There is a substantive literature on the behavioral effects of psychosocial stressors on schizophrenia. More recently, research has been conducted on neurohormonal indicators of stress responsivity, particularly cortisol release resulting from activation of the hypothalamic-pituitary-adrenal (HPA) axis. This article integrates the psychosocial and biological literatures on stress in schizophrenia, and it offers specific hypotheses about the neural mechanisms involved in the effects of stressors on the diathesis. Both the behavioral and biological data indicate that stress worsens symptoms and that the diathesis is associated with a heightened response to stressors. A neural mechanism for these phenomena is suggested by the augmenting effect of the HPA axis on dopamine (DA) synthesis and receptors. Assuming the diathesis for schizophrenia involves an abnormality in DA receptors, it is proposed that the HPA axis acts as a potentiating system by means of its effects on DA. At the same time, DA receptor abnormality and hippocampal damage render the patient hypersensitive to stress. This neural diathesis-stress model is consistent with findings on prenatal factors and brain abnormalities in schizophrenia, and it provides a framework for explaining some key features of the developmental course and clinical presentation.

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Changes in the manifestation of vulnerability to schizophrenia across the life‐span 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.

The observations of family members as well as the results of past research suggest that a variety of developmental pathways can precede the onset of schizophrenia in early adulthood. In this article, we describe recent findings from our research on the childhood precursors of schizophrenia. Taken together, the results indicate that childhood behavioral, emotional, and motoric dysfunction occur at a higher rate in preschizophrenia subjects when compared to control subjects. Further, there are developmental changes as well as significant variability among schizophrenia patients in the nature and severity of childhood impairment. Drawing on the prevailing diathesis-stress model, we explore the moderating role that stress exposure and reactivity may play in the expression of the organic diathesis for schizophrenia. Specifically, we consider the role of the biological stress response in the production of developmental changes and individual differences in the pathways to schizophrenia. Given extant models of dopamine involvement in the neuropathology of schizophrenia, stress-induced Cortisol release may alter the expression of subcortical abnormalities in dopamine neurotransmission. Thus, we present a neural mechanism for the hypothesized behavioral sensitivity to stress exposure in schizophrenia, and explore the capacity of the model to account for the changing behavioral manifestations of vulnerability.

I the assumption that the behavioral expression of the diathesis is moderated by various exogenous and endogenous factors (Cannon et al., 1994;Fowles, 1992; Walker 8r Diforio, 1997;Zubin & Spring, 1977). The identification of these moderators has been of primary interest to many investigators in the field. Among the exogenous factors that have been the focus of research attention are psychosocial stress and obstetrical insults. Potential endogenous moderating factors include cognitive abilities and central nervous system maturation.It has been shown that the onset of schizophrenia is often preceded by childhood adjustment problems and that the severity of these problems increases with age (Neumann, Grimes, Walker, & Baum, 1995). It has long been assumed that the prodromal phase begins in adolescence for many patients; the above studies document a particularly marked increase in interpersonal deficits and ideational abnormalities with the onset of puberty. These findings are consistent with the assumption that the behavioral expression of the diathesis is moderated by maturational processes.In this chapter, we focus on the developmental trajectory of 469