Developmental neuropathology and the precursors of schizophrenia.

Changes in the manifestation of vulnerability to schizophrenia across the lifespan may hold important clues about aetiology. They may also illustrate some general principles about the nature of neurodevelopmental processes. Within the framework of a neural diathesis-stress model, we review findings on the precursors of schizophrenia and schizotypal personality disorder. The findings suggest that there are critical developmental periods for the manifestation of dysfunction and that, within certain domains of behaviour, there is a temporal disjunction between the onset of the neuropathology and its expression. It also appears that the diathesis for schizophrenia involves polymorphic behavioural expression, such that it can be manifested in multiple domains - motoric, cognitive and socio-emotional. Taken together, the data on the longitudinal course of schizophrenia indicate that the expression of the diathesis is moderated by central nervous system maturational processes. One putative moderating system, the hypothalamic-pituitary-adrenal (HPA) axis, is discussed, and implications for preventive intervention are explored.