Psychosocial stress and psychosis. A review of the neurobiological mechanisms and the evidence for gene-stress interaction.
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.
van Winkel
Ruud
R
Department of Psychiatry and Neuropsychology, EURON, South Limburg Mental Health Research and Teaching Network, Maastricht University Medical Centre, Maastricht, The Netherlands. ruud.vanwinkel@sp.unimaas.nl
Stefanis
Nicholas C
NC
Myin-Germeys
Inez
I
D000328:Adult; D000483:Alleles; D000818:Animals; D001921:Brain / Q000503:physiopathology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D002394:Catechol O-Methyltransferase / Q000235:genetics; D002648:Child; D004195:Disease Models, Animal; D004298:Dopamine / Q000502:physiology; D015870:Gene Expression / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics / Q000523:psychology; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D012307:Risk Factors; D012559:Schizophrenia / Q000235:genetics* / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D012931:Social Environment; D013315:Stress, Psychological / Q000150:complications* / Q000503:physiopathology
D019208:Brain-Derived Neurotrophic Factor; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D002394:Catechol O-Methyltransferase; D004298:Dopamine