Reviews in Endocrine and Metabolic Disorders

, Volume 13, Issue 3, pp 187–207 | Cite as

Sex steroids and schizophrenia

  • Julie A. Markham


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.


Estrogen Testosterone Psychosis Gonadal hormones Sex differences Animal models 



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.


  1. 1.
    Seeman MV. Psychopathology in women and men: focus on female hormones. Am J Psychiatry. 1997;154(12):1641–7.PubMedGoogle Scholar
  2. 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.PubMedCrossRefGoogle Scholar
  3. 3.
    Saha S, Chant D, Welham J, McGrath J. A systematic review of the prevalence of schizophrenia. PLoS Med. 2005;2(5):e141.PubMedCrossRefGoogle Scholar
  4. 4.
    Tsuang M. Schizophrenia: genes and environment. Biol Psychiatry. 2000;47(3):210–20.PubMedCrossRefGoogle Scholar
  5. 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.PubMedCrossRefGoogle Scholar
  6. 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.PubMedCrossRefGoogle Scholar
  7. 7.
    Kraepelin E. Psychiatrie. Leipzig: Barth; 1909.Google Scholar
  8. 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.PubMedCrossRefGoogle Scholar
  9. 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.PubMedCrossRefGoogle Scholar
  10. 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.PubMedCrossRefGoogle Scholar
  11. 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.PubMedGoogle Scholar
  12. 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.PubMedCrossRefGoogle Scholar
  13. 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.PubMedCrossRefGoogle Scholar
  14. 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.PubMedCrossRefGoogle Scholar
  15. 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.PubMedCrossRefGoogle Scholar
  16. 16.
    Munk-Jorgensen P. First-admission rates and marital status of schizophrenics. Acta Psychiatr Scand. 1987;76(2):210–6.PubMedCrossRefGoogle Scholar
  17. 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.PubMedCrossRefGoogle Scholar
  18. 18.
    Albus M, Maier W. Lack of gender differences in age at onset in familial schizophrenia. Schizophr Res. 1995;18(1):51–7.PubMedCrossRefGoogle Scholar
  19. 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.PubMedGoogle Scholar
  20. 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.PubMedCrossRefGoogle Scholar
  21. 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.PubMedCrossRefGoogle Scholar
  22. 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.PubMedCrossRefGoogle Scholar
  23. 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.PubMedCrossRefGoogle Scholar
  24. 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. 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.PubMedCrossRefGoogle Scholar
  26. 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.PubMedCrossRefGoogle Scholar
  27. 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.PubMedCrossRefGoogle Scholar
  28. 28.
    Angermeyer MC, Goldstein JM, Kuehn L. Gender differences in schizophrenia: rehospitalization and community survival. Psychol Med. 1989;19(2):365–82.PubMedCrossRefGoogle Scholar
  29. 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.PubMedCrossRefGoogle Scholar
  30. 30.
    Salokangas RK. Prognostic implications of the sex of schizophrenic patients. Br J Psychiatry. 1983;142:145–51.PubMedCrossRefGoogle Scholar
  31. 31.
    Seeman MV. Current outcome in schizophrenia: women vs men. Acta Psychiatr Scand. 1986;73(6):609–17.PubMedCrossRefGoogle Scholar
  32. 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.PubMedCrossRefGoogle Scholar
  33. 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.PubMedCrossRefGoogle Scholar
  34. 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.PubMedCrossRefGoogle Scholar
  35. 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.PubMedCrossRefGoogle Scholar
  36. 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.PubMedGoogle Scholar
  37. 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.PubMedCrossRefGoogle Scholar
  38. 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.PubMedCrossRefGoogle Scholar
  39. 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.PubMedCrossRefGoogle Scholar
  40. 40.
    Tanaka E. Gender-related differences in pharmacokinetics and their clinical significance. J Clin Pharm Ther. 1999;24(5):339–46.PubMedCrossRefGoogle Scholar
  41. 41.
    DeLisi LE. The significance of age of onset for schizophrenia. Schizophr Bull. 1992;18(2):209–15.PubMedGoogle Scholar
  42. 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.PubMedCrossRefGoogle Scholar
  43. 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.CrossRefGoogle Scholar
  44. 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.PubMedCrossRefGoogle Scholar
  45. 45.
    Goldstein JM, Link BG. Gender and the expression of schizophrenia. J Psychiatr Res. 1988;22(2):141–55.PubMedCrossRefGoogle Scholar
  46. 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.PubMedCrossRefGoogle Scholar
  47. 47.
    McGlashan TH, Bardenstein KK. Gender differences in affective, schizoaffective, and schizophrenic disorders. Schizophr Bull. 1990;16(2):319–29.PubMedGoogle Scholar
  48. 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.PubMedCrossRefGoogle Scholar
  49. 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.PubMedGoogle Scholar
  50. 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.PubMedCrossRefGoogle Scholar
  51. 51.
    Nopoulos P, Flaum M, Andreasen NC. Sex differences in brain morphology in schizophrenia. Am J Psychiatry. 1997;154(12):1648–54.PubMedGoogle Scholar
  52. 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.PubMedCrossRefGoogle Scholar
  53. 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.PubMedGoogle Scholar
  54. 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.PubMedGoogle Scholar
  55. 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.PubMedGoogle Scholar
  56. 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.PubMedGoogle Scholar
  57. 57.
    Walker EF, Lewine RR. Sampling biases in studies of gender and schizophrenia. Schizophr Bull. 1993;19(1):1–7. discussion 9–14.PubMedGoogle Scholar
  58. 58.
    Goldstein JM. Sampling biases in studies of gender and schizophrenia: a reply. Schizophr Bull. 1993;19(1):9–14.Google Scholar
  59. 59.
    Kendell RE, Chalmers JC, Platz C. Epidemiology of puerperal psychoses. Br J Psychiatry. 1987;150:662–73.PubMedCrossRefGoogle Scholar
  60. 60.
    Mahe V, Dumaine A. Oestrogen withdrawal associated psychoses. Acta Psychiatr Scand. 2001;104(5):323–31.PubMedCrossRefGoogle Scholar
  61. 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.CrossRefGoogle Scholar
  62. 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.PubMedCrossRefGoogle Scholar
  63. 63.
    Riecher-Rossler A, Hafner H, Stumbaum M, Maurer K, Schmidt R. Can estradiol modulate schizophrenic symptomatology? Schizophr Bull. 1994;20(1):203–14.PubMedGoogle Scholar
  64. 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.PubMedCrossRefGoogle Scholar
  65. 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.PubMedCrossRefGoogle Scholar
  66. 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.PubMedCrossRefGoogle Scholar
  67. 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.PubMedCrossRefGoogle Scholar
  68. 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.PubMedCrossRefGoogle Scholar
  69. 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.CrossRefGoogle Scholar
  70. 70.
    Felthous AR, Robinson DB, Conroy RW. Prevention of recurrent menstrual psychosis by an oral contraceptive. Am J Psychiatry. 1980;137(2):245–6.PubMedGoogle Scholar
  71. 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.CrossRefGoogle Scholar
  72. 72.
    Lindamer LA, Lohr JB, Harris MJ, Jeste DV. Gender, estrogen, and schizophrenia. Psychopharmacol Bull. 1997;33(2):221–8.PubMedGoogle Scholar
  73. 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.PubMedCrossRefGoogle Scholar
  74. 74.
    Di Paolo T. Modulation of brain dopamine transmission by sex steroids. Rev Neurosci. 1994;5(1):27–41.PubMedCrossRefGoogle Scholar
  75. 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.PubMedCrossRefGoogle Scholar
  76. 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.PubMedCrossRefGoogle Scholar
  77. 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.PubMedGoogle Scholar
  78. 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.PubMedCrossRefGoogle Scholar
  79. 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.PubMedCrossRefGoogle Scholar
  80. 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.PubMedCrossRefGoogle Scholar
  81. 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.PubMedCrossRefGoogle Scholar
  82. 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.PubMedCrossRefGoogle Scholar
  83. 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.PubMedCrossRefGoogle Scholar
  84. 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.PubMedCrossRefGoogle Scholar
  85. 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.PubMedCrossRefGoogle Scholar
  86. 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.CrossRefGoogle Scholar
  87. 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.PubMedCrossRefGoogle Scholar
  88. 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.CrossRefGoogle Scholar
  89. 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.PubMedCrossRefGoogle Scholar
  90. 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.PubMedCrossRefGoogle Scholar
  91. 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.PubMedCrossRefGoogle Scholar
  92. 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.PubMedCrossRefGoogle Scholar
  93. 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.PubMedCrossRefGoogle Scholar
  94. 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.PubMedCrossRefGoogle Scholar
  95. 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.PubMedCrossRefGoogle Scholar
  96. 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.PubMedCrossRefGoogle Scholar
  97. 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.PubMedCrossRefGoogle Scholar
  98. 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.CrossRefGoogle Scholar
  99. 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.PubMedGoogle Scholar
  100. 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.PubMedCrossRefGoogle Scholar
  101. 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.PubMedCrossRefGoogle Scholar
  102. 102.
    Tourney G, Erb JL. Temporal variations in androgens and stress hormones in control and schizophrenic subjects. Biol Psychiatry. 1979;14(2):395–404.PubMedGoogle Scholar
  103. 103.
    Tourney G, Hatfield L. Plasma androgens in male schizophrenics. Arch Gen Psychiatry. 1972;27(6):753–5.PubMedCrossRefGoogle Scholar
  104. 104.
    Ferrier IN, Cotes PM, Crow TJ, Johnstone EC. Gonadotropin secretion abnormalities in chronic schizophrenia. Psychol Med. 1982;12(2):263–73.PubMedCrossRefGoogle Scholar
  105. 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.Google Scholar
  106. 106.
    Oades RD, Schepker R. Serum gonadal steroid hormones in young schizophrenic patients. Psychoneuroendocrinology. 1994;19(4):373–85.PubMedCrossRefGoogle Scholar
  107. 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.PubMedCrossRefGoogle Scholar
  108. 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.PubMedCrossRefGoogle Scholar
  109. 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.PubMedCrossRefGoogle Scholar
  110. 110.
    Brophy MH, Rush AJ, Crowley G. Cortisol, estradiol, and androgens in acutely ill paranoid schizophrenics. Biol Psychiatry. 1983;18(5):583–90.PubMedGoogle Scholar
  111. 111.
    Ceskova E, Prikryl R, Kasparek T. Testosterone in first-episode schizophrenia. Neuro Endocrinol Lett. 2007;28(6):811–4.PubMedGoogle Scholar
  112. 112.
    Huber TJ, Tettenborn C, Leifke E, Emrich HM. Sex hormones in psychotic men. Psychoneuroendocrinology. 2005;30(1):111–4.PubMedCrossRefGoogle Scholar
  113. 113.
    Taherianfard M, Shariaty M. Evaluation of serum steroid hormones in schizophrenic patients. Indian J Med Sci. 2004;58(1):3–9.PubMedGoogle Scholar
  114. 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.PubMedCrossRefGoogle Scholar
  115. 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.PubMedCrossRefGoogle Scholar
  116. 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.PubMedCrossRefGoogle Scholar
  117. 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.PubMedCrossRefGoogle Scholar
  118. 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.PubMedCrossRefGoogle Scholar
  119. 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.PubMedCrossRefGoogle Scholar
  120. 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.PubMedCrossRefGoogle Scholar
  121. 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.PubMedCrossRefGoogle Scholar
  122. 122.
    Strous RD. Dehydroepiandrosterone (dhea) augmentation in the management of schizophrenia symptomatology. Essent Psychopharmacol. 2005;6(3):141–7.PubMedGoogle Scholar
  123. 123.
    Baulieu EE, Robel P. Dehydroepiandrosterone and dehydroepiandrosterone sulfate as neuroactive neurosteroids. J Endocrinol. 1996;150(Suppl):S221–39.PubMedGoogle Scholar
  124. 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.PubMedCrossRefGoogle Scholar
  125. 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.PubMedCrossRefGoogle Scholar
  126. 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.PubMedCrossRefGoogle Scholar
  127. 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.Google Scholar
  128. 128.
    Koenig JI, Kirkpatrick B, Lee P. Glucocorticoid hormones and early brain development in schizophrenia. Neuropsychopharmacology. 2002;27(2):309–18.PubMedCrossRefGoogle Scholar
  129. 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.PubMedCrossRefGoogle Scholar
  130. 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.PubMedCrossRefGoogle Scholar
  131. 131.
    Clancy B, Darlington RB, Finlay BL. Translating developmental time across mammalian species. Neuroscience. 2001;105(1):7–17.PubMedCrossRefGoogle Scholar
  132. 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.PubMedCrossRefGoogle Scholar
  133. 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.PubMedCrossRefGoogle Scholar
  134. 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.PubMedCrossRefGoogle Scholar
  135. 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. 136.
    Markham JA, Koenig JI. Prenatal stress: role in psychotic and depressive diseases. Psychopharmacology. in press.Google Scholar
  137. 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.Google Scholar
  138. 138.
    Guillin O, Abi-Dargham A, Laruelle M. Neurobiology of dopamine in schizophrenia. Int Rev Neurobiol. 2007;78:1–39.PubMedCrossRefGoogle Scholar
  139. 139.
    Creese I, Iversen SD. The pharmacological and anatomical substrates of the amphetamine response in the rat. Brain Res. 1975;83(3):419–36.PubMedCrossRefGoogle Scholar
  140. 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.Google Scholar
  141. 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.Google Scholar
  142. 142.
    Steckler T, Drinkenburg WH, Sahgal A, Aggleton JP. Recognition memory in rats–ii. Neuroanatomical substrates. Prog Neurobiol. 1998;54(3):313–32.PubMedCrossRefGoogle Scholar
  143. 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.PubMedGoogle Scholar
  144. 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.PubMedCrossRefGoogle Scholar
  145. 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.PubMedCrossRefGoogle Scholar
  146. 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.PubMedCrossRefGoogle Scholar
  147. 147.
    Brown AS, Susser ES. In utero infection and adult schizophrenia. Ment Retard Dev Disabil Res Rev. 2002;8(1):51–7.PubMedCrossRefGoogle Scholar
  148. 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.PubMedCrossRefGoogle Scholar
  149. 149.
    Markham JA. Sex steroids and schizophrenia. Reviews in Endocrine and Metabolic Disorders. accepted in revision.Google Scholar
  150. 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.PubMedCrossRefGoogle Scholar
  151. 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.PubMedCrossRefGoogle Scholar
  152. 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.PubMedCrossRefGoogle Scholar
  153. 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.PubMedCrossRefGoogle Scholar
  154. 154.
    Powell SB, Zhou X, Geyer MA. Prepulse inhibition and genetic mouse models of schizophrenia. Behav Brain Res. 2009;204(2):282–94.PubMedCrossRefGoogle Scholar
  155. 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.PubMedCrossRefGoogle Scholar
  156. 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.Google Scholar
  157. 157.
    Kumari V, Aasen I, Sharma T. Sex differences in prepulse inhibition deficits in chronic schizophrenia. Schizophr Res. 2004;69(2–3):219–35.PubMedCrossRefGoogle Scholar
  158. 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.PubMedCrossRefGoogle Scholar
  159. 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.PubMedCrossRefGoogle Scholar
  160. 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.CrossRefGoogle Scholar
  161. 161.
    Morris JA, Jordan CL, Breedlove SM. Sexual differentiation of the vertebrate nervous system. Nat Neurosci. 2004;7(10):1034–9.PubMedCrossRefGoogle Scholar
  162. 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.PubMedCrossRefGoogle Scholar
  163. 163.
    Lewis DA, Sweet RA. Schizophrenia from a neural circuitry perspective: advancing toward rational pharmacological therapies. J Clin Investig. 2009;119(4):706–16.PubMedCrossRefGoogle Scholar
  164. 164.
    Stander N, Wagner WM, Goddard A, Kirberger RM. Ultrasonographic appearance of canine parvoviral enteritis in puppies. Vet Radiol Ultrasound. 51(1):69–74.Google Scholar
  165. 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.PubMedCrossRefGoogle Scholar
  166. 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.PubMedCrossRefGoogle Scholar
  167. 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.PubMedCrossRefGoogle Scholar
  168. 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.CrossRefGoogle Scholar
  169. 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.PubMedCrossRefGoogle Scholar
  170. 170.
    Reid SN, Juraska JM. Sex differences in the gross size of the rat neocortex. J Comp Neurol. 1992;321(3):442–7.PubMedCrossRefGoogle Scholar
  171. 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.PubMedCrossRefGoogle Scholar
  172. 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.CrossRefGoogle Scholar
  173. 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.PubMedCrossRefGoogle Scholar
  174. 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.PubMedCrossRefGoogle Scholar
  175. 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.Google Scholar
  176. 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.PubMedCrossRefGoogle Scholar
  177. 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.PubMedCrossRefGoogle Scholar
  178. 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.PubMedCrossRefGoogle Scholar
  179. 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.CrossRefGoogle Scholar
  180. 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.CrossRefGoogle Scholar
  181. 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.PubMedCrossRefGoogle Scholar
  182. 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.PubMedCrossRefGoogle Scholar
  183. 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.PubMedCrossRefGoogle Scholar
  184. 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.CrossRefGoogle Scholar
  185. 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.CrossRefGoogle Scholar
  186. 186.
    Tseng KY, O’Donnell P. Dopamine modulation of prefrontal cortical interneurons changes during adolescence. Cereb Cortex. 2007;17(5):1235–40.PubMedCrossRefGoogle Scholar
  187. 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.Google Scholar
  188. 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.PubMedCrossRefGoogle Scholar
  189. 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.PubMedGoogle Scholar
  190. 190.
    Becker JB. Gender differences in dopaminergic function in striatum and nucleus accumbens. Pharmacol Biochem Behav. 1999;64(4):803–12.PubMedCrossRefGoogle Scholar
  191. 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.PubMedCrossRefGoogle Scholar
  192. 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.PubMedGoogle Scholar
  193. 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.PubMedCrossRefGoogle Scholar
  194. 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.PubMedCrossRefGoogle Scholar
  195. 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.PubMedCrossRefGoogle Scholar
  196. 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.PubMedCrossRefGoogle Scholar
  197. 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.CrossRefGoogle Scholar
  198. 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.PubMedCrossRefGoogle Scholar
  199. 199.
    Hier DB, Crowley Jr WF. Spatial ability in androgen-deficient men. N Engl J Med. 1982;306(20):1202–5.PubMedCrossRefGoogle Scholar
  200. 200.
    Markham JA. Peri-adolescent gonadal steroids organize adult sex differences in prefrontal-dependent extinction of a conditioned fear memory. In preparation.Google Scholar
  201. 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.PubMedCrossRefGoogle Scholar
  202. 202.
    Van den Buuse M, Eikelis N. Estrogen increases prepulse inhibition of acoustic startle in rats. Eur J Pharmacol. 2001;425(1):33–41.PubMedCrossRefGoogle Scholar
  203. 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.PubMedCrossRefGoogle Scholar
  204. 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.PubMedCrossRefGoogle Scholar
  205. 205.
    Nofrey BS, Ben-Shahar OM, Brake WG. Estrogen abolishes latent inhibition in ovariectomized female rats. Brain Cogn. 2008;66(2):156–60.PubMedCrossRefGoogle Scholar
  206. 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.PubMedCrossRefGoogle Scholar
  207. 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.PubMedCrossRefGoogle Scholar
  208. 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.PubMedCrossRefGoogle Scholar
  209. 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.PubMedCrossRefGoogle Scholar
  210. 210.
    Bedard P, Boucher R, Di Paolo T, Labrie F. Interaction between estradiol, prolactin, and striatal dopaminergic mechanisms. Adv Neurol. 1984;40:489–95.PubMedGoogle Scholar
  211. 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.PubMedCrossRefGoogle Scholar
  212. 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.PubMedCrossRefGoogle Scholar
  213. 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.PubMedCrossRefGoogle Scholar
  214. 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.PubMedCrossRefGoogle Scholar
  215. 215.
    Koch M. Sensorimotor gating changes across the estrous cycle in female rats. Physiol Behav. 1998;64(5):625–8.PubMedCrossRefGoogle Scholar
  216. 216.
    Becker JB. Direct effect of 17 beta-estradiol on striatum: sex differences in dopamine release. Synapse NY NY. 1990;5(2):157–64.CrossRefGoogle Scholar
  217. 217.
    Markham JA, Juraska JM. Social recognition memory: influence of age, sex, and ovarian hormonal status. Physiol Behav. 2007;92(5):881–8.PubMedCrossRefGoogle Scholar
  218. 218.
    Thor DH. Testosterone and persistance of social investigation in laboratory rats. J Comp Physiol Psychol. 1980;94(5):970–6.PubMedCrossRefGoogle Scholar
  219. 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.PubMedCrossRefGoogle Scholar
  220. 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.CrossRefGoogle Scholar
  221. 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.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Maryland Psychiatric Research CenterUniversity of Maryland-Baltimore School of MedicineBaltimoreUSA
  2. 2.Maryland Psychiatric Research Center, Department of Psychiatry, and Program in NeuroscienceUniversity of Maryland-Baltimore School of MedicineBaltimoreUSA

Personalised recommendations