What risk factors tell us about the causes of schizophrenia and related psychoses.

Abstract

Genetic, epidemiologic, and molecular studies concur that liability to schizophrenia is transmitted through the inheritance of a number of genes of relatively small effect, some of which are shared with other psychoses. Each of these susceptibility genes causes minor deviations that are relatively innocent in themselves, for example, increased lateral ventricular volume, schizotypal personality, or subtle cognitive difficulties. However, when an individual is unlucky enough to inherit several of these traits, their cumulative effect, often compounded by environmental hazards, propels that person over a threshold for the expression of frank psychosis. Early environmental risk factors for schizophrenia include urban and winter birth, fetal malnutrition and hypoxia, and possibly prenatal viral infections; these early hazards have only a modest risk-increasing effect, and operate in the context of genetic risk. Preschizophrenic children are more likely to have minor psychomotor and cognitive problems; low IQ has a linear relationship with risk for schizophrenia. However, schizophrenia is not simply a neurodevelopmental disorder, because risk factors have been identified that have their effects proximal to the onset of psychosis: drug abuse, immigrant status, and social adversity and isolation. Both genetic and environmental risk factors appear to operate across diagnostic categories and therefore support a dimensional model of psychosis.