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.

Beyond “Cold” Cognition: Exploring Cognitive Control of Emotion as a Risk Factor for Psychosis

“…Similarly, it is possible that successful development of cognitive control of emotion mechanisms and accompanying adaptive ER strategies during adolescence is one factor that distinguishes individuals who remit from the high-risk state from those who continue to meet CHR criteria. This is consistent with the neurodevelopmental theory of psychosis [113]; however, prospective longitudinal studies examining cognitive control of emotion in the context of neural and social development over the course of adolescence in high-risk samples are needed in order to answer this question.…”

What causes psychosis? An umbrella review of risk and protective factors

“…In fact, the effect of both factors on the risk of developing psychotic disorders may be explained (mediated) by environmental exposures at an individual level, such as substance use, social isolation, social defeat, social fragmentation, and discrimination 124 . Interestingly, many of these exposures appear to share a common factor of social stress and defeat 125,126 , and have beenmostly indirectly -associated with various neurobiological sequelae of potential relevance to psychotic disorders 127 , such as alterations in the hypothalamic-pituitary-adrenal axis 128,129 , inflammation 130 , altered brain functioning 131,132 , reduced brain volumes 133 , and neurochemical dysfunctions 126,134,135 . However, studies to directly assess the correlations between these factors k -number of samples for each factor, ES -effect size, N -number of cases, PI -prediction interval, CI -confidence interval, SSE -small-study effect, ESBexcess significance bias, LS -largest study with significant effect, eOR -equivalent odds ratio, CE -class of evidence, IRR -incidence rate ratio, OR -odds ratio, k -number of samples for each factor, ES -effect size, N -number of cases, PI -prediction interval, CI -confidence interval, SSE -small-study effect, ESBexcess significance bias, LS -largest study with significant effect, eOR -equivalent odds ratio, CE -class of evidence, IRR -incidence rate ratio, OR -odds ratio, RR -relative risk, Ig -immunoglobulin, NA -not assessable, ns -not significant 133,136 .…”

The role of stress‐regulation genes in moderating the association of stress and daily‐life psychotic experiences

“…In this sense, a limited but increasing number of GxE studies have shown that certain single nucleotide polymorphisms (SNPs) interact with distal or proximal stress to heighten risk for psychotic experiences (PEs; e.g., 11). For example, it has been shown that the brain‐derived neurotrophic factor ( BDNF ) Val66Met polymorphism moderates the psychosis‐inducing effects of distal 12, 13 and momentary stress 14.…”