Sex differences in the brain, behavior, and neuropsychiatric disorders

Neuroscientist

Volumn 16, Issue 5, 2010, Pages 550-565

  Bao, Ai Min ^a   Swaab, Dick F ^b  

^a ZHEJIANG UNIVERSITY SCHOOL OF MEDICINE   (China)

^b NETHERLANDS INSTITUTE FOR NEUROSCIENCE   (Netherlands)

Author keywords

depression; gender identity; sex difference; sexual orientation; stress

Indexed keywords

ANDROGEN RECEPTOR; CORTICOTROPIN RELEASING FACTOR; SEX HORMONE; TESTOSTERONE; VASOACTIVE INTESTINAL POLYPEPTIDE;

ADULT; AGED; AGING; ALZHEIMER DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; ANENCEPHALUS; ANOREXIA; ANXIETY DISORDER; ATTENTION DEFICIT DISORDER; AUTISM; BEHAVIOR; BEHAVIOR DISORDER; BRAIN; BRAIN DEVELOPMENT; BRAIN DISEASE; BULIMIA; CASTRATION; CLINICAL ARTICLE; COGNITION; COPING BEHAVIOR; DEMENTIA; DEPRESSION; DYSLEXIA; DYSTHYMIA; FEMALE; GENDER IDENTITY; GILLES DE LA TOURETTE SYNDROME; HORMONE ACTION; HUMAN; HYPERACTIVITY; HYPNIC HEADACHE; HYPONATREMIA; HYPOPHYSITIS; HYPOTHALAMUS; HYPOTHALAMUS HYPOPHYSIS ADRENAL SYSTEM; KALLMANN SYNDROME; LEARNING DISORDER; MAJOR DEPRESSION; MALE; MENTAL DISEASE; MULTIPLE SCLEROSIS; NEUROLOGIC DISEASE; NUCLEAR MAGNETIC RESONANCE IMAGING; PEDOPHILIA; POSITRON EMISSION TOMOGRAPHY; POSTMENOPAUSE; POSTOPERATIVE COMPLICATION; POSTTRAUMATIC STRESS DISORDER; PRECOCIOUS PUBERTY; PREMENOPAUSE; PRENATAL DEVELOPMENT; PREOPTIC NUCLEUS; PRIORITY JOURNAL; RETT SYNDROME; REVIEW; SCHIZOPHRENIA; SENILE DEMENTIA; SEX DIFFERENCE; SEX DIFFERENTIATION; SEXUAL ORIENTATION; SLEEP APNEA SYNDROME; SLEEP DISORDER; SOCIAL ENVIRONMENT; STRESS; STRIA TERMINALIS; STUTTERING; SUBSTANCE ABUSE; THALAMUS MIDLINE NUCLEUS; TRANSSEXUALISM; WHIPLASH INJURY;

ANIMALS; BRAIN; FEMALE; HUMANS; MALE; MENTAL DISORDERS; SEX CHARACTERISTICS; SEX DETERMINATION PROCESSES; SEXUAL BEHAVIOR;

EID: 77957571306     PISSN: 10738584     EISSN: 10894098     Source Type: Journal    
DOI: 10.1177/1073858410377005     Document Type: Review

References (70)

1. Alexander GM, Hines M. 2002. Sex differences in response to childrenĝ€™s toys in nonhuman primates (Cercopithecus aethiops sabaeus). Evol Hum Behav 23: 467-479.
2. Alexander GM, Wilcox T., Woods R. 2009. Sex differences in infantsĝ€™ visual interest in toys. Arch Sex Behav 38: 427-433.
3. Allen LS, Gorski RA 1992. Sexual orientation and the size of the anterior commissure in the human brain. Proc Natl Acad Sci U S A 89: 7199-7202.
4. Allen LS, Hines M., Shryne JE, Gorski RA 1989. Two sexually dimorphic cell groups in the human brain. J Neurosci 9: 497-506.
5. Bao AM, Fischer DF, Wu YH, Hol EM, Balesar R., Unmehopa UA, and others. 2006. A direct androgenic involvement in the expression of human corticotropin-releasing hormone. Mol Psychiatry 11: 567-576.
6. Bao AM, Hestiantoro A., Van Someren EJ, Swaab DF, Zhou JN 2005. Colocalization of corticotropin-releasing hormone and oestrogen receptor-alpha in the paraventricular nucleus of the hypothalamus in mood disorders. Brain 128: 1301-1313.
7. Bao AM, Ji YF, Van Someren EJ, Hofman MA, Liu RY, Zhou JN 2004. Diurnal rhythms of free estradiol and cortisol during the normal menstrual cycle in women with major depression. Horm Behav 45: 93-102.
8. Bao AM, Meynen G., Swaab DF 2008. The stress system in depression and neurodegeneration: focus on the human hypothalamus. Brain Res Rev 57: 531-553.
9. Bao AM, Swaab DF 2007. Gender difference in age-related number of corticotropin-releasing hormone-expressing neurons in the human hypothalamic paraventricular nucleus and the role of sex hormones. Neuroendocrinology 85: 27-36.
10. Berglund H., Lindstrom P., Dhejne-Helmy C., Savic I. 2008. Male-to-female transsexuals show sex-atypical hypothalamus activation when smelling odorous steroids. Cereb Cortex 18: 1900-1908.
11. Bocklandt S., Horvath S., Vilain E., Hamer DH 2006. Extreme skewing of X chromosome inactivation in mothers of homosexual men. Hum Genet 118: 691-694.
12. Bocklandt S., Vilain E. 2007. Sex differences in brain and behavior: hormones versus genes. Adv Genet 59: 245-266.
13. Cantor JM, Kabani N., Christensen BK, Zipursky RB, Barbaree HE, Dickey R., and others. 2008. Cerebral white matter deficiencies in pedophilic men. J Psychiatr Res 42: 167-183.
14. Caseras X., Mataix-Cols D., An SK, Lawrence NS, Speckens A., Giampietro V., and others. 2007. Sex differences in neural responses to disgusting visual stimuli: implications for disgust-related psychiatric disorders. Biol Psychiatry 62: 464-471.
15. Chung WC, De Vries GJ, Swaab DF 2002. Sexual differentiation of the bed nucleus of the stria terminalis in humans may extend into adulthood. J Neurosci 22: 1027-1033.
16. Colapinto J. 2000. As nature made him: the boy who was raised as a girl. New York: HarperCollins.
17. Connelan J., Baron-Cohen S., Wheelwright S., Batki A., Ahluwalia J. 2000. Sex differences in human neonatal social perception. Infant Behav Dev 23: 113-118.
18. Coolidge FL, Thede LL, Young SE 2002. The heritability of gender identity disorder in a child and adolescent twin sample. Behav Genet 32: 251-257.
19. Dessens AB, Cohen-Kettenis PT, Mellenbergh GJ, vd Poll N., Koppe JG, Boer K. 1999. Prenatal exposure to anticonvulsants and psychosexual development. Arch Sex Behav 28: 31-44.
20. Dewing P., Shi T., Horvath S., Vilain E. 2003. Sexually dimorphic gene expression in mouse brain precedes gonadal differentiation. Brain Res Mol Brain Res 118: 82-90.
21. Diamond M., Sigmundson HK 1997. Sex reassignment at birth. Long-term review and clinical implications. Arch Pediatr Adolesc Med 151: 298-304. (Pubitemid 27133214)
22. Flisher AJ, Ziervogel CF, Chalton DO, Leger PH, Robertson BA 1993. Risk-taking behaviour of Cape Peninsula high-school students. Part VI. Road-related behaviour. S Afr Med J 83: 486-490.
23. Gaffney GR, Lurie SF, Berlin FS 1984. Is there familial transmission of pedophilia ? J Nerv Ment Dis 172: 546-548.
24. Garcia-Falgueras A., Swaab DF 2008. A sex difference in the hypothalamic uncinate nucleus: relationship to gender identity. Brain 131: 3132-3146.
25. Goldstein JM, Jerram M., Abbs B., Whitfield-Gabrieli S., Makris N. 2010. Sex differences in stress response circuitry activation dependent on female hormonal cycle. J Neurosci 30: 431-438.
26. Goldstein JM, Seidman LJ, Horton NJ, Makris N., Kennedy DN, Caviness VS Jr, and others. 2001. Normal sexual dimorphism of the adult human brain assessed by in vivo magnetic resonance imaging. Cereb Cortex 11: 490-497.
27. Goldstein JM, Seidman LJ, Oĝ€Brien LM, Horton NJ, Kennedy DN, Makris N., and others. 2002. Impact of normal sexual dimorphisms on sex differences in structural brain abnormalities in schizophrenia assessed by magnetic resonance imaging. Arch Gen Psychiatry 59: 154-164.
28. Gomez-Gil E., Esteva I., Carrasco R., Almaraz MC, Pasaro E., Salamero M., and others. 2010. Birth order and ratio of brothers to sisters in Spanish transsexuals. Arch Sex Behav. 2010 Mar 16. [Epub ahead of print]
29. Good CD, Johnsrude I., Ashburner J., Henson RN, Friston KJ, Frackowiak RS 2001. Cerebral asymmetry and the effects of sex and handedness on brain structure: a voxel-based morphometric analysis of 465 normal adult human brains. Neuroimage 14: 685-700.
30. Goodwin RD, Gotlib IH 2004. Gender differences in depression: the role of personality factors. Psychiatry Res 126: 135-142.
31. Hamer DH, Hu S., Magnuson VL, Hu N., Pattatucci AM 1993. A linkage between DNA markers on the X chromosome and male sexual orientation. Science 261: 321-327.
32. Hebert LE, Scherr PA, McCann JJ, Beckett LA, Evans DA 2001. Is the risk of developing Alzheimerĝ€™s disease greater for women than for men ? Am J Epidemiol 153: 132-136.
33. Hess NH, Hagen EH 2006. Sex differences in indirect aggression: psychological evidence from young adults. Evol Hum Behav 27: 231-245.
34. Hofman MA, Swaab DF 1989. The sexually dimorphic nucleus of the preoptic area in the human brain: a comparative morphometric study. J Anat 164: 55-72.
35. Iijima M., Arisaka O., Minamoto F., Arai Y. 2001. Sex differences in childrenĝ€s free drawings: a study on girls with congenital adrenal hyperplasia. Horm Behav 40: 99-104.
36. Kinnunen LH, Moltz H., Metz J., Cooper M. 2004. Differential brain activation in exclusively homosexual and heterosexual men produced by the selective serotonin reuptake inhibitor, fluoxetine. Brain Res 1024: 251-254.
37. Kovacs KJ, Miklos IH, Bali B. 2004. GABAergic mechanisms constraining the activity of the hypothalamo-pituitary-adrenocortical axis. Ann N Y Acad Sci 1018: 466-476.
38. Kruijver FP, Zhou JN, Pool CW, Hofman MA, Gooren LJ, Swaab DF 2000. Male-to-female transsexuals have female neuron numbers in a limbic nucleus. J Clin Endocrinol Metab 85: 2034-2041.
39. Letenneur L., Launer LJ, Andersen K., Dewey ME, Ott A., Copeland JR, and others. 2000. Education and the risk for Alzheimerĝ€s disease: sex makes a difference. EURODEM pooled analyses. EURODEM Incidence Research Group. Am J Epidemiol 151: 1064-1071.
40. LeVay S. 1991. A difference in hypothalamic structure between heterosexual and homosexual men. Science 253: 1034-1037.
41. Mathews GA, Fane BA, Conway GS, Brook CG, Hines M. 2009. Personality and congenital adrenal hyperplasia: possible effects of prenatal androgen exposure. Horm Behav 55: 285-291.
42. Mazur A., Booth A. 1998. Testosterone and dominance in men. Behav Brain Sci 21: 353-363 ; discussion 363-397.
43. Meyer-Bahlburg HF 2005. Gender identity outcome in female-raised 46,XY persons with penile agenesis, cloacal exstrophy of the bladder, or penile ablation. Arch Sex Behav 34: 423-438.
44. Money J., Erhardt AA 1972. Man and woman, boy and girl: the differentiation and dimorphism of gender identity from conception to maturity. Baltimore: Johns Hopkins University Press.
45. Mustanski BS, Dupree MG, Nievergelt CM, Bocklandt S., Schork NJ, Hamer DH 2005. A genomewide scan of male sexual orientation. Hum Genet 116: 272-278.
46. Nordenstrom A., Servin A., Bohlin G., Larsson A., Wedell A. 2002. Sex-typed toy play behavior correlates with the degree of prenatal androgen exposure assessed by CYP21 genotype in girls with congenital adrenal hyperplasia. J Clin Endocrinol Metab 87: 5119-5124.
47. Paus T., Otaky N., Caramanos Z., MacDonald D., Zijdenbos A., Dĝ€Avirro D., and others. 1996. In vivo morphometry of the intrasulcal gray matter in the human cingulate, paracingulate, and superior-rostral sulci: hemispheric asymmetries, gender differences and probability maps. J Comp Neurol 376: 664-673.
48. Pujol J., Lopez A., Deus J., Cardoner N., Vallejo J., Capdevila A., and others. 2002. Anatomical variability of the anterior cingulate gyrus and basic dimensions of human personality. Neuroimage 15: 847-855.
49. Reiner WG, Gearhart JP 2004. Discordant sexual identity in some genetic males with cloacal exstrophy assigned to female sex at birth. N Engl J Med 350: 333-341.
50. Roca CA, Schmidt PJ, Deuster PA, Danaceau MA, Altemus M., Putnam K., and others. 2005. Sex-related differences in stimulated hypothalamic-pituitary- adrenal axis during induced gonadal suppression. J Clin Endocrinol Metab 90: 4224-4231.
51. Salehi A., Ocampo M., Verhaagen J., Swaab DF 2000. P75 neurotrophin receptor in the nucleus basalis of Meynert in relation to age, sex, and Alzheimerĝ€s disease. Exp Neurol 161: 245-258.
52. Savic I., Lindstrom P. 2008. PET and MRI show differences in cerebral asymmetry and functional connectivity between homo- and heterosexual subjects. Proc Natl Acad Sci U S A 105: 9403-9408.
53. Schiffer B., Krueger T., Paul T., de Greiff A., Forsting M., Leygraf N., and others. 2008 a. Brain response to visual sexual stimuli in homosexual pedophiles. J Psychiatry Neurosci 33: 23-33. (Pubitemid 351252493)
54. Schiffer B., Paul T., Gizewski E., Forsting M., Leygraf N., Schedlowski M., and others. 2008 b. Functional brain correlates of heterosexual paedophilia. Neuroimage 41: 80-91.
55. Schiffer B., Peschel T., Paul T., Gizewski E., Forsting M., Leygraf N., and others. 2007. Structural brain abnormalities in the frontostriatal system and cerebellum in pedophilia. J Psychiatr Res 41: 753-762.
56. Schiltz K., Witzel J., Northoff G., Zierhut K., Gubka U., Fellmann H., and others. 2007. Brain pathology in pedophilic offenders: evidence of volume reduction in the right amygdala and related diencephalic structures. Arch Gen Psychiatry 64: 737-746.
57. Selye H. 1975. Confusion and controversy in the stress field. J Human Stress 1: 37-44.
58. Spratt D. 2000. Sex differences in the brain. J Neuroendocrinol 12: 597-598.
59. Swaab DF 2003. The human hypothalamus. Basic and clinical aspects. Part I: Nuclei of the hypothalamus. In: Aminoff MJ, Boller F, Swaab DF, editors. Handbook of clinical neurology. Amsterdam: Elsevier.
60. Swaab DF 2004. The human hypothalamus. Basic and clinical aspects. Part II: Neuropathology of the hypothalamus and adjacent brain structures. In: Aminoff MJ, Boller F, Swaab DF, editors. Handbook of clinical neurology. Amsterdam: Elsevier.
61. Swaab DF 2008. Sexual orientation and its basis in brain structure and function. Proc Natl Acad Sci U S A 105: 10273-10274.
62. Swaab DF, Fliers E. 1985. A sexually dimorphic nucleus in the human brain. Science 228: 1112-1115.
63. Swaab DF, Garcia-Falgueras A. 2009. Sexual differentiation of the human brain in relation to gender identity and sexual orientation. Funct Neurol 24: 17-28.
64. Swaab DF, Hofman MA 1984. Sexual differentiation of the human brain. A historical perspective. Prog Brain Res 61: 361-374.
65. Taylor SE, Klein LC, Lewis BP, Gruenewald TL, Gurung RA, Updegraff JA 2000. Biobehavioral responses to stress in females: tend-and-befriend, not fight-or-flight. Psychol Rev 107: 411-429.
66. Ter Horst GJ, Wichmann R., Gerrits M., Westenbroek C., Lin Y. 2009. Sex differences in stress responses: focus on ovarian hormones. Physiol Behav 97: 239-249.
67. Wallien MS, Cohen-Kettenis PT 2008. Psychosexual outcome of gender-dysphoric children. J Am Acad Child Adolesc Psychiatry 47: 1413-1423.
68. Wang SS, Kamphuis W., Huitinga I., Zhou JN, Swaab DF 2008. Gene expression analysis in the human hypothalamus in depression by laser microdissection and real-time PCR: the presence of multiple receptor imbalances. Mol Psychiatry 13: 741, 786-799.
69. Zhou JN, Hofman MA, Gooren LJ, Swaab DF 1995. A sex difference in the human brain and its relation to transsexuality. Nature 378: 68-70.
70. Zubenko GS, Stiffler JS, Hughes HB, Hurtt MR, Kaplan BB 1998. Initial results of a genome survey for novel Alzheimerĝ€s disease risk genes: association with a locus on the X chromosome. Am J Med Genet 81: 196-205.