Monoamine polygenic liability in health and cocaine dependence: imaging genetics study of aversive processing and associations with depression symptomatology.
Monoamine polygenic liability in health and cocaine dependence: imaging genetics study of aversive processing and associations with depression symptomatology.
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DOI：
10.1016/j.drugalcdep.2014.04.019
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发表时间：
2014-07-01
影响因子：
4.2
通讯作者：
Goldstein, Rita Z.
中科院分区：
文献类型：
--
作者：
Moeller, Scott. L.;Parvaz, Muhammad A.;Shumay, Elena;Wu, Salina;Beebe-Wang, Nicasia;Konova, Anna B.;Misyrlis, Michail;Alia-Klein, Nelly;Goldstein, Rita Z.
影响血清素信号的基因多态性调节对显著刺激的反应性和情绪障碍的风险。在这里，我们假设这些主要在抑郁症中探索的血清素基因也可能对药物成瘾有重要影响，有可能揭示药物症状、严重程度和/或可能的后遗症（如烦躁不安）的重要见解。利用成像遗传学方法，目前的研究在62名可卡因滥用者和57名健康对照者中测试了血清素转运体（5-HTTLPR）和单胺氧化酶A （MAOA）基因变异对厌恶信息处理的单独和联合影响。通过刺激显著性的心理生理标记（即事件相关电位的后期正电位（LPP）成分）来索引被动观看图像时对标准化不愉快图像的反应性。用贝克抑郁量表（BDI）评估抑郁症状。结果显示，与诊断无关，最不愉快的LPPs出现在MAOA-Low和至少一个5-HTTLPR“短”等位基因的个体中。在具有这两种风险变异的可卡因参与者中，不愉快的LPPs越高，BDI得分越高。综上所述，这些结果表明单胺信号的多位点遗传复合物通过与消极情绪体验相关的大脑功能与抑郁症症状有关。这项研究为未来的研究奠定了基础，可以调查药物成瘾和其他情绪失调的精神病理的临床结果和/或药物遗传疗法。
Gene polymorphisms that affect serotonin signaling modulate reactivity to salient stimuli and risk for emotional disturbances. Here, we hypothesized that these serotonin genes, which have been primarily explored in depressive disorders, could also have important implications for drug addiction, with the potential to reveal important insights into drug symptomatology, severity, and/or possible sequelae such as dysphoria. Using an imaging genetics approach, the current study tested in 62 cocaine abusers and 57 healthy controls the separate and combined effects of variations in the serotonin transporter (5-HTTLPR) and monoamine oxidase A (MAOA) genes on processing of aversive information. Reactivity to standardized unpleasant images was indexed by a psychophysiological marker of stimulus salience (i.e., the late positive potential (LPP) component of the event-related potential) during passive picture viewing. Depressive symptomatology was assessed with the Beck Depression Inventory (BDI). Results showed that, independent of diagnosis, the highest unpleasant LPPs emerged in individuals with MAOA-Low and at least one ‘Short’ allele of 5-HTTLPR. Uniquely in the cocaine participants with these two risk variants, higher unpleasant LPPs correlated with higher BDI scores. Taken together, these results suggest that a multilocus genetic composite of monoamine signaling relates to depression symptomatology through brain function associated with the experience of negative emotions. This research lays the groundwork for future studies that can investigate clinical outcomes and/or pharmacogenetic therapies in drug addiction and potentially other psychopathologies of emotion dysregulation.
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影响因子：
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作者：
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