Biological mechanisms whereby social exclusion may contribute to the etiology of psychosis: A narrative review

Selten, J-P., Booij, J., Buwalda, B. & Meyer-Lindenberg, A. Mar-2017 In : Schizophrenia Bulletin. 43, 2, p. 287-292 6 p.

Research output: Scientific - peer-reviewLiterature review

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  • Biological Mechanisms Whereby Social Exclusion May Contribute to the Etiology of Psychosis: A Narrative Review

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The purpose of this review is to examine whether a contribution of social exclusion to the pathogenesis of psychosis is compatible with the dopamine hypothesis and/or the neurodevelopmental hypothesis. Humans experience social exclusion as defeating. An animal model for defeat is the resident-intruder paradigm. The defeated animal shows evidence of an increased sensitivity to amphetamine, increased dopamine release in the nucleus accumbens and prefrontal cortex, and increased firing of dopaminergic neurons in the ventral tegmental area. As for humans, one study showed that amphetamine-induced striatal dopamine release was significantly greater among nonpsychotic young adults with severe hearing impairment than among normal hearing controls. Two other studies reported an association between childhood trauma and increased dopamine function in striatal subregions. Several studies have suggested that the perigenual anterior cingulate cortex (pgACC) may play a role in the processing of social stress. Importantly, the pgACC regulates the activity of the ventral striatum through bidirectional interconnections. We are not aware of studies in humans that examined whether (proxies for) social exclusion contributes to the structural brain changes present at psychosis onset. Animal studies, however, reported that long-term isolation may lead to reductions in volume of the total brain, hippocampus, or medial prefrontal cortex. Other animal studies reported that social defeat can reduce neurogenesis. In conclusion, the answer to the question as to whether there are plausible mechanisms whereby social exclusion can contribute to the pathogenesis of psychosis is cautiously affirmative.

Original languageEnglish
Pages (from-to)287-292
Number of pages6
JournalSchizophrenia Bulletin
Issue number2
StatePublished - Mar-2017


  • dopamine, neurodevelopment, social exclusion, social defeat, etiology, schizophrenia, psychosis, pathogenesis, ADULT HIPPOCAMPAL NEUROGENESIS, DEFEAT HYPOTHESIS, ENVIRONMENTAL RISK, CELL-PROLIFERATION, MENTAL-HEALTH, STRESS, SCHIZOPHRENIA, DOPAMINE, HUMANS, BRAIN

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