Age and Gender as Risk Factors

Age and level of social development are highly significantly correlated. Men fall ill with schizophrenia 3 to 4 years earlier and, in our population of origin, married 2.5 years later than women. Their level of social development at illness onset, in the social role of marriage in particular, was therefore considerably lower than that of women. In addition, young men with schizophrenia showed a significant excess of socially adverse behaviour at first admission, e.g. self-neglect, lack of interest in finding a job, deficits in hygiene, aggressive behaviour and an elevated lifetime prevalence of alcohol and drug abuse until first admission. Female patients in contrast showed a significant excess of ''social conformity'', which presumably reflects a different type of adaptive behaviour. The socially adverse behaviour of young males has been confirmed in many population studies by elevated rates of conduct disorders, aggressiveness, antisocial personality, and alcohol and drug abuse [117,118]. In schizophrenia it must therefore be classified as gender-specific illness behaviour and not as a direct expression of the disorder [18].

The more favourable social course of the disorder observed in pre-menopausal women has to do with their higher level of social development in our culture as a result of a later illness onset and socially more adaptive illness behaviour. It does not appear to be related to women having a milder form of the disorder.

In a stepwise logistic regression [119], the level of social development at the first psychotic symptom and the socially adverse behaviour at the end of the prephase turned out to be the only factors significantly predicting five-year social outcome. The traditional prognostic indicators - age, gender, symptomatology and type of illness onset - merely had indirect effects via the level of social development at illness onset and illness behaviour. The symptom-related illness course showed no sex difference. It seems that the social course of schizophrenia is largely determined by social status or development at illness onset as well as the functional impairment and social disability that emerge in the early illness course. In early-onset illness, the consequence is social stagnation at a low level of social development; in late-onset illness, when a comparatively high level of social development has been attained, the consequence is social decline [62].

The earlier onset of schizophrenia in men has been widely reported (for review, see 120-122). The difference is not an artefact due to gender differences in diagnostic definitions and procedures, help-seeking behaviour or in the length of the early illness course [123-126]. An analysis of pooled data from 10 centres of the World Health Organization (WHO) Determinants of Outcome of Severe Mental Disorders (DOSMED) study [127] showed a mean difference of 3.4 years and some consistency across countries and cultures.

No such gender difference in age at onset is shown by siblings and twins [128,129], and this is almost exclusively because of women's reduced age of onset. Studying the ABC first-episode sample, Konnecke et al. [130] found that two risk factors for schizophrenia (at least one first-degree relative with schizophrenia and pre- and perinatal complications) significantly reduced the gender difference in age at onset by significantly lowering the age of onset in women, but not in men. When neither risk factor was present, the mean age of onset in women was 4.9 years later than in men. Underlying the protective effect of oestrogen that delays illness onset, there seems to be an antagonistic balance between the sex hormone and strength of predisposition to illness. The delaying effect of oestrogen on illness onset is the strongest in cases who have the weakest predisposition to illness or lack the two risk factors.

The duration of the prodromal stage does not differ significantly between the sexes or in five-year age groups over an age range of 12 to 59 years, apart from a slightly shorter duration in early-onset illness. Male onsets peak at 15 to 24 years, female onsets at age 15 to 29 years. Because of decreasing oestrogen secretion with age, women aged 45 to 50 years show a second peak of onsets lower than the first one. The second peak has also been demonstrated on pooled data from the WHO DOSMED study [127] and in the Camberwell case-register population [126]. The explanation of these sex differences by a protective effect of oestrogen [125,131] was supported in animal experiments by the attenuating effect that a four-week oestrogen treatment had on apomorphine-stimulated dopaminergic behaviour as a result of sensitivity reduction in central D2 receptors [132,133].

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