Date: 21 May 2011
Sex steroids and schizophrenia
- Julie A. Markham
- … show all 1 hide
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
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.
Seeman MV. Psychopathology in women and men: focus on female hormones. Am J Psychiatry. 1997;154(12):1641–7.PubMed
Kraepelin E. Psychiatrie. Leipzig: Barth; 1909.
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.PubMedCrossRef
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
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
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.
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
DeLisi LE. The significance of age of onset for schizophrenia. Schizophr Bull. 1992;18(2):209–15.PubMed
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.CrossRef
McGlashan TH, Bardenstein KK. Gender differences in affective, schizoaffective, and schizophrenic disorders. Schizophr Bull. 1990;16(2):319–29.PubMed
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
Nopoulos P, Flaum M, Andreasen NC. Sex differences in brain morphology in schizophrenia. Am J Psychiatry. 1997;154(12):1648–54.PubMed
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
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
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
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
Walker EF, Lewine RR. Sampling biases in studies of gender and schizophrenia. Schizophr Bull. 1993;19(1):1–7. discussion 9–14.PubMed
Goldstein JM. Sampling biases in studies of gender and schizophrenia: a reply. Schizophr Bull. 1993;19(1):9–14.
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.CrossRef
Riecher-Rossler A, Hafner H, Stumbaum M, Maurer K, Schmidt R. Can estradiol modulate schizophrenic symptomatology? Schizophr Bull. 1994;20(1):203–14.PubMed
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.CrossRef
Felthous AR, Robinson DB, Conroy RW. Prevention of recurrent menstrual psychosis by an oral contraceptive. Am J Psychiatry. 1980;137(2):245–6.PubMed
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.CrossRef
Lindamer LA, Lohr JB, Harris MJ, Jeste DV. Gender, estrogen, and schizophrenia. Psychopharmacol Bull. 1997;33(2):221–8.PubMed
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
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.CrossRef
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.CrossRef
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.CrossRef
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
Tourney G, Erb JL. Temporal variations in androgens and stress hormones in control and schizophrenic subjects. Biol Psychiatry. 1979;14(2):395–404.PubMed
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.
Brophy MH, Rush AJ, Crowley G. Cortisol, estradiol, and androgens in acutely ill paranoid schizophrenics. Biol Psychiatry. 1983;18(5):583–90.PubMed
Ceskova E, Prikryl R, Kasparek T. Testosterone in first-episode schizophrenia. Neuro Endocrinol Lett. 2007;28(6):811–4.PubMed
Taherianfard M, Shariaty M. Evaluation of serum steroid hormones in schizophrenic patients. Indian J Med Sci. 2004;58(1):3–9.PubMed
Strous RD. Dehydroepiandrosterone (dhea) augmentation in the management of schizophrenia symptomatology. Essent Psychopharmacol. 2005;6(3):141–7.PubMed
Baulieu EE, Robel P. Dehydroepiandrosterone and dehydroepiandrosterone sulfate as neuroactive neurosteroids. J Endocrinol. 1996;150(Suppl):S221–39.PubMed
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.PubMedCrossRef
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.PubMedCrossRef
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.
Markham JA, Koenig JI. Prefrontal neuronal architecture is disrupted in the rat prenatal stress model of schizophrenia. Schizophr Bull. 2009;35(Supplement 1):137.
Markham JA, Koenig JI. Prenatal stress: role in psychotic and depressive diseases. Psychopharmacology. in press.
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.
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.
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.
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
Markham JA. Sex steroids and schizophrenia. Reviews in Endocrine and Metabolic Disorders. accepted in revision.
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.
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.CrossRef
Stander N, Wagner WM, Goddard A, Kirberger RM. Ultrasonographic appearance of canine parvoviral enteritis in puppies. Vet Radiol Ultrasound. 51(1):69–74.
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.CrossRef
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.CrossRef
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.
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.CrossRef
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.CrossRef
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.CrossRef
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.CrossRef
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.
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
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
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.CrossRef
Markham JA. Peri-adolescent gonadal steroids organize adult sex differences in prefrontal-dependent extinction of a conditioned fear memory. In preparation.
Bedard P, Boucher R, Di Paolo T, Labrie F. Interaction between estradiol, prolactin, and striatal dopaminergic mechanisms. Adv Neurol. 1984;40:489–95.PubMed
Becker JB. Direct effect of 17 beta-estradiol on striatum: sex differences in dopamine release. Synapse NY NY. 1990;5(2):157–64.CrossRef
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.CrossRef
- Sex steroids and schizophrenia
Reviews in Endocrine and Metabolic Disorders
Volume 13, Issue 3 , pp 187-207
- Cover Date
- Print ISSN
- Online ISSN
- Springer US
- Additional Links
- Gonadal hormones
- Sex differences
- Animal models
- Industry Sectors
- Julie A. Markham (1) (2)
- Author Affiliations
- 1. Maryland Psychiatric Research Center, University of Maryland-Baltimore School of Medicine, P.O. Box 21247, Baltimore, MD, 21228, USA
- 2. Maryland Psychiatric Research Center, Department of Psychiatry, and Program in Neuroscience, University of Maryland-Baltimore School of Medicine, Baltimore, MD, 21228, USA