Skip to main content

Advertisement

SpringerLink
Log in

Sex steroids and schizophrenia

  • Published:
Reviews in Endocrine and Metabolic Disorders Aims and scope Submit manuscript

Abstract

The peak in incidence for schizophrenia is during late adolescence for both sexes, but within this time frame the peak is both earlier and steeper for males. Additionally, women have a second peak in incidence following menopause. Two meta-analyses have reported that men have an overall ∼40% greater chance of developing schizophrenia than do women (Aleman et al., 2003; McGrath et al., 2004). These and other findings have led to the suggestion that ovarian hormones may be protective against schizophrenia. Less explored is the potential role of testosterone in schizophrenia, although disruptions in steroid levels have also been reported in men with the illness. The relationship between increased gonadal hormone release per se and peri-adolescent vulnerability for psychiatric illness is difficult to tease apart from other potentially contributory factors in clinical studies, as adolescence is a turbulent period characterized by many social and biological changes. Despite the obvious opportunity provided by animal research, surprisingly little basic science effort has been devoted to this important issue. On the other hand, the animal work offers an understanding of the many ways in which gonadal steroids exert a powerful impact on the brain, both shaping its development and modifying its function during adulthood. Recently, investigators using preclinical models have described a greater male vulnerability to neurodevelopmental insults that are associated with schizophrenia; such studies may provide clinically relevant insights into the role of gonadal steroids in psychiatric illness.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Seeman MV. Psychopathology in women and men: focus on female hormones. Am J Psychiatry. 1997;154(12):1641–7.

    PubMed  CAS  Google Scholar 

  2. Buchanan RW, Carpenter WT. Domains of psychopathology: an approach to the reduction of heterogeneity in schizophrenia. J Nerv Ment Dis. 1994;182(4):193–204.

    Article  PubMed  CAS  Google Scholar 

  3. Saha S, Chant D, Welham J, McGrath J. A systematic review of the prevalence of schizophrenia. PLoS Med. 2005;2(5):e141.

    Article  PubMed  Google Scholar 

  4. Tsuang M. Schizophrenia: genes and environment. Biol Psychiatry. 2000;47(3):210–20.

    Article  PubMed  CAS  Google Scholar 

  5. van Os J, Rutten BP, Poulton R. Gene-environment interactions in schizophrenia: review of epidemiological findings and future directions. Schizophr Bull. 2008;34(6):1066–82.

    Article  PubMed  Google Scholar 

  6. Marenco S, Weinberger DR. The neurodevelopmental hypothesis of schizophrenia: following a trail of evidence from cradle to grave. Dev Psychopathol. 2000;12(3):501–27.

    Article  PubMed  CAS  Google Scholar 

  7. Kraepelin E. Psychiatrie. Leipzig: Barth; 1909.

    Google Scholar 

  8. Angermeyer MC, Kuhn L. Gender differences in age at onset of schizophrenia. An overview. Eur Arch Psychiatry Neurol Sci. 1988;237(6):351–64.

    Article  PubMed  CAS  Google Scholar 

  9. Hafner H, Riecher A, Maurer K, Loffler W, Munk-Jorgensen P, Stromgren E. How does gender influence age at first hospitalization for schizophrenia? A transnational case register study. Psychol Med. 1989;19(4):903–18.

    Article  PubMed  CAS  Google Scholar 

  10. Hafner H, Behrens S, De Vry J, Gattaz WF. Oestradiol enhances the vulnerability threshold for schizophrenia in women by an early effect on dopaminergic neurotransmission. Evidence from an epidemiological study and from animal experiments. Eur Arch Psychiatry Clin Neurosci. 1991;241(1):65–8.

    Article  PubMed  CAS  Google Scholar 

  11. Hambrecht M, Maurer K, Hafner H. Gender differences in schizophrenia in three cultures. Results of the who collaborative study on psychiatric disability. Soc Psychiatry Psychiatr Epidemiol. 1992;27(3):117–21.

    PubMed  CAS  Google Scholar 

  12. Hafner H, Riecher-Rossler A, Maurer K, Fatkenheuer B, Loffler W. First onset and early symptomatology of schizophrenia. A chapter of epidemiological and neurobiological research into age and sex differences. Eur Arch Psychiatry Clin Neurosci. 1992;242(2–3):109–18.

    Article  PubMed  CAS  Google Scholar 

  13. Hafner H, an der Heiden W, Behrens S, Gattaz WF, Hambrecht M, Loffler W, et al. Causes and consequences of the gender difference in age at onset of schizophrenia. Schizophr Bull. 1998;24(1):99–113.

    Article  PubMed  CAS  Google Scholar 

  14. Hafner H, Riecher-Rossler A, An Der Heiden W, Maurer K, Fatkenheuer B, Loffler W. Generating and testing a causal explanation of the gender difference in age at first onset of schizophrenia. Psychol Med. 1993;23(4):925–40.

    Article  PubMed  CAS  Google Scholar 

  15. Hafner H, Maurer K, Loffler W, Riecher-Rossler A. The influence of age and sex on the onset and early course of schizophrenia. Br J Psychiatry. 1993;162:80–6.

    Article  PubMed  CAS  Google Scholar 

  16. Munk-Jorgensen P. First-admission rates and marital status of schizophrenics. Acta Psychiatr Scand. 1987;76(2):210–6.

    Article  PubMed  CAS  Google Scholar 

  17. Konnecke R, Hafner H, Maurer K, Loffler W, an der Heiden W. Main risk factors for schizophrenia: Increased familial loading and pre- and peri-natal complications antagonize the protective effect of oestrogen in women. Schizophr Res. 2000;44(1):81–93.

    Article  PubMed  CAS  Google Scholar 

  18. Albus M, Maier W. Lack of gender differences in age at onset in familial schizophrenia. Schizophr Res. 1995;18(1):51–7.

    Article  PubMed  CAS  Google Scholar 

  19. Cohen RZ, Seeman MV, Gotowiec A, Kopala L. Earlier puberty as a predictor of later onset of schizophrenia in women. Am J Psychiatry. 1999;156(7):1059–64.

    PubMed  CAS  Google Scholar 

  20. Castle DJ, Phelan M, Wessely S, Murray RM. Which patients with non-affective functional psychosis are not admitted at first psychiatric contact? Br J Psychiatry. 1994;165(1):101–6.

    Article  PubMed  CAS  Google Scholar 

  21. Schwartz JE, Fennig S, Tanenberg-Karant M, Carlson G, Craig T, Galambos N, et al. Congruence of diagnoses 2 years after a first-admission diagnosis of psychosis. Arch Gen Psychiatry. 2000;57(6):593–600.

    Article  PubMed  CAS  Google Scholar 

  22. Aleman A, Kahn RS, Selten JP. Sex differences in the risk of schizophrenia: evidence from meta-analysis. Arch Gen Psychiatry. 2003;60(6):565–71.

    Article  PubMed  Google Scholar 

  23. McGrath J, Saha S, Welham J, El Saadi O, MacCauley C, Chant D. A systematic review of the incidence of schizophrenia: the distribution of rates and the influence of sex, urbanicity, migrant status and methodology. BMC Med. 2004;2:13.

    Article  PubMed  Google Scholar 

  24. Hafner H, Maurer K, Loffler W, Fatkenheuer B, an der Heiden W, Riecher-Rossler A, et al. The epidemiology of early schizophrenia. Influence of age and gender on onset and early course. Br J Psychiatry. 1994;23:29–38.

    Google Scholar 

  25. Hafner H, Maurer K, Loffler W, an der Heiden W, Munk-Jorgensen P, Hambrecht M, et al. The abc schizophrenia study: a preliminary overview of the results. Soc Psychiatry Psychiatr Epidemiol. 1998;33(8):380–6.

    Article  PubMed  CAS  Google Scholar 

  26. Zigler E, Glick M, Marsh A. Premorbid social competence and outcome among schizophrenic and nonschizophrenic patients. J Nerv Ment Dis. 1979;167(8):478–83.

    Article  PubMed  CAS  Google Scholar 

  27. Larsen TK, McGlashan TH, Johannessen JO, Vibe-Hansen L. First-episode schizophrenia: Ii. Premorbid patterns by gender. Schizophr Bull. 1996;22(2):257–69.

    Article  PubMed  CAS  Google Scholar 

  28. Angermeyer MC, Goldstein JM, Kuehn L. Gender differences in schizophrenia: rehospitalization and community survival. Psychol Med. 1989;19(2):365–82.

    Article  PubMed  CAS  Google Scholar 

  29. Shepherd M, Watt D, Falloon I, Smeeton N. The natural history of schizophrenia: A five-year follow-up study of outcome and prediction in a representative sample of schizophrenics. Psychol Med Monogr Suppl. 1989;15:1–46.

    Article  PubMed  CAS  Google Scholar 

  30. Salokangas RK. Prognostic implications of the sex of schizophrenic patients. Br J Psychiatry. 1983;142:145–51.

    Article  PubMed  CAS  Google Scholar 

  31. Seeman MV. Current outcome in schizophrenia: women vs men. Acta Psychiatr Scand. 1986;73(6):609–17.

    Article  PubMed  CAS  Google Scholar 

  32. Grossman LS, Harrow M, Rosen C, Faull R, Strauss GP. Sex differences in schizophrenia and other psychotic disorders: a 20-year longitudinal study of psychosis and recovery. Compr Psychiatry. 2008;49(6):523–9.

    Article  PubMed  Google Scholar 

  33. Shtasel DL, Gur RE, Gallacher F, Heimberg C, Gur RC. Gender differences in the clinical expression of schizophrenia. Schizophr Res. 1992;7(3):225–31.

    Article  PubMed  CAS  Google Scholar 

  34. Gur RE, Petty RG, Turetsky BI, Gur RC. Schizophrenia throughout life: sex differences in severity and profile of symptoms. Schizophr Res. 1996;21(1):1–12.

    Article  PubMed  CAS  Google Scholar 

  35. Meltzer HY, Busch DA, Fang VS. Serum neuroleptic and prolactin levels in schizophrenic patients and clinical response. Psychiatry Res. 1983;9(4):271–83.

    Article  PubMed  CAS  Google Scholar 

  36. Bowers Jr MB, Swigar ME, Jatlow PI, Goicoechea N. Plasma catecholamine metabolites and early response to haloperidol. J Clin Psychiatry. 1984;45(6):248–51.

    PubMed  Google Scholar 

  37. Melkersson KI, Hulting AL, Rane AJ. Dose requirement and prolactin elevation of antipsychotics in male and female patients with schizophrenia or related psychoses. Br J Clin Pharmacol. 2001;51(4):317–24.

    Article  PubMed  CAS  Google Scholar 

  38. Carrillo JA, Benitez J. Cyp1a2 activity, gender and smoking, as variables influencing the toxicity of caffeine. Br J Clin Pharmacol. 1996;41(6):605–8.

    Article  PubMed  CAS  Google Scholar 

  39. Kelly DL, Conley RR, Tamminga CA. Differential olanzapine plasma concentrations by sex in a fixed-dose study. Schizophr Res. 1999;40(2):101–4.

    Article  PubMed  CAS  Google Scholar 

  40. Tanaka E. Gender-related differences in pharmacokinetics and their clinical significance. J Clin Pharm Ther. 1999;24(5):339–46.

    Article  PubMed  CAS  Google Scholar 

  41. DeLisi LE. The significance of age of onset for schizophrenia. Schizophr Bull. 1992;18(2):209–15.

    PubMed  CAS  Google Scholar 

  42. Andia AM, Zisook S, Heaton RK, Hesselink J, Jernigan T, Kuck J, et al. Gender differences in schizophrenia. J Nerv Ment Dis. 1995;183(8):522–8.

    Article  PubMed  CAS  Google Scholar 

  43. Grossman LS, Harrow M, Rosen C, Faull R. Sex differences in outcome and recovery for schizophrenia and other psychotic and nonpsychotic disorders. Psychiatric Services (Washington, DC). 2006;57(6):844–50.

    Article  Google Scholar 

  44. Bottlender R, Jager M, Groll C, Strauss A, Moller HJ. Deficit states in schizophrenia and their association with the length of illness and gender. Eur Arch Psychiatry Clin Neurosci. 2001;251(6):272–8.

    Article  PubMed  CAS  Google Scholar 

  45. Goldstein JM, Link BG. Gender and the expression of schizophrenia. J Psychiatr Res. 1988;22(2):141–55.

    Article  PubMed  CAS  Google Scholar 

  46. Willhite RK, Niendam TA, Bearden CE, Zinberg J, O’Brien MP, Cannon TD. Gender differences in symptoms, functioning and social support in patients at ultra-high risk for developing a psychotic disorder. Schizophr Res. 2008;104(1–3):237–45.

    Article  PubMed  Google Scholar 

  47. McGlashan TH, Bardenstein KK. Gender differences in affective, schizoaffective, and schizophrenic disorders. Schizophr Bull. 1990;16(2):319–29.

    PubMed  CAS  Google Scholar 

  48. Seidman LJ, Goldstein JM, Goodman JM, Koren D, Turner WM, Faraone SV, et al. Sex differences in olfactory identification and wisconsin card sorting performance in schizophrenia: Relationship to attention and verbal ability. Biol Psychiatry. 1997;42(2):104–15.

    Article  PubMed  CAS  Google Scholar 

  49. Goldstein JM, Seidman LJ, Goodman JM, Koren D, Lee H, Weintraub S, et al. Are there sex differences in neuropsychological functions among patients with schizophrenia? Am J Psychiatry. 1998;155(10):1358–64.

    PubMed  CAS  Google Scholar 

  50. Walder DJ, Seidman LJ, Cullen N, Su J, Tsuang MT, Goldstein JM. Sex differences in language dysfunction in schizophrenia. Am J Psychiatry. 2006;163(3):470–7.

    Article  PubMed  Google Scholar 

  51. Nopoulos P, Flaum M, Andreasen NC. Sex differences in brain morphology in schizophrenia. Am J Psychiatry. 1997;154(12):1648–54.

    PubMed  CAS  Google Scholar 

  52. Andreasen NC, Swayze 2nd VW, Flaum M, Yates WR, Arndt S, McChesney C. Ventricular enlargement in schizophrenia evaluated with computed tomographic scanning. Effects of gender, age, and stage of illness. Arch Gen Psychiatry. 1990;47(11):1008–15.

    Article  PubMed  CAS  Google Scholar 

  53. Goldberg TE, Gold JM, Torrey EF, Weinberger DR. Lack of sex differences in the neuropsychological performance of patients with schizophrenia. Am J Psychiatry. 1995;152(6):883–8.

    PubMed  CAS  Google Scholar 

  54. Hoff AL, Wieneke M, Faustman WO, Horon R, Sakuma M, Blankfeld H, et al. Sex differences in neuropsychological functioning of first-episode and chronically ill schizophrenic patients. Am J Psychiatry. 1998;155(10):1437–9.

    PubMed  CAS  Google Scholar 

  55. Gur RE, Mozley PD, Shtasel DL, Cannon TD, Gallacher F, Turetsky B, et al. Clinical subtypes of schizophrenia: differences in brain and csf volume. Am J Psychiatry. 1994;151(3):343–50.

    PubMed  CAS  Google Scholar 

  56. Lewine RR, Walker EF, Shurett R, Caudle J, Haden C. Sex differences in neuropsychological functioning among schizophrenic patients. Am J Psychiatry. 1996;153(9):1178–84.

    PubMed  CAS  Google Scholar 

  57. Walker EF, Lewine RR. Sampling biases in studies of gender and schizophrenia. Schizophr Bull. 1993;19(1):1–7. discussion 9–14.

    PubMed  CAS  Google Scholar 

  58. Goldstein JM. Sampling biases in studies of gender and schizophrenia: a reply. Schizophr Bull. 1993;19(1):9–14.

    Google Scholar 

  59. Kendell RE, Chalmers JC, Platz C. Epidemiology of puerperal psychoses. Br J Psychiatry. 1987;150:662–73.

    Article  PubMed  CAS  Google Scholar 

  60. Mahe V, Dumaine A. Oestrogen withdrawal associated psychoses. Acta Psychiatr Scand. 2001;104(5):323–31.

    Article  PubMed  CAS  Google Scholar 

  61. Bergemann N, Parzer P, Nagl I, Salbach B, Runnebaum B, Mundt C, et al. Acute psychiatric admission and menstrual cycle phase in women with schizophrenia. Arch Wom Ment Health. 2002;5(3):119–26.

    Article  CAS  Google Scholar 

  62. Hallonquist JD, Seeman MV, Lang M, Rector NA. Variation in symptom severity over the menstrual cycle of schizophrenics. Biol Psychiatry. 1993;33(3):207–9.

    Article  PubMed  CAS  Google Scholar 

  63. Riecher-Rossler A, Hafner H, Stumbaum M, Maurer K, Schmidt R. Can estradiol modulate schizophrenic symptomatology? Schizophr Bull. 1994;20(1):203–14.

    PubMed  CAS  Google Scholar 

  64. Rubin LH, Carter CS, Drogos L, Pournajafi-Nazarloo H, Sweeney JA, Maki PM. Peripheral oxytocin is associated with reduced symptom severity in schizophrenia. Schizophr Res. 2010;124(1–3):13–21.

    Article  PubMed  Google Scholar 

  65. Bergemann N, Parzer P, Runnebaum B, Resch F, Mundt C. Estrogen, menstrual cycle phases, and psychopathology in women suffering from schizophrenia. Psychol Med. 2007;37(10):1427–36.

    Article  PubMed  Google Scholar 

  66. Gattaz WF, Vogel P, Riecher-Rossler A, Soddu G. Influence of the menstrual cycle phase on the therapeutic response in schizophrenia. Biol Psychiatry. 1994;36(2):137–9.

    Article  PubMed  CAS  Google Scholar 

  67. Hoff AL, Kremen WS, Wieneke MH, Lauriello J, Blankfeld HM, Faustman WO, et al. Association of estrogen levels with neuropsychological performance in women with schizophrenia. Am J Psychiatry. 2001;158(7):1134–9.

    Article  PubMed  CAS  Google Scholar 

  68. Ko YH, Joe SH, Cho W, Park JH, Lee JJ, Jung IK, et al. Estrogen, cognitive function and negative symptoms in female schizophrenia. Neuropsychobiology. 2006;53(4):169–75.

    Article  PubMed  CAS  Google Scholar 

  69. Halari R, Kumari V, Mehrotra R, Wheeler M, Hines M, Sharma T. The relationship of sex hormones and cortisol with cognitive functioning in schizophrenia. J Psychopharmacology Oxf Engl. 2004;18(3):366–74.

    Article  CAS  Google Scholar 

  70. Felthous AR, Robinson DB, Conroy RW. Prevention of recurrent menstrual psychosis by an oral contraceptive. Am J Psychiatry. 1980;137(2):245–6.

    PubMed  CAS  Google Scholar 

  71. Tunde-Ayinmode M, Singh AK, Marsden K. Improved functioning in a women with schizophrenia on exclusive therapy with oestrogen pills. Australas Psychiatry. 2008;10(4):403–4.

    Article  Google Scholar 

  72. Lindamer LA, Lohr JB, Harris MJ, Jeste DV. Gender, estrogen, and schizophrenia. Psychopharmacol Bull. 1997;33(2):221–8.

    PubMed  CAS  Google Scholar 

  73. Nordstrom AL, Olsson H, Halldin C. A pet study of d2 dopamine receptor density at different phases of the menstrual cycle. Psychiatry Res. 1998;83(1):1–6.

    Article  PubMed  CAS  Google Scholar 

  74. Di Paolo T. Modulation of brain dopamine transmission by sex steroids. Rev Neurosci. 1994;5(1):27–41.

    Article  PubMed  Google Scholar 

  75. Nordstrom AL, Farde L. Plasma prolactin and central d2 receptor occupancy in antipsychotic drug-treated patients. J Clin Psychopharmacol. 1998;18(4):305–10.

    Article  PubMed  CAS  Google Scholar 

  76. Crawford AM, Beasley Jr CM, Tollefson GD. The acute and long-term effect of olanzapine compared with placebo and haloperidol on serum prolactin concentrations. Schizophr Res. 1997;26(1):41–54.

    Article  PubMed  CAS  Google Scholar 

  77. Hamner MB, Arvanitis LA, Miller BG, Link CG, Hong WW. Plasma prolactin in schizophrenia subjects treated with seroquel (ici 204,636). Psychopharmacol Bull. 1996;32(1):107–10.

    PubMed  CAS  Google Scholar 

  78. Bergemann N, Mundt C, Parzer P, Jannakos I, Nagl I, Salbach B, et al. Plasma concentrations of estradiol in women suffering from schizophrenia treated with conventional versus atypical antipsychotics. Schizophr Res. 2005;73(2–3):357–66.

    Article  PubMed  Google Scholar 

  79. Maric N, Popovic V, Jasovic-Gasic M, Pilipovic N, van Os J. Cumulative exposure to estrogen and psychosis: a peak bone mass, case-control study in first-episode psychosis. Schizophr Res. 2005;73(2–3):351–5.

    Article  PubMed  Google Scholar 

  80. Perlman WR, Webster MJ, Kleinman JE, Weickert CS. Reduced glucocorticoid and estrogen receptor alpha messenger ribonucleic acid levels in the amygdala of patients with major mental illness. Biol Psychiatry. 2004;56(11):844–52.

    Article  PubMed  CAS  Google Scholar 

  81. Perlman WR, Matsumoto M, Beltaifa S, Hyde TM, Saunders RC, Webster MJ, et al. Expression of estrogen receptor alpha exon-deleted mrna variants in the human and non-human primate frontal cortex. Neuroscience. 2005;134(1):81–95.

    Article  PubMed  CAS  Google Scholar 

  82. Perlman WR, Tomaskovic-Crook E, Montague DM, Webster MJ, Rubinow DR, Kleinman JE, et al. Alteration in estrogen receptor alpha mrna levels in frontal cortex and hippocampus of patients with major mental illness. Biol Psychiatry. 2005;58(10):812–24.

    Article  PubMed  CAS  Google Scholar 

  83. Weickert CS, Miranda-Angulo AL, Wong J, Perlman WR, Ward SE, Radhakrishna V, et al. Variants in the estrogen receptor alpha gene and its mrna contribute to risk for schizophrenia. Hum Mol Genet. 2008;17(15):2293–309.

    Article  PubMed  CAS  Google Scholar 

  84. Kulkarni J, de Castella A, Smith D, Taffe J, Keks N, Copolov D. A clinical trial of the effects of estrogen in acutely psychotic women. Schizophr Res. 1996;20(3):247–52.

    Article  PubMed  CAS  Google Scholar 

  85. Kulkarni J, Riedel A, de Castella AR, Fitzgerald PB, Rolfe TJ, Taffe J, et al. Estrogen - a potential treatment for schizophrenia. Schizophr Res. 2001;48(1):137–44.

    Article  PubMed  CAS  Google Scholar 

  86. Kulkarni J, Riedel A, de Castella AR, Fitzgerald PB, Rolfe TJ, Taffe J, et al. A clinical trial of adjunctive oestrogen treatment in women with schizophrenia. Arch Wom Ment Health. 2002;5(3):99–104.

    Article  CAS  Google Scholar 

  87. Kulkarni J, de Castella A, Fitzgerald PB, Gurvich CT, Bailey M, Bartholomeusz C, et al. Estrogen in severe mental illness: a potential new treatment approach. Arch Gen Psychiatry. 2008;65(8):955–60.

    Article  PubMed  Google Scholar 

  88. Akhondzadeh S, Nejatisafa AA, Amini H, Mohammadi MR, Larijani B, Kashani L, et al. Adjunctive estrogen treatment in women with chronic schizophrenia: a double-blind, randomized, and placebo-controlled trial. Progr Neuro Psychopharmacol Biol Psychiatr. 2003;27(6):1007–12.

    Article  CAS  Google Scholar 

  89. Louza MR, Marques AP, Elkis H, Bassitt D, Diegoli M, Gattaz WF. Conjugated estrogens as adjuvant therapy in the treatment of acute schizophrenia: a double-blind study. Schizophr Res. 2004;66(2–3):97–100.

    Article  PubMed  Google Scholar 

  90. Bergemann N, Mundt C, Parzer P, Pakrasi M, Eckstein-Mannsperger U, Haisch S, et al. 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. 2005;74(2–3):125–34.

    Article  PubMed  Google Scholar 

  91. Bergemann N, Parzer P, Jaggy S, Auler B, Mundt C, Maier-Braunleder S. Estrogen and comprehension of metaphoric speech in women suffering from schizophrenia: results of a double-blind, placebo-controlled trial. Schizophr Bull. 2008;34(6):1172–81.

    Article  PubMed  Google Scholar 

  92. Lindamer LA, Buse DC, Lohr JB, Jeste DV. Hormone replacement therapy in postmenopausal women with schizophrenia: positive effect on negative symptoms? Biol Psychiatry. 2001;49(1):47–51.

    Article  PubMed  CAS  Google Scholar 

  93. Kulkarni J, Gurvich C, Lee SJ, Gilbert H, Gavrilidis E, de Castella A, et al. Piloting the effective therapeutic dose of adjunctive selective estrogen receptor modulator treatment in postmenopausal women with schizophrenia. Psychoneuroendocrinology. 2010;35(8):1142–7.

    Article  PubMed  CAS  Google Scholar 

  94. Kulkarni J, de Castella A, Headey B, Marston N, Sinclair K, Lee S, et al. Estrogens and men with schizophrenia: is there a case for adjunctive therapy? Schizophr Res. 2011;125(2–3):278–83.

    Article  PubMed  Google Scholar 

  95. Talih F, Fattal O, Malone Jr D. Anabolic steroid abuse: psychiatric and physical costs. Cleve Clin J Med. 2007;74(5):341–4. 6, 9–52.

    Article  PubMed  Google Scholar 

  96. Rinieris P, Hatzimanolis J, Markianos M, Stefanis C. Effects of 4 weeks treatment with chlorpromazine and/or trihexyphenidyl on the pituitary-gonadal axis in male paranoid schizophrenics. Eur Arch Psychiatry Neurol Sci. 1988;237(4):189–93.

    Article  PubMed  CAS  Google Scholar 

  97. Rinieris P, Hatzimanolis J, Markianos M, Stefanis C. Effects of treatment with various doses of haloperidol on the pituitary-gonadal axis in male schizophrenic patients. Neuropsychobiology. 1989;22(3):146–9.

    Article  PubMed  CAS  Google Scholar 

  98. Kaneda Y, Fujii A. Effects of chronic neuroleptic administration on the hypothalamo-pituitary-gonadal axis of male schizophrenics. Progr Neuro Psychopharmacol Biol Psychiatr. 2000;24(2):251–8.

    Article  CAS  Google Scholar 

  99. Brambilla F, Guerrini A, Riggi F, Ricciardi F. Psychoendocrine investigation in schizophrenia: relationship between pituitary-gonadal function and behavior. Dis Nerv Syst. 1974;35(8):362–7.

    PubMed  CAS  Google Scholar 

  100. Brambilla F, Guerrini A, Guastalla A, Rovere C, Riggi F. Neuroendocrine effects of haloperidol therapy in chronic schizophrenia. Psychopharmacologia. 1975;44(1):17–22.

    Article  PubMed  CAS  Google Scholar 

  101. Brooksbank BW, MacSweeney DA, Johnson AL, Cunningham AE, Wilson DA, Coppen A. Androgen excretion and physique in schizophrenia. Br J Psychiatry. 1970;117(539):413–20.

    Article  PubMed  CAS  Google Scholar 

  102. Tourney G, Erb JL. Temporal variations in androgens and stress hormones in control and schizophrenic subjects. Biol Psychiatry. 1979;14(2):395–404.

    PubMed  CAS  Google Scholar 

  103. Tourney G, Hatfield L. Plasma androgens in male schizophrenics. Arch Gen Psychiatry. 1972;27(6):753–5.

    Article  PubMed  CAS  Google Scholar 

  104. Ferrier IN, Cotes PM, Crow TJ, Johnstone EC. Gonadotropin secretion abnormalities in chronic schizophrenia. Psychol Med. 1982;12(2):263–73.

    Article  PubMed  CAS  Google Scholar 

  105. Cantalamessa L, Catania A, Silva A, Orsatti A, Baldini M, Mosca G, et al. Gonadotropin response to gonadotropin releasing hormone in acute schizophrenia. Progr Neuro Psychopharmacol Biol Psychiatr. 1984;8(3):411–7.

    CAS  Google Scholar 

  106. Oades RD, Schepker R. Serum gonadal steroid hormones in young schizophrenic patients. Psychoneuroendocrinology. 1994;19(4):373–85.

    Article  PubMed  CAS  Google Scholar 

  107. Brown AS, Hembree WC, Friedman JH, Kaufmann CA, Gorman JM. The gonadal axis in men with schizophrenia. Psychiatry Res. 1995;57(3):231–9.

    Article  PubMed  CAS  Google Scholar 

  108. Ritsner M, Gibel A, Ram E, Maayan R, Weizman A. Alterations in dhea metabolism in schizophrenia: two-month case-control study. Eur Neuropsychopharmacol. 2006;16(2):137–46.

    Article  PubMed  CAS  Google Scholar 

  109. Harris DS, Wolkowitz OM, Reus VI. Movement disorder, memory, psychiatric symptoms and serum dhea levels in schizophrenic and schizoaffective patients. World J Biol Psychiatry. 2001;2(2):99–102.

    Article  PubMed  CAS  Google Scholar 

  110. Brophy MH, Rush AJ, Crowley G. Cortisol, estradiol, and androgens in acutely ill paranoid schizophrenics. Biol Psychiatry. 1983;18(5):583–90.

    PubMed  CAS  Google Scholar 

  111. Ceskova E, Prikryl R, Kasparek T. Testosterone in first-episode schizophrenia. Neuro Endocrinol Lett. 2007;28(6):811–4.

    PubMed  CAS  Google Scholar 

  112. Huber TJ, Tettenborn C, Leifke E, Emrich HM. Sex hormones in psychotic men. Psychoneuroendocrinology. 2005;30(1):111–4.

    Article  PubMed  CAS  Google Scholar 

  113. Taherianfard M, Shariaty M. Evaluation of serum steroid hormones in schizophrenic patients. Indian J Med Sci. 2004;58(1):3–9.

    PubMed  CAS  Google Scholar 

  114. van Rijn S, Aleman A, de Sonneville L, Sprong M, Ziermans T, Schothorst P, et al. Neuroendocrine markers of high risk for psychosis: Salivary testosterone in adolescent boys with prodromal symptoms. Psychol Med. 2011;41(3):499–508.

    Article  PubMed  Google Scholar 

  115. Shirayama Y, Hashimoto K, Suzuki Y, Higuchi T. Correlation of plasma neurosteroid levels to the severity of negative symptoms in male patients with schizophrenia. Schizophr Res. 2002;58(1):69–74.

    Article  PubMed  Google Scholar 

  116. Goyal RO, Sagar R, Ammini AC, Khurana ML, Alias AG. Negative correlation between negative symptoms of schizophrenia and testosterone levels. Ann NY Acad Sci. 2004;1032:291–4.

    Article  PubMed  CAS  Google Scholar 

  117. Akhondzadeh S, Rezaei F, Larijani B, Nejatisafa AA, Kashani L, Abbasi SH. Correlation between testosterone, gonadotropins and prolactin and severity of negative symptoms in male patients with chronic schizophrenia. Schizophr Res. 2006;84(2–3):405–10.

    Article  PubMed  Google Scholar 

  118. Ko YH, Jung SW, Joe SH, Lee CH, Jung HG, Jung IK, et al. Association between serum testosterone levels and the severity of negative symptoms in male patients with chronic schizophrenia. Psychoneuroendocrinology. 2007;32(4):385–91.

    Article  PubMed  CAS  Google Scholar 

  119. Zumoff B, Strain GW, Miller LK, Rosner W, Senie R, Seres DS, et al. Plasma free and non-sex-hormone-binding-globulin-bound testosterone are decreased in obese men in proportion to their degree of obesity. J Clin Endocrinol Metab. 1990;71(4):929–31.

    Article  PubMed  CAS  Google Scholar 

  120. Ko YH, Lew YM, Jung SW, Joe SH, Lee CH, Jung HG, et al. Short-term testosterone augmentation in male schizophrenics: a randomized, double-blind, placebo-controlled trial. J Clin Psychopharmacol. 2008;28(4):375–83.

    Article  PubMed  CAS  Google Scholar 

  121. Strous RD, Maayan R, Lapidus R, Stryjer R, Lustig M, Kotler M, et al. Dehydroepiandrosterone augmentation in the management of negative, depressive, and anxiety symptoms in schizophrenia. Arch Gen Psychiatry. 2003;60(2):133–41.

    Article  PubMed  CAS  Google Scholar 

  122. Strous RD. Dehydroepiandrosterone (dhea) augmentation in the management of schizophrenia symptomatology. Essent Psychopharmacol. 2005;6(3):141–7.

    PubMed  Google Scholar 

  123. Baulieu EE, Robel P. Dehydroepiandrosterone and dehydroepiandrosterone sulfate as neuroactive neurosteroids. J Endocrinol. 1996;150(Suppl):S221–39.

    PubMed  CAS  Google Scholar 

  124. Ritsner MS, Gibel A, Ratner Y, Tsinovoy G, Strous RD. Improvement of sustained attention and visual and movement skills, but not clinical symptoms, after dehydroepiandrosterone augmentation in schizophrenia: a randomized, double-blind, placebo-controlled, crossover trial. J Clin Psychopharmacol. 2006;26(5):495–9.

    Article  PubMed  CAS  Google Scholar 

  125. Nachshoni T, Ebert T, Abramovitch Y, Assael-Amir M, Kotler M, Maayan R, et al. Improvement of extrapyramidal symptoms following dehydroepiandrosterone (dhea) administration in antipsychotic treated schizophrenia patients: a randomized, double-blind placebo controlled trial. Schizophr Res. 2005;79(2–3):251–6.

    Article  PubMed  Google Scholar 

  126. Honekopp J, Bartholdt L, Beier L, Liebert A. Second to fourth digit length ratio (2d:4d) and adult sex hormone levels: new data and a meta-analytic review. Psychoneuroendocrinology. 2007;32(4):313–21.

    Article  PubMed  CAS  Google Scholar 

  127. Collinson SL, Lim M, Chaw JH, Verma S, Sim K, Rapisarda A, et al. Increased ratio of 2nd to 4th digit (2d:4d) in schizophrenia. Psychiatr Res. 176(1):8–12.

  128. Koenig JI, Kirkpatrick B, Lee P. Glucocorticoid hormones and early brain development in schizophrenia. Neuropsychopharmacology. 2002;27(2):309–18.

    Article  PubMed  CAS  Google Scholar 

  129. van Os J, Selten JP. Prenatal exposure to maternal stress and subsequent schizophrenia. The may 1940 invasion of the Netherlands. Br J Psychiatry. 1998;172:324–6.

    Article  PubMed  Google Scholar 

  130. Zarrow MX, Philpott JE, Denenberg VH. Passage of 14c-4-corticosterone from the rat mother to the foetus and neonate. Nature. 1970;226(5250):1058–9.

    Article  PubMed  CAS  Google Scholar 

  131. Clancy B, Darlington RB, Finlay BL. Translating developmental time across mammalian species. Neuroscience. 2001;105(1):7–17.

    Article  PubMed  CAS  Google Scholar 

  132. Kinnunen AK, Koenig JI, Bilbe G. Repeated variable prenatal stress alters pre- and postsynaptic gene expression in the rat frontal pole. J Neurochem. 2003;86(3):736–48.

    Article  PubMed  CAS  Google Scholar 

  133. Koenig JI, Elmer GI, Shepard PD, Lee PR, Mayo C, Joy B, et al. Prenatal exposure to a repeated variable stress paradigm elicits behavioral and neuroendocrinological changes in the adult offspring: potential relevance to schizophrenia. Behav Brain Res. 2005;156(2):251–61.

    Article  PubMed  Google Scholar 

  134. Lee PR, Brady DL, Shapiro RA, Dorsa DM, Koenig JI. Prenatal stress generates deficits in rat social behavior: reversal by oxytocin. Brain Res. 2007;1156:152–67.

    Article  PubMed  CAS  Google Scholar 

  135. Markham JA, Koenig JI. Prefrontal neuronal architecture is disrupted in the rat prenatal stress model of schizophrenia. Schizophr Bull. 2009;35(Supplement 1):137.

    Google Scholar 

  136. Markham JA, Koenig JI. Prenatal stress: role in psychotic and depressive diseases. Psychopharmacology. in press.

  137. Markham JA, Taylor AR, Taylor SB, Bell DB, Koenig JI. Characterization of the cognitive impairments induced by prenatal exposure to stress in the rat. Front Behav Neurosci. 2010;4:Article 173.

  138. Guillin O, Abi-Dargham A, Laruelle M. Neurobiology of dopamine in schizophrenia. Int Rev Neurobiol. 2007;78:1–39.

    Article  PubMed  CAS  Google Scholar 

  139. Creese I, Iversen SD. The pharmacological and anatomical substrates of the amphetamine response in the rat. Brain Res. 1975;83(3):419–36.

    Article  PubMed  CAS  Google Scholar 

  140. Markham JA, Mullins SE, Koenig JI. Peri-adolescent maturation of object recognition memory and associative memory is disrupted in male, but not female, rats exposed to prenatal stress. Society for Neuroscience Abstracts 2009:341.26.

  141. Markham JA, Taylor AR, Shelton S, Brady-Bell D, Koenig JI. The repeated variable prenatal stress paradigm as a rodent model for schizophrenia. Neurobiology of Stress Workshop Abstracts; San Rafael, CA2008.

  142. Steckler T, Drinkenburg WH, Sahgal A, Aggleton JP. Recognition memory in rats–ii. Neuroanatomical substrates. Prog Neurobiol. 1998;54(3):313–32.

    Article  PubMed  CAS  Google Scholar 

  143. Quirk GJ, Russo GK, Barron JL, Lebron K. The role of ventromedial prefrontal cortex in the recovery of extinguished fear. J Neurosci. 2000;20(16):6225–31.

    PubMed  CAS  Google Scholar 

  144. Markham JA, Morris JR, Juraska JM. Neuron number decreases in the rat ventral, but not dorsal, medial prefrontal cortex between adolescence and adulthood. Neuroscience. 2007;144(3):961–8.

    Article  PubMed  CAS  Google Scholar 

  145. Sowell ER, Thompson PM, Holmes CJ, Jernigan TL, Toga AW. In vivo evidence for post-adolescent brain maturation in frontal and striatal regions. Nat Neurosci. 1999;2(10):859–61.

    Article  PubMed  CAS  Google Scholar 

  146. Giedd JN, Blumenthal J, Jeffries NO, Castellanos FX, Liu H, Zijdenbos A, et al. Brain development during childhood and adolescence: a longitudinal mri study. Nat Neurosci. 1999;2(10):861–3.

    Article  PubMed  CAS  Google Scholar 

  147. Brown AS, Susser ES. In utero infection and adult schizophrenia. Ment Retard Dev Disabil Res Rev. 2002;8(1):51–7.

    Article  PubMed  Google Scholar 

  148. Meyer U, Feldon J, Fatemi SH. In-vivo rodent models for the experimental investigation of prenatal immune activation effects in neurodevelopmental brain disorders. Neurosci Biobehav Rev. 2009;33(7):1061–79.

    Article  PubMed  CAS  Google Scholar 

  149. Markham JA. Sex steroids and schizophrenia. Reviews in Endocrine and Metabolic Disorders. accepted in revision.

  150. Fortier ME, Luheshi GN, Boksa P. Effects of prenatal infection on prepulse inhibition in the rat depend on the nature of the infectious agent and the stage of pregnancy. Behav Brain Res. 2007;181(2):270–7.

    Article  PubMed  Google Scholar 

  151. Romero E, Ali C, Molina-Holgado E, Castellano B, Guaza C, Borrell J. Neurobehavioral and immunological consequences of prenatal immune activation in rats. Influence of antipsychotics. Neuropsychopharmacology. 2007;32(8):1791–804.

    Article  PubMed  CAS  Google Scholar 

  152. Borrell J, Vela JM, Arevalo-Martin A, Molina-Holgado E, Guaza C. Prenatal immune challenge disrupts sensorimotor gating in adult rats. Implications for the etiopathogenesis of schizophrenia. Neuropsychopharmacology. 2002;26(2):204–15.

    Article  PubMed  CAS  Google Scholar 

  153. Swerdlow NR, Weber M, Qu Y, Light GA, Braff DL. Realistic expectations of prepulse inhibition in translational models for schizophrenia research. Psychopharmacology. 2008;199(3):331–88.

    Article  PubMed  CAS  Google Scholar 

  154. Powell SB, Zhou X, Geyer MA. Prepulse inhibition and genetic mouse models of schizophrenia. Behav Brain Res. 2009;204(2):282–94.

    Article  PubMed  CAS  Google Scholar 

  155. Braff DL, Geyer MA, Swerdlow NR. Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies. Psychopharmacology. 2001;156(2–3):234–58.

    Article  PubMed  CAS  Google Scholar 

  156. Romero E, Guaza C, Castellano B, Borrell J. Ontogeny of sensorimotor gating and immune impairment induced by prenatal immune challenge in rats: Implications for the etiopathology of schizophrenia. Mol Psychiatr. 2008.

  157. Kumari V, Aasen I, Sharma T. Sex differences in prepulse inhibition deficits in chronic schizophrenia. Schizophr Res. 2004;69(2–3):219–35.

    Article  PubMed  Google Scholar 

  158. Meyer U, Feldon J, Schedlowski M, Yee BK. Towards an immuno-precipitated neurodevelopmental animal model of schizophrenia. Neurosci Biobehav Rev. 2005;29(6):913–47.

    Article  PubMed  CAS  Google Scholar 

  159. Meyer U, Nyffeler M, Schwendener S, Knuesel I, Yee BK, Feldon J. Relative prenatal and postnatal maternal contributions to schizophrenia-related neurochemical dysfunction after in utero immune challenge. Neuropsychopharmacology. 2008;33(2):441–56.

    Article  PubMed  Google Scholar 

  160. Schwendener S, Meyer U, Feldon J. Deficient maternal care resulting from immunological stress during pregnancy is associated with a sex-dependent enhancement of conditioned fear in the offspring. J Neurodevelop Disord. 2009;1:15–32.

    Article  Google Scholar 

  161. Morris JA, Jordan CL, Breedlove SM. Sexual differentiation of the vertebrate nervous system. Nat Neurosci. 2004;7(10):1034–9.

    Article  PubMed  CAS  Google Scholar 

  162. Schulz KM, Molenda-Figueira HA, Sisk CL. Back to the future: the organizational-activational hypothesis adapted to puberty and adolescence. Horm Behav. 2009;55(5):597–604.

    Article  PubMed  CAS  Google Scholar 

  163. Lewis DA, Sweet RA. Schizophrenia from a neural circuitry perspective: advancing toward rational pharmacological therapies. J Clin Investig. 2009;119(4):706–16.

    Article  PubMed  CAS  Google Scholar 

  164. Stander N, Wagner WM, Goddard A, Kirberger RM. Ultrasonographic appearance of canine parvoviral enteritis in puppies. Vet Radiol Ultrasound. 51(1):69–74.

  165. Lenroot RK, Gogtay N, Greenstein DK, Wells EM, Wallace GL, Clasen LS, et al. Sexual dimorphism of brain developmental trajectories during childhood and adolescence. Neuroimage. 2007;36(4):1065–73.

    Article  PubMed  Google Scholar 

  166. Shaw P, Greenstein D, Lerch J, Clasen L, Lenroot R, Gogtay N, et al. Intellectual ability and cortical development in children and adolescents. Nature. 2006;440(7084):676–9.

    Article  PubMed  CAS  Google Scholar 

  167. Sowell ER, Thompson PM, Leonard CM, Welcome SE, Kan E, Toga AW. Longitudinal mapping of cortical thickness and brain growth in normal children. J Neurosci. 2004;24(38):8223–31.

    Article  PubMed  CAS  Google Scholar 

  168. Giedd JN, Castellanos FX, Rajapakse JC, Vaituzis AC, Rapoport JL. Sexual dimorphism of the developing human brain. Progr Neuro Psychopharmacol Biol Psychiatr. 1997;21(8):1185–201.

    Article  CAS  Google Scholar 

  169. Raznahan A, Lee Y, Stidd R, Long R, Greenstein D, Clasen L, et al. Longitudinally mapping the influence of sex and androgen signaling on the dynamics of human cortical maturation in adolescence. Proc Natl Acad Sci USA. 2010;107(39):16988–93.

    Article  PubMed  CAS  Google Scholar 

  170. Reid SN, Juraska JM. Sex differences in the gross size of the rat neocortex. J Comp Neurol. 1992;321(3):442–7.

    Article  PubMed  CAS  Google Scholar 

  171. Nunez JL, Sodhi J, Juraska JM. Ovarian hormones after postnatal day 20 reduce neuron number in the rat primary visual cortex. J Neurobiol. 2002;52(4):312–21.

    Article  PubMed  CAS  Google Scholar 

  172. Kim JH, Juraska JM. Sex differences in the development of axon number in the splenium of the rat corpus callosum from postnatal day 15 through 60. Brain Res. 1997;102(1):77–85.

    Article  CAS  Google Scholar 

  173. Yates MA, Juraska JM. Pubertal ovarian hormone exposure reduces the number of myelinated axons in the splenium of the rat corpus callosum. Exp Neurol. 2008;209(1):284–7.

    Article  PubMed  CAS  Google Scholar 

  174. Rubinow MJ, Juraska JM. Neuron and glia numbers in the basolateral nucleus of the amygdala from preweaning through old age in male and female rats: a stereological study. J Comp Neurol. 2009;512(6):717–25.

    Article  PubMed  Google Scholar 

  175. Koss WA, Belden CE, Decker SK, Juraska JM. Dendritic remodeling over the adolescent period in the basolateral amygdala of male and female rats. Society for Neuroscience Abstracts. 2009:508.8.

  176. Zehr JL, Todd BJ, Schulz KM, McCarthy MM, Sisk CL. Dendritic pruning of the medial amygdala during pubertal development of the male syrian hamster. J Neurobiol. 2006;66(6):578–90.

    Article  PubMed  Google Scholar 

  177. Ahmed EI, Zehr JL, Schulz KM, Lorenz BH, DonCarlos LL, Sisk CL. Pubertal hormones modulate the addition of new cells to sexually dimorphic brain regions. Nat Neurosci. 2008;11(9):995–7.

    Article  PubMed  CAS  Google Scholar 

  178. Meyer G, Ferres-Torres R, Mas M. The effects of puberty and castration on hippocampal dendritic spines of mice. A golgi study. Brain Res. 1978;155(1):108–12.

    Article  PubMed  CAS  Google Scholar 

  179. Teicher MH, Andersen SL, Hostetter Jr JC. Evidence for dopamine receptor pruning between adolescence and adulthood in striatum but not nucleus accumbens. Brain Res. 1995;89(2):167–72.

    Article  CAS  Google Scholar 

  180. Andersen SL, Thompson AT, Rutstein M, Hostetter JC, Teicher MH. Dopamine receptor pruning in prefrontal cortex during the periadolescent period in rats. Synapse NY NY. 2000;37(2):167–9.

    Article  CAS  Google Scholar 

  181. Andersen SL, Rutstein M, Benzo JM, Hostetter JC, Teicher MH. Sex differences in dopamine receptor overproduction and elimination. Neuroreport. 1997;8(6):1495–8.

    Article  PubMed  CAS  Google Scholar 

  182. Andersen SL, Thompson AP, Krenzel E, Teicher MH. Pubertal changes in gonadal hormones do not underlie adolescent dopamine receptor overproduction. Psychoneuroendocrinology. 2002;27(6):683–91.

    Article  PubMed  CAS  Google Scholar 

  183. Kalsbeek A, Voorn P, Buijs RM, Pool CW, Uylings HB. Development of the dopaminergic innervation in the prefrontal cortex of the rat. J Comp Neurol. 1988;269(1):58–72.

    Article  PubMed  CAS  Google Scholar 

  184. Benes FM, Vincent SL, Molloy R, Khan Y. Increased interaction of dopamine-immunoreactive varicosities with gaba neurons of rat medial prefrontal cortex occurs during the postweanling period. Synapse NY NY. 1996;23(4):237–45.

    Article  CAS  Google Scholar 

  185. Tseng KY, O’Donnell P. D2 dopamine receptors recruit a gaba component for their attenuation of excitatory synaptic transmission in the adult rat prefrontal cortex. Synapse NY NY. 2007;61(10):843–50.

    Article  CAS  Google Scholar 

  186. Tseng KY, O’Donnell P. Dopamine modulation of prefrontal cortical interneurons changes during adolescence. Cereb Cortex. 2007;17(5):1235–40.

    Article  PubMed  Google Scholar 

  187. Heng L, Markham JA, Hu XT, Tseng KY. Concurrent upregulation of postsynaptic l-type ca(2+) channel function and protein kinase a signaling is required for the periadolescent facilitation of ca(2+) plateau potentials and dopamine d1 receptor modulation in the prefrontal cortex. Neuropharmacology. in press.

  188. Cunningham MG, Bhattacharyya S, Benes FM. Amygdalo-cortical sprouting continues into early adulthood: Implications for the development of normal and abnormal function during adolescence. J Comp Neurol. 2002;453(2):116–30.

    Article  PubMed  Google Scholar 

  189. Cressman VL, Balaban J, Steinfeld S, Shemyakin A, Graham P, Parisot N, et al. Prefrontal cortical inputs to the basal amygdala undergo pruning during late adolescence in the rat. J Comp Neurol. 2010;518(14):2693–709.

    PubMed  CAS  Google Scholar 

  190. Becker JB. Gender differences in dopaminergic function in striatum and nucleus accumbens. Pharmacol Biochem Behav. 1999;64(4):803–12.

    Article  PubMed  CAS  Google Scholar 

  191. Shrenker P, Maxson SC, Ginsburg BE. The role of postnatal testosterone in the development of sexually dimorphic behaviors in dba/1bg mice. Physiol Behav. 1985;35(5):757–62.

    Article  PubMed  CAS  Google Scholar 

  192. Eichmann F, Holst DV. Organization of territorial marking behavior by testosterone during puberty in male tree shrews. Physiol Behav. 1999;65(4–5):785–91.

    PubMed  CAS  Google Scholar 

  193. Pellis SM. Sex differences in play fighting revisited: traditional and nontraditional mechanisms of sexual differentiation in rats. Arch Sex Behav. 2002;31(1):17–26.

    Article  PubMed  Google Scholar 

  194. Schulz KM, Zehr JL, Salas-Ramirez KY, Sisk CL. Testosterone programs adult social behavior before and during, but not after, adolescence. Endocrinology. 2009;150(8):3690–8.

    Article  PubMed  CAS  Google Scholar 

  195. Brand T, Slob AK. Peripubertal castration of male rats, adult open field ambulation and partner preference behavior. Behav Brain Res. 1988;30(2):111–7.

    Article  PubMed  CAS  Google Scholar 

  196. Primus RJ, Kellogg CK. Gonadal hormones during puberty organize environment-related social interaction in the male rat. Horm Behav. 1990;24(3):311–23.

    Article  PubMed  CAS  Google Scholar 

  197. Levin HS, Culhane KA, Hartmann J, Evankovich K, Mattson AJ, Harward H, et al. Developmental changes in performance on tests of purported frontal lobe functioning. Dev Neuropsych. 1991;7(3):377–95.

    Article  Google Scholar 

  198. Kanit L, Taskiran D, Yilmaz OA, Balkan B, Demirgoren S, Furedy JJ, et al. Sexually dimorphic cognitive style in rats emerges after puberty. Brain Res Bull. 2000;52(4):243–8.

    Article  PubMed  CAS  Google Scholar 

  199. Hier DB, Crowley Jr WF. Spatial ability in androgen-deficient men. N Engl J Med. 1982;306(20):1202–5.

    Article  PubMed  CAS  Google Scholar 

  200. Markham JA. Peri-adolescent gonadal steroids organize adult sex differences in prefrontal-dependent extinction of a conditioned fear memory. In preparation.

  201. Morgan MA, LeDoux JE. Differential contribution of dorsal and ventral medial prefrontal cortex to the acquisition and extinction of conditioned fear in rats. Behav Neurosci. 1995;109(4):681–8.

    Article  PubMed  CAS  Google Scholar 

  202. Van den Buuse M, Eikelis N. Estrogen increases prepulse inhibition of acoustic startle in rats. Eur J Pharmacol. 2001;425(1):33–41.

    Article  PubMed  Google Scholar 

  203. Gogos A, Nathan PJ, Guille V, Croft RJ, van den Buuse M. Estrogen prevents 5-ht1a receptor-induced disruptions of prepulse inhibition in healthy women. Neuropsychopharmacology. 2006;31(4):885–9.

    Article  PubMed  CAS  Google Scholar 

  204. Weiner I. The “Two-headed” Latent inhibition model of schizophrenia: modeling positive and negative symptoms and their treatment. Psychopharmacology. 2003;169(3–4):257–97.

    Article  PubMed  CAS  Google Scholar 

  205. Nofrey BS, Ben-Shahar OM, Brake WG. Estrogen abolishes latent inhibition in ovariectomized female rats. Brain Cogn. 2008;66(2):156–60.

    Article  PubMed  Google Scholar 

  206. Arad M, Weiner I. Disruption of latent inhibition induced by ovariectomy can be reversed by estradiol and clozapine as well as by co-administration of haloperidol with estradiol but not by haloperidol alone. Psychopharmacology. 2009;206(4):731–40.

    Article  PubMed  CAS  Google Scholar 

  207. Arad M, Weiner I. Sex-dependent antipsychotic capacity of 17beta-estradiol in the latent inhibition model: a typical antipsychotic drug in both sexes, atypical antipsychotic drug in males. Neuropsychopharmacology. 2010;35(11):2179–92.

    Article  PubMed  CAS  Google Scholar 

  208. Koller WC, Weiner WJ, Klawans HL, Nausieda PA. Influence of female sex hormones on neuroleptic-induced behavioral supersensitivity. Neuropharmacology. 1980;19(4):387–91.

    Article  PubMed  CAS  Google Scholar 

  209. Foreman MM, Porter JC. Effects of catechol estrogens and catecholamines on hypothalamic and corpus striatal tyrosine hydroxylase activity. J Neurochem. 1980;34(5):1175–83.

    Article  PubMed  CAS  Google Scholar 

  210. Bedard P, Boucher R, Di Paolo T, Labrie F. Interaction between estradiol, prolactin, and striatal dopaminergic mechanisms. Adv Neurol. 1984;40:489–95.

    PubMed  CAS  Google Scholar 

  211. Bedard PJ, Boucher R, Daigle M, Di Paolo T. Similar effect of estradiol and haloperidol on experimental tardive dyskinesia in monkeys. Psychoneuroendocrinology. 1984;9(4):375–9.

    Article  PubMed  CAS  Google Scholar 

  212. Hafner H, Behrens S, De Vry J, Gattaz WF. An animal model for the effects of estradiol on dopamine-mediated behavior: implications for sex differences in schizophrenia. Psychiatry Res. 1991;38(2):125–34.

    Article  PubMed  CAS  Google Scholar 

  213. Swerdlow NR, Auerbach P, Monroe SM, Hartston H, Geyer MA, Braff DL. Men are more inhibited than women by weak prepulses. Biol Psychiatry. 1993;34(4):253–60.

    Article  PubMed  CAS  Google Scholar 

  214. Swerdlow NR, Hartman PL, Auerbach PP. Changes in sensorimotor inhibition across the menstrual cycle: implications for neuropsychiatric disorders. Biol Psychiatry. 1997;41(4):452–60.

    Article  PubMed  CAS  Google Scholar 

  215. Koch M. Sensorimotor gating changes across the estrous cycle in female rats. Physiol Behav. 1998;64(5):625–8.

    Article  PubMed  CAS  Google Scholar 

  216. Becker JB. Direct effect of 17 beta-estradiol on striatum: sex differences in dopamine release. Synapse NY NY. 1990;5(2):157–64.

    Article  CAS  Google Scholar 

  217. Markham JA, Juraska JM. Social recognition memory: influence of age, sex, and ovarian hormonal status. Physiol Behav. 2007;92(5):881–8.

    Article  PubMed  CAS  Google Scholar 

  218. Thor DH. Testosterone and persistance of social investigation in laboratory rats. J Comp Physiol Psychol. 1980;94(5):970–6.

    Article  PubMed  CAS  Google Scholar 

  219. Thor DH, Wainwright KL, Holloway WR. Persistence of attention to a novel conspecific: some developmental variables in laboratory rats. Dev Psychobiol. 1982;15(1):1–8.

    Article  PubMed  CAS  Google Scholar 

  220. Dohanich GP. Gonadal steroids, learning and memoroy. In: Pfaff DW, Arnold AP, Etgen SE, Fahrbach SE, Rubin RT, editors. Hormones, brain and behavior. San Diego: Academic Press (Elsevier Science); 2002. p. 265–327.

    Chapter  Google Scholar 

  221. Jonasson Z. Meta-analysis of sex differences in rodent models of learning and memory: a review of behavioral and biological data. Neurosci Biobehav Rev. 2005;28(8):811–25.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This work is supported by the National Institute of Child Health Human Development and the Office of Research on Women’s Health, through a Building Interdisciplinary Research Careers in Women’s Health (BIRCWH) Scholarship to J.M. (K12HD043489). The author also wishes to thank Dr. Brent Orr for his thoughtful comments on the manuscript.

Author information

Authors and Affiliations

  1. Maryland Psychiatric Research Center, University of Maryland-Baltimore School of Medicine, P.O. Box 21247, Baltimore, MD, 21228, USA

    Julie A. Markham

  2. Maryland Psychiatric Research Center, Department of Psychiatry, and Program in Neuroscience, University of Maryland-Baltimore School of Medicine, Baltimore, MD, 21228, USA

    Julie A. Markham

Authors
  1. Julie A. Markham
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Julie A. Markham.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Markham, J.A. Sex steroids and schizophrenia. Rev Endocr Metab Disord 13, 187–207 (2012). https://doi.org/10.1007/s11154-011-9184-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11154-011-9184-2

Keywords

Search

Navigation