Developmental trajectory and disease progression in schizophrenia: The conundrum, and insights from a 12-year prospective study in the Monaghan 101

Though conceptualised originally as a deteriorating disorder, some contemporary studies have been interpreted as challenging these foundations; more radically, it has been proposed that schizophrenia may be a 'static encephalopathy' of neurodevelopmental origin. The argument offered here is that schizophrenia is indeed a neurodevelopmental disorder, but that this is not in itself antithetical to later disease progression. Rather, the onset of psychosis may reflect the maturationally-mediated triggering of an active disease process that is associated with progressive deterioration unless attenuated by antipsychotic drugs. A developmental trajectory is proposed to link first or early second trimester dysplasia to the chronic course of the illness; from this, it is argued that schizophrenia is inherently a progressive disorder but that antipsychotic drugs may act to ameliorate this progressive component and thus confer on the disease course some of the characteristics of a 'static encephalopathy'. The 'true' natural history of an illness cannot be determined from studies in treated populations.