First onset and early symptomatology of schizophrenia. A chapter of epidemiological and neurobiological research into age and sex differences.

In the frame of the ABC (Age, Beginning and Course) Schizophrenia Project we studied the influence of age and sex on first-ever onset, symptom manifestation and early course up to first admission in schizophrenia by using a large, representative sample of first-admitted schizophrenic patients. The results showed that the two variables had surprisingly little bearing upon the core symptoms, particularly on negative and other most frequent symptoms and on first-rank symptoms. In 70% of the cases schizophrenia started solely with negative symptoms, in 20% with negative and positive and in 10% with positive symptoms only. In most of the cases symptoms accumulated exponentially up to the first acute episode with positive symptoms appearing considerably later. The age differences observed concerned secondary phenomena associated with developmental factors. Such phenomena, i.e. anxiety, depression and the cognitive formation of delusions, can be interpreted as responses to the psychosis. Also the sex differences, which culminated in far more frequent socially negative disease behaviour in males, were limited to secondary phenomena. This positive and negative core symptomatology of schizophrenia seems to be astonishingly uniform and fairly independent of age and sex at this early stage of the disease. The only remarkable difference was a three to four years higher mean age of onset in females. We were able to show in animal experiments and to confirm in a clinical study that this finding is attributable to a neuromodulatory effect of estrogens on the sensitivity of D2 receptors in the brain. Apparently, estrogens raise the vulnerability threshold until menopause and have a slight neuroleptic-like effect on the symptomatology in acute schizophrenic episodes.