Brain Abnormalities - Schizophrenia and Gender

On magnetic resonance imaging (MRI) scans, reduced cortical brain areas, small left hippocampal formations, and enlarged lateral ventricles are present more often in male than in female patients with schizophrenia. There may also be sex differences within the affected brain areas. Compared to men, women with schizophrenia have better preserved gray matter in the hippocampus, frontal cortex, caudate nucleus, and temporal gyrus—all regions involved in higher functions such as thinking, attention, language, and working memory. But women’s brains show more gliosis and focal damage in the brain areas associated with emotional processing.

Neuropsychological differences
Although social cognition is more impaired in men than in women with schizophrenia, it is not clear whether other cognitive deficits are more pronounced in one sex than in the other.

Self-neglect, reduced interest in a job, social withdrawal, and deficits of communication occur significantly more frequently in men than in women at first presentation. The prevalence of drug and alcohol abuse is significantly higher in men. Women in the general population (and also women with schizophrenia) compared to men show more emotional reactivity to the stresses of everyday life. They also have higher rates of positive psychotic symptoms (delusions and hallucinations). These findings agree with what is known about the role of emotional processes in the cognitive biases that lead to positive symptoms.

Negative emotional states may contribute to a “psychotic” appraisal of experience, thus provoking psychotic symptoms.  Higher levels of depression,  such as those found in women with schizophrenia compared to men, may induce biases in logical reasoning that contribute to positive symptoms.

Course and outcome trajectory of illness in men and women
Men have a poorer short- and medium-term course of schizophrenia than do women.

This is true whether one looks at relapse rate, rehospitalization, time to relapse, duration of hospital admission, response to treatment, or social adjustment and occupational functioning. Prison rates and suicide rates are also lower in women. In a review of short- (2–5 years)  and medium-  (5–10 years)  term follow-up studies,  Angermeyer,  Kuhn,  and Goldstein (1990) found that about half of the studies indicated a more favorable outcome in women. The other half found no sex differences. It is the social course of the illness, rather than symptom scores, that is significantly associated with gender. Women’s general tendencies toward prosocial behavior, cooperativeness, and compliance might be a key influence here. Long-term prognosis (13–40 years), however, appears to be the same for women and men. The improved earlier course for women is perhaps a result of a later start to their illness; the seeming deterioration after menopause may be secondary to the loss of the neuroprotective effects of estrogens or to the problems that women generally experience when they grow old: loneliness, poverty, age-related health problems, loss of social supports.


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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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