From Onset and Prodromal Stage to a Life-Long Course of Schizophrenia and Its Symptom Dimensions: How Sex, Age, and Other Risk Factors Influence Incidence and Course of Illness

Abstract

The core symptoms of psychosis-delusions, hallucinations, and thought disorders-are not unique to the disorder traditionally called schizophrenia. They occur at the early stages of various brain diseases, too. Psychosis seems to be a preformed pattern of response of the human brain. Most schizophrenia onsets are marked by a prodromal stage extending over several years and producing the maximum of social consequences. Schizophrenia incidence shows a steep increase culminating at age 15 to 25 years in males. In females it reaches a first peak at age 15 to 30 years and a second, flatter peak at menopausal age (44-49 years). Thereafter, incidence declines to a plateau at later ages. Unlike what the findings of most large-scale epidemiological studies applying an upper age limit of 45 to 55 years suggest, schizophrenia is a disorder of all ages. The lifetime risk seems to be the same for both sexes. The lower incidence in premenopausal women is accounted for by the downregulating effect of oestrogen on dopamine receptors. This hormonal protective effect is antagonised by the genetic effect of a high familial load. In the long-term illness course, right-censored to 11.2 years following first admission, the number of psychotic relapse episodes ranges from 0 to 29 with a mean of 3. The positive symptom dimension produces the highest number of relapses and the shortest duration of exacerbations with a mean length of two months. The depressive and negative symptom dimensions show exacerbations extending over nearly six months on average. Following the first illness episode symptom scores decline sharply, reaching a plateau five years after first admission. Negative symptoms come to a plateau after 2 to 3 years in females and after 5 years in males. Depression is the most frequent type of symptom in the long-term course. In the light of these results urgent treatment issues will be discussed.

Figure 1

Mean age by 5 definitions of onset until first admission; ABC first-episode sample of broadly defined schizophrenia (N=232). Source: [8], modified.

Figure 2

Left: ABC Schizophrenia Study: age at onset of schizophrenia (ICD-9: 295, 297, 298.3, 298.4) (first psychotic symptom) by sex; right: population-based first-admission rates for schizophrenia (ICD-8: 295) in Denmark 1976 by age and sex. Source: [9].

Figure 3

WHO Determinants of Outcome Study: mean ages at onset in the centres and the total sample (N=1,292). Source: [12].

Figure 4

Distribution of age at onset of schizophrenia (first-ever sign of mental disorder) by sex; ICD 9-295, 297, 298.3, 298.4 (ABC Schizophrenia Study). Source: [25].

Figure 5

Annual first-contact rates for nonaffective psychoses in the elderly population (>60 years); based on case-register data. Source: [32], modified.

Figure 6

Psychotic symptoms showing significant age trends; based on data from CIMH (N=1,109) (CIMH: Central Institute of Mental Health). Source: [33].

Figure 7

Age at first psychotic symptom by gender and familial load; ABC first-episode sample of schizophrenia (N=232). Source: [51].

Figure 8

Social course of schizophrenia as based on economic independence (smoothened curves) in the early and medium-term illness course in three groups of patients aged 12-20, 21-35, and 36-59 years at inclusion in study (= first admission), ABC follow-up sample (n=115). Source: [60], modified.

Figure 9

Marriage or stable partnership. Source: [61].