The diagnosis of schizophrenia is usually made between ages 15 and 25.  During those 10 years, schizophrenia is diagnosed in 12 men to every 10 women (32). This may be because the onset of schizophrenia is delayed in women.  Many reasons for such a possibility have been considered: greater vulnerability of the male brain because of slower maturation (33), greater exposure to birth injury in males (34),  a neuroprotective effect of female hormones (35), less lateralization of the female brain (36), and greater exposure of males to head trauma (37).  It may be that men come to medical attention earlier than women because of the nature of their behavior when they are psychotic, or it may be that women with schizophrenia are initially misdiagnosed.

Narrow diagnostic criteria for schizophrenia exclude those whose initial episode is brief and affect laden (32), and these individuals are mainly women (38).

Earlier onset of schizophrenia (i.e., in men) usually means a more severe course of illness (39). On the other hand,  a delayed diagnosis (i.e.,  in women)  is a potential problem for treatment because long-lasting symptoms have been shown in prospective studies to be relatively nonresponsive to antipsychotic drugs (40,  41).  A schizophrenic illness initially diagnosed as depression or a bipolar disorder (i.e.,  in women)  means that antidepressants and mood stabilizers have preceded treatment with antipsychotics.  Such prior treatment can “prime” neural networks and result in an unanticipated antipsychotic response later (42).

Between ages 25 and 35,  equal numbers of men and women are diagnosed with schizophrenia (32).

After age 35,  a first visit to the psychiatrist is 50% more frequent in women with schizophrenia (32).

Very late onset of schizophrenia is also much more common in women than in men (43).  In other words, first-episode samples are composed of younger men and older women. It is, therefore, important to control for age when comparing results of drug response in women and men in first-episode studies.

Course of schizophrenia in women and men
Despite the possibility that their illness comes to treatment late, women with schizophrenia experience less severe symptoms,  fewer hospitalizations, shorter   admissions,  more   posthospitalization employment,  less trouble with the law,  and more intimate relationships than men with schizophrenia (30, 31). This has led to the conjecture that the response to antipsychotic drug treatment is more robust in women than in men (44). Superior outcome may have little to do with response to treatment and more with treatment adherence,  life style, social supports, the advantage of later onset, and relative hormonal protection (45,  46).  The corollary is that if women are doing better,  their maintenance antipsychotic doses need not be as high as those of men.

Schizophrenia mortality from unnatural factors (suicide, accident, homicide) is significantly higher in men than in women (47). As proportionately more seriously ill men in the schizophrenia population die, the levels of acuity between the two sexes begin to approximate, and indeed, in older age, the severity of illness is similar between the two sexes. This is true not only with respect to hospitalization variables such as the number and frequency of admissions and the lengths of stay but also with respect to mental status at follow-up, social adaptation, and occupational status. In older age, there may be less need for genderspecific prescribing (26, 48).

Mary V. Seeman, M.D.

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