Developmental neuropathology and the precursors of schizophrenia

Changes in the manifestation of vulnerability to schizophrenia across the l ifespan may hold important clues about aetiology. They may also illustrate some general principles about the nature of neurodevelopmental processes. W ithin the framework of a neural diathesis-stress model, we review findings on the precursors of schizophrenia and schizotypal personality disorder. Th e findings suggest that there are critical developmental periods for the ma nifestation of dysfunction and that, within certain domains of behaviour, t here is a temporal disjunction between the onset of the neuropathology and its expression. It also appears that the diathesis for schizophrenia involv es polymorphic behavioural expression, such that it can be manifested in mu ltiple domains - motoric, cognitive and socio-emotional. Taken together, th e data on the longitudinal course of schizophrenia indicate that the expres sion of the diathesis is moderated by central nervous system maturational p rocesses. One putative moderating system, the hypothalamic-pituitary-adrena l (HPA) axis, is discussed, and implications for preventive intervention ar e explored.