CLINICAL HANDBOOK OF SCHIZOPHRENIA

576 VIII. SPECIAL TOPICSwhereas adolescent substance abuse, particularly cannabis, is more prevalent in thepremorbid histories of males.Because the pace of cerebral development is slower in males than in females, the malefetal brain is considered more susceptible to environmental adversity than the female brain,due at least in part to estrogen. By activating common intracellular signaling pathways andinitiating “cross-talk” with neurotrophins, the female hormone estrogen is known to playan influential role in promoting neuronal survival after environmental insult. More symmetricalbrain organization in females is also considered protective, in that the other side ofa symmetrical brain can compensate for functions unilaterally disrupted. During adolescence,sex-specific (hormonally induced?) reductions in synaptic density may additionallycontribute to the extra vulnerability of the male brain at that critical time.INCIDENCE RATESRecent meta-analyses of incidence risk report a mean ratio of 1.42 for men over women, anexcess for males that is only slightly reduced when studies of lower quality are excluded.This sex difference in incidence is significantly smaller in studies conducted prior to 1980.This suggests that the broader diagnoses prevalent before 1980 (at that time, the diagnosisof schizophrenia would have included schizoaffective disorder and perhaps bipolar disorderwith psychotic features) tended to flatten the sex ratio. No significant sex differences inincidence have been reported in studies from developing countries. The high death rate ofvulnerable children and adolescents in developing countries might offer a partial explanation.Because more women than men first become ill with schizophrenia after age 55 (thefrequent cutoff age for epidemiological studies), these older women may be lost to incidenceanalysis. But studies with an age cutoff of 64 years or older also yield a higher mean risk ratiofor men (1.32). On the other hand, no sex differences have been found in prevalence ratesof schizophrenia (whether point, period, lifetime, or lifetime morbid risk prevalences). Thediscrepancy between incidence and prevalence sex ratios could be accounted for by bettermale recovery (doubtful), higher rates of male incarceration (i.e., epidemiological unavailability)or higher male death rates, particularly from suicide.CHILDHOOD DEVELOPMENTAdult-onset schizophrenia is preceded in childhood by mild neuromotor, cognitive, andbehavioral anomalies that occur with the same frequency in boys and girls during earlychildhood. But from school age on, behavioral anomalies in children who later go on todevelop schizophrenia appear to be more severe, and to be more frequent in boys than ingirls. Boys exhibit more hyperactivity, physical and verbal aggression, and failure of behavioralinhibition, whereas girls exhibit more shyness, social withdrawal, depession, andanxiety. This is not specific to those predisposed to schizophrenia but reflects childhooddevelopment in general: little behavioral sex difference initially, but, by late childhood,more evidence of externalizing behaviors and attention deficits in boys and more anxietyin girls.PRODROMEGirls 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