Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Square J5, D-68159 Mannheim, Germany.
Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Square J5, D-68159 Mannheim, Germany.
Eur Neuropsychopharmacol. 2015 Aug;25(8):1128-35. doi: 10.1016/j.euroneuro.2015.04.013. Epub 2015 Apr 18.
The endogenous opioid system is involved in the pathophysiology of alcohol-use disorders. Genetic variants of the opioid system alter neural and behavioral responses to alcohol. In particular, a single nucleotide polymorphism rs1799971 (A118G) in the mu-opioid receptor gene (OPRM1) is suggested to modulate alcohol-related phenotypes and neural response in the mesocorticolimbic dopaminergic system. Little is known about the clinical implications of these changes. The current study investigated the relationship of genotype effects on subjective and neural responses to alcohol cues and relapse in a sample of abstinent alcohol-dependent patients. Functional magnetic resonance imaging (fMRI) was used to investigate alcohol cue-reactivity and drinking outcome of 81 abstinent alcohol-dependent patients. G-allele carriers displayed increased fMRI cue-reactivity in the left dorsal striatum and bilateral insulae. Neural responses to alcohol cues in these brain regions correlated positively with subjective craving for alcohol and positive expectations of alcohol׳s effects. Moreover, alcohol cue-reactivity in the left dorsal striatum predicted time to first severe relapse. Current results show that alcohol-dependent G-allele carriers׳ increased cue-reactivity is associated with an increased relapse risk. This suggests that genotype effects on cue-reactivity might link the OPRM1 A118G risk allele with an increased relapse risk that was reported in earlier studies. From a clinical perspective, risk-allele carriers might benefit from treatments, such as neuro-feedback or extinction-based therapy that are suggested to reduce mesolimbic reactivity.
内源性阿片系统参与酒精使用障碍的病理生理学。阿片系统的遗传变异改变了对酒精的神经和行为反应。特别是，μ-阿片受体基因（OPRM1）中的单核苷酸多态性 rs1799971（A118G）被认为调节与酒精相关的表型和中脑边缘多巴胺能系统的神经反应。关于这些变化的临床意义知之甚少。本研究在一组戒酒的酒精依赖患者中，研究了基因型对酒精线索和复饮的主观和神经反应的影响。功能性磁共振成像（fMRI）用于研究 81 名戒酒的酒精依赖患者的酒精线索反应和饮酒结果。G 等位基因携带者在左侧背侧纹状体和双侧岛叶显示出增强的 fMRI 线索反应。这些脑区的酒精线索反应与对酒精的主观渴求以及对酒精效果的积极期望呈正相关。此外，左侧背侧纹状体的酒精线索反应预测了首次严重复发的时间。目前的结果表明，酒精依赖的 G 等位基因携带者增加的线索反应与更高的复发风险相关。这表明，阿片受体基因 OPRM1 A118G 风险等位基因对线索反应的影响可能与早期研究报告的更高的复发风险有关。从临床角度来看，携带风险等位基因的患者可能受益于治疗，例如神经反馈或基于消退的治疗，这些治疗被认为可以降低中脑边缘反应性。
