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Neurohormones, Neurodevelopment, and Psychosis 265with schizophrenia during the modal risk period, early adulthood, manifest agradual deterioration in function that begins in early adolescence (Neumann &Walker, 1995). These findings suggest that postpubertal neurodevelopmental processesinteract with the expression of vulnerability.Research on diagnosed patients has shown that a variety of both structural andfunctional brain abnormalities are linked with psychotic disorders, indicating thatmultiple neural systems are affected. One or more of these neural abnormalitiesmay be critical for the emergence of psychotic symptoms in adolescence/youngadulthood, whereas other neural systems are likely to play a modulating role inthe expression of dysfunction in key systems. Further, as stated above, there isstrong evidence that maturational changes are playing a role in the expression ofthe basic neuropathology and, as a consequence, the clinical manifestations.It has been suggested that the neural systems governing the response to stress,especially the hypothalamic-pituitary-adrenal (HPA) axis, may function to augmentthe expression of the core vulnerability to psychosis (Cunningham, Bhattacharayya,& Benes, 2002; Walker & Diforio, 1997). In this chapter, we briefly review researchfindings that bear on adolescent vulnerability for psychosis and neurodevelopmentof the HPA-hippocampal system, with an emphasis on implications for preventiveintervention. (We use the general term psychosis, rather than schizophrenia, becauseof evidence that the same neural mechanisms are implicated in most forms of psychosis).The working model posits that the HPA-hippocampal system moderatesthe expression of constitutional vulnerability for psychosis, and assumes that adolescenceis a critical period for this effect because postpubertal neurodevelopmentof the HPA axis and hippocampus increases susceptibility to the adverse effects ofstress-induced glucocorticoid secretion, and because hormonal changes during thisperiod can trigger latent genetic vulnerabilities.Finally, because the rate of psychotropic medication of adolescents has risensharply in recent years, it is now possible to examine their biobehavioral consequencesfor development (Zito et al., 2003). We present preliminary data from ourrecent research that suggests how psychopharmacologic interventions might alterHPA function, and thereby modify the transition to psychosis in at-risk adolescents.The HPA AxisThe HPA axis is a neural system that is sensitive to environmental challenges andis activated in response to physical and psychological factors that threaten homeostasis(Charmandari, Kino, Souvatzoglou, & Chrousos, 2003; Dorn & Chrousos,1997). The initial step in the neurohormonal cascade of the HPA axis is the releaseof the hypothalamic hormone, corticotropin releasing hormone (CRH). This, in turn,triggers the release of adrenocorticotropin (ACTH) from the anterior pituitary. ACTHthen acts on the adrenal glands, leading to the release of glucocorticoids (cortisol