Adult-onset schizophrenia is preceded in childhood by mild neuromotor, cognitive, and behavioral anomalies that occur with the same frequency in boys and girls during early childhood. But from school age on, behavioral anomalies in children who later go on to develop schizophrenia appear to be more severe, and to be more frequent in boys than in girls. Boys exhibit more hyperactivity, physical and verbal aggression, and failure of behavioral inhibition, whereas girls exhibit more shyness, social withdrawal, depession, and anxiety. This is not specific to those predisposed to schizophrenia but reflects childhood development in general: little behavioral sex difference initially, but, by late childhood, more evidence of externalizing behaviors and attention deficits in boys and more anxiety in girls.

Prodrome
Girls who later develop schizophrenia, as a group, are apt to be shy, reserved, insecure, and relatively isolated. In contrast, boys who later develop schizophrenia tend toward irritability and defiance. Men with schizophrenia have consistently reported more premorbid deficits in social and occupational functioning than do women with schizophrenia. The precipitants to full-blown illness also differ between the sexes. In boys, illness is frequently triggered by substance abuse or head trauma; in girls, common antecedents include social isolation and childbirth.

Age of Onset
In Germany, Hafner (2005) showed that boys develop schizophrenia 3–4 years earlier than do girls. This finding has been replicated around the world, although a few studies have found no difference.

The onset distribution across the lifecycle differs in men and women. The peak age of onset in males is between 21 and 25 years, whereas the peak age in females ranges from 25 to 30 years. More men first become ill in late adolescence; women show a second peak of incidence around menopause. Women have a two to three times greater relative risk of developing late-onset (after age 45) schizophrenia. In familial cases, however, age-of-onset gender differences are not significant. Women with a family history first become ill at the same mean age as do men.

The difference in age at onset between familial and nonfamilial schizophrenia (older onset age in nonfamilial cases) is significantly greater in women than in men, suggesting that the effect of genetic loading on onset age overcomes what has been described as women’s natural “neuroprotection” against adolescent breakdown.

Women’s later onset age in nonfamilial schizophrenia holds true for all definitions of onset: the first sign of any disorder, the first negative symptom, and the first positive symptom. All these milestones differ by 3–4 years between men and women and are not, as far as can be ascertained, attributable to gender-specific delays in seeking help.

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  »  » Brain Abnormalities - Schizophrenia and Gender

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MARY V. SEEMAN
Mary V. Seeman, MDCM, FRCPC, FACP, is Professor and Tapscott Chair of Schizophrenia Studies at the University of Toronto and Centre for Addiction and Mental Health,Toronto, Ontario, Canada.

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REFERENCES

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2. Angermeyer, M. C., Kuhn, L., & Goldstein, J. M. (1990). Gender and the course of schizophrenia: Differences in treated outcomes. Schizophrenia Bulletin, 16, 293–307.
3. Cho, J. J., Iannucci, F. A., Fraile, M., Franco, J., Alesius, T. N., & Stefano, G. B. (2003). The role of the estrogen in neuroprotection: Implications for neurodegenerative diseases. Neuroendocrinology Letters, 24, 141–147.
4. Goldstein, J. M., Seidmann, L. J., O’Brien, L. M., Horton, N. J., Kennedy, D. N., Makris, H., et al. (2002). Impact of normal sexual dimorphisms on sex differences in structural brain abnormalities in schizophrenia assessed by magnetic resonance imaging. Archives of General Psychiatry, 15, 154–164.

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