The Stress Cascade and Schizophrenia: Etiology and Onset

Abstract

Psychosocial stress is included in most etiologic models of schizophrenia, frequently as a precipitating factor for psychosis in vulnerable individuals. Nonetheless, the stress-diathesis model has not been tested prospectively in prodromal patients as a predictor of psychosis. The biological effects of stress are mediated by the hypothalamic-pituitary-adrenal (HPA) axis, which governs the release of steroids, including cortisol. The past few decades have witnessed an increased understanding of the neural effects of stress and cortisol, including both normal and abnormal diatheses. As few biological markers have been evaluated as risk factors for psychosis in prodromal patients, the HPA axis and its interaction with intervening life events are apt candidates for study. In this article, we review the HPA axis and its neural effects, present a model for how stress might precipitate psychosis in vulnerable individuals, review the empirical evidence of a link between stress and schizophrenia symptoms, and propose a research design and appropriate statistical models to test the stress-diathesis model for psychosis onset in prodromal patients.

Abnormal Stress Responsivity in a Rodent Developmental Disruption Model of Schizophrenia

“…In particular, evidence suggests that early life stress is an important factor in the etiology of schizophrenia, a developmental disorder that typically manifests in adolescence or early adulthood. Stressful life events can precipitate or exacerbate the psychotic symptoms of schizophrenia (Corcoran et al, 2003;Meyer-Lindenberg and Tost, 2012) and psychosocial stressors increase the risk for developing the disease (Lim and Chong, 2009). It has been suggested that individuals who are at risk for schizophrenia are more susceptible to the effects of stress and that the interaction between a genetic or developmental predisposition and stress in early life could promote symptom onset (Benes, 1997;Tsuang, 2000;Walker et al, 2008).…”

Neurodevelopment, GABA System Dysfunction, and Schizophrenia

“…A third possible explanation is that environmental factors might predispose to altered trajectory of brain development, but individual genetic susceptibility defines the phenotype (and ultimately the diagnosis). We favor this last explanation (Horvath and Mirnics, 2014b), as MIA and immune system activation predispose to both autism and schizophrenia (Michel et al, 2012;Patterson, 2009), and early stress predisposes to a host of psychiatric disorders (Chrousos and Gold, 1992;Corcoran et al, 2003;O'Donnell, 2012;Walker et al, 2008). However, symptoms of autism emerge very early in life while schizophrenia onset is typically during late adolescence or early adulthood.…”

Service attachment: The relative contributions of ward climate perceptions and attachment anxiety and avoidance in male inpatients with psychosis

“…Previous research has shown that the psychosocial environment may have a negative influence on the course o f schizophrenia, particularly on acute wards (Concoran et al, 2003;, where patients experience many relationships (Forster et ah, 2003), there is a high staff turnover , and staff work many different shifts . Conversely, a supportive ward environment is considered by many as a precondition for successful treatment (Schalast, Redies, Collins, Stacey & Howells, 2008) and research has highlighted that situational stressors that exacerbate symptoms of schizophrenia can be lessened through a supportive environment .…”