Catechol O-methyltransferase Val158Met Genotype and Neural Mechanisms Related to Affective Arousal and Regulation

邻苯二酚-O-甲基转移酶 心理学 前额叶皮质 功能磁共振成像 眶额皮质 神经科学 工作记忆 唤醒 多巴胺 精神病 扁桃形结构 认知 等位基因 精神科 遗传学 生物 基因
作者
Emily M. Drabant,Ahmad R. Hariri,Andreas Meyer‐Lindenberg,Karen E. Muñoz,Venkata S. Mattay,Bhaskar Kolachana,Michael Egan,Daniel R. Weinberger
出处
期刊:Archives of General Psychiatry [American Medical Association]
卷期号:63 (12) 被引量:378
标识
DOI:10.1001/archpsyc.63.12.1396
摘要

Catechol O-methyltransferase (COMT), the major enzyme determining cortical dopamine flux, has a common functional polymorphism (val(158)met) that affects prefrontal function and working memory capacity and has also been associated with anxiety and emotional dysregulation.To examine COMT val(158)met effects on corticolimbic circuitry reactivity and functional connectivity during processing of biologically salient stimuli, as well as the relationship to the temperamental trait of novelty seeking.Within-subject functional magnetic resonance imaging study.National Institute of Mental Health, Genes, Cognition, and Psychosis Program, Bethesda, Md. Patients One hundred one healthy subjects of both sexes.We found that the met allele was associated with a dose-dependent increase in hippocampal formation and ventrolateral prefrontal cortex activation during viewing of faces displaying negative emotion. In met/met homozygotes, limbic and prefrontal regions showed increased functional coupling. Moreover, in these same subjects, the magnitude of amygdala-orbitofrontal coupling was inversely correlated with novelty seeking, an index of temperamental inflexibility.Our results indicate that heritable variation in dopamine neurotransmission associated with the met allele of the COMT polymorphism results in heightened reactivity and connectivity in corticolimbic circuits. This may reflect a genetic predisposition for inflexible processing of affective stimuli, a mechanism possibly accounting for aspects of arousal and behavioral control that contribute to emotional dysregulation previously reported in met/met individuals.
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