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  • Increased release of dopamine in the striata of young adults with hearing impairment and its relevance for the social defeat hypothesis of schizophrenia.

Increased release of dopamine in the striata of young adults with hearing impairment and its relevance for the social defeat hypothesis of schizophrenia.

JAMA psychiatry (2014-10-02)
Martin Gevonden, Jan Booij, Wim van den Brink, Dennis Heijtel, Jim van Os, Jean-Paul Selten
摘要

An increased risk for psychosis is observed in people with hearing impairment. According to the social defeat hypothesis, the long-term experience of exclusion leads to enhanced baseline activity and/or sensitization of the dopamine system and puts the individual at increased risk for psychosis. To investigate whether young adults with severe hearing impairment (SHI) experience more feelings of social defeat, show greater dopamine release in response to dexamphetamine, and report a stronger subjective reaction to this substance than normal-hearing young adults and to examine whether dopamine release is associated with both self-reported social exclusion and dexamphetamine-induced psychotic experiences. A sample of 19 participants with SHI and 19 smoking-, age-, and sex-matched healthy controls underwent single-photon emission computed tomography with iodine 123-labeled iodobenzamide as a radiotracer before and after an amphetamine challenge at an academic hospital. Dexamphetamine sulfate (0.3 mg/kg) administered intravenously. Baseline D2/3 receptor binding and endogenous dopamine release. The participants with SHI reported experiencing more feelings of social defeat (U=109, z=-2.09, P=.04) and loneliness (U=87.5, z=-2.72, P=<.001) than did healthy controls, but they did not differ from healthy controls with regard to baseline psychotic symptoms (U=156.5, z=-0.70, P=.48). There were no significant group differences in baseline D2/3 receptor binding. However, repeated-measures multivariate analysis of covariance with age (in months) and tobacco smoking (in pack-years) as covariates showed that there was a greater amphetamine-induced striatal dopamine release among the participants with SHI than among the healthy controls (F1,34=4.55, P=.04). After amphetamine administration, the participants with SHI reported more changes in affect than the healthy controls, but not a greater increase in psychotic symptoms. Likewise, reports of social exclusion and an increase in psychotic symptoms were not associated with dopamine release. Our study presents preliminary evidence of dopamine sensitization in a socially excluded group of people with hearing impairment. If replicated by future studies in other excluded groups, this finding may have major implications for our understanding of the underlying mechanism and for prevention of psychotic disorders.

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Sigma-Aldrich
盐酸多巴胺 盐酸盐
Sigma-Aldrich
氢化可的松 溶液, 50 μM, sterile-filtered, BioXtra, suitable for cell culture
Supelco
皮质醇标准液 溶液, 1.0 mg/mL in methanol, ampule of 1 mL, certified reference material, Cerilliant®
Supelco
盐酸多巴胺 盐酸盐, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
多巴胺盐酸盐标准液 CRM 盐酸盐 溶液, 1.0 mg/mL in methanol with 5% 1 M HCl (as free base), ampule of 1 mL, certified reference material, Cerilliant®
盐酸多巴胺 盐酸盐, European Pharmacopoeia (EP) Reference Standard