Psychosocial Stress and Psychosis. A Review of the Neurobiological Mechanisms and the Evidence for Gene-Stress Interaction

• Published in: Schizophrenia bulletin Vol. 34; no. 6; pp. 1095 - 1105
• Main Authors: van Winkel, Ruud, Stefanis, Nicholas C., Myin-Germeys, Inez
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.11.2008; Oxford Publishing Limited (England)
• Subjects: Adult; Alleles; Animals; Brain - physiopathology; Brain-Derived Neurotrophic Factor - genetics; Catechol O-Methyltransferase - genetics; Child; Disease Models, Animal; Dopamine - physiology; Gene Expression - genetics; Genetic Predisposition to Disease - genetics; Genetic Predisposition to Disease - psychology; Humans; Hypothalamo-Hypophyseal System - physiopathology; Pituitary-Adrenal System - physiopathology; Psychosis; Risk Factors; Schizophrenia - genetics; Schizophrenia - physiopathology; Schizophrenic Psychology; Serotonin Plasma Membrane Transport Proteins - genetics; Social Environment; Stress, Psychological - complications; Stress, Psychological - physiopathology; Theme: Schizophrenia Aetiology: From G to GxE Guest Editor: Jim van Os and Robin Murray; trauma; ethnicity; urbanicity; gene-environment interaction; cannabis; schizophrenia; sensitization
• ISSN: 0586-7614; 1745-1701
• DOI: 10.1093/schbul/sbn101

This article presents evidence suggesting that psychosocial stress may increase risk for psychosis, especially in the case of cumulative exposure. A heuristically useful framework to study the underlying mechanisms is the concept of "behavioral sensitization" that stipulates that exposure to psychosocial stress-such as life events, childhood trauma, or discriminatory experiences-may progressively increase the behavioral and biological response to subsequent exposures. The neurobiological substrate of sensitization may involve dysregulation of the hypothalamus-pituitary-adrenal axis, contributing to a hypothesized final common pathway of dopamine sensitization in mesolimbic areas and increased stress-induced striatal dopamine release. It is argued that, in order to reconcile genetic and environmental influences on the development of psychosis, gene-environment interactions may be an important mechanism in explaining between-subject differences in risk following (cumulative) exposure to psychosocial stress. To date, most studies suggestive of gene-stress interaction have used proxy measures for genetic vulnerability such as a family history of psychosis; studies investigating interactions between molecular genetic measures and psychosocial stressors are still relatively scarce. Preliminary evidence suggests that polymorphisms within the catechol-O-methyltransferase and brain-derived neurotrophic factor genes may interact with psychosocial stress in the development of psychosis; however, extensive further investigations are required to confirm this.