Stress and neurodevelopmental processes in the emergence of psychosis

Abstract

The notion that stress plays a role in the etiology of psychotic disorders, especially schizophrenia, is longstanding. However, it is only in recent years that the potential neural mechanisms mediating this effect have come into sharper focus. The introduction of more sophisticated models of the interplay between psychosocial factors and brain function has expanded our opportunities for conceptualizing more detailed psychobiological models of stress in psychosis. Further, scientific advances in our understanding of adolescent brain development have shed light on a pivotal question that has challenged researchers; namely, why the first episode of psychosis typically occurs in late adolescence/young adulthood. In this paper, we begin by reviewing the evidence supporting associations between psychosocial stress and psychosis in diagnosed patients as well as individuals at clinical high risk for psychosis. We then discuss biological stress systems and examine changes that precede and follow psychosis onset. Next, research findings on structural and functional brain characteristics associated with psychosis are presented; these findings suggest that normal adolescent neuromaturational processes may go awry, thereby setting the stage for the emergence of psychotic syndromes. Finally, a model of neural mechanisms underlying the pathogenesis of psychosis is presented and directions for future research strategies are explored.

Keywords: ACTH; AST; BDNF; CHR; COMT; CRH; DA; DEX; DST; ESM; Experience Sampling Method; GHR; GRs; HPA; HVA; MRs; MTHFR; MZ; Met; N-methyl-d-aspartate; NAPLS; NMDA; NR1; North American Prodrome Longitudinal Study; OR; PCP; POMC; SAM; SIPS; SMST; Structured Interview for Prodromal Syndromes; Val; adrenocorticotrophic hormone; associative striatum; brain development; brain-derived neurotrophic factor; catechol-O-methyltransferase; clinical high risk; clinical high-risk; corticotrophin-releasing hormone; dexamethasone; dexamethasone suppression test; dopamine; genetic high risk; glucocorticoid receptors; homovanillic acid; hypothalamic–pituitary–adrenal; hypothalamic–pituitary–adrenal (HPA) axis; methionine; methylenetetrahydrofolate reductase; mineralocorticoid receptors; monozygotic; neuregulin 1; odds ratio; phencyclidine; pro-opiomelanocortin; prodrome; psychosis; sensorimotor striatum; stress; sympathetic–adrenal–medullary; valine.

Fig. 1

Stress and neurodevelopmental mechanisms in psychosis: hypothesized stages and processes.