, gender and education. Acta Neurol Scand 114:273–280.
155. Zirkin BR, Tenover JL. 2012. Aging and declining testosterone: past, present, and hopes for the future. J Androl 33:1111–1118.
156. Zuidema SU, de Jonghe JF, Verhey FR, Koopmans RT. 2009. Predictors of neuropsychiatric symptoms in nursing home patients: influence of gender and dementia severity. Int J Geriatr Psychiatry 24:1079–1086.