The question of whether schizophrenic-like disorders are neurodevelopmental or degenerative in origin has been argued since the time of Kraepelin. The authors provide evidence for the existence of two etiologically distinct endophenotypes of the psychoses contained within the rubric of familial non-affective psychosis (schizophrenia), one atrophic and the other neurodevelopmental. The atrophic psychosis, identified by progressive ventricular enlargement throughout adult illness, evidences progressive impairment of interests, relationships, and withdrawal from latency through adolescence, with emergence of trait-like negative symptoms which are only marginally responsive to conventional neuroleptics. This psychosis also exhibits delayed response of positive symptoms during neuroleptic treatment, and may also proceed to a praecox dementia in later life. In contrast, a putative neurodevelopmental psychosis, associated with static ventricles during the course of adult illness, also demonstrates preadolescent impairments, but impairments which do not progress to marked negative symptoms. Conventional neuroleptics appear to have little effect (except sedation) on positive symptoms, but appear to induce negative symptomatology and partial disengagement from the burden of persistent psychotic thought processes in such static ventricle psychoses. Thus, separate patterns of illnesses with different prodromal features, different treatment response patterns, and different patterns of residual (negative) symptoms appear to characterize patients with psychosis who have expanding as opposed to stable cerebral-ventricles at doses of neuroleptic at 10 mg haloperidol equivalents/day.
