Wiers C E, Shumay E, Volkow N D, Frieling H, Kotsiari A, Lindenmeyer J, Walter H, Bermpohl F
National Institute on Alcohol Abuse and Alcoholism, Laboratory of Neuroimaging, National Institutes of Health, Bethesda, MD, USA.
National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, USA.
Transl Psychiatry. 2015 Sep 29;5(9):e648. doi: 10.1038/tp.2015.141.
In alcohol-dependent (AD) patients, alcohol cues induce strong activations in brain areas associated with alcohol craving and relapse, such as the nucleus accumbens (NAc) and amygdala. However, little is known about the influence of depressive symptoms, which are common in AD patients, on the brain's reactivity to alcohol cues. The methylation state of the dopamine transporter gene (DAT) has been associated with alcohol dependence, craving and depression, but its influence on neural alcohol cue reactivity has not been tested. Here, we compared brain reactivity to alcohol cues in 38 AD patients and 17 healthy controls (HCs) using functional magnetic resonance imaging and assessed the influence of depressive symptoms and peripheral DAT methylation in these responses. We show that alcoholics with low Beck's Depression Inventory scores (n=29) had higher cue-induced reactivity in NAc and amygdala than those with mild/moderate depression scores (n=9), though subjective perception of craving was higher in those with mild/moderate depression scores. We corroborated a higher DAT methylation in AD patients than HCs, and showed higher DAT methylation in AD patients with mild/moderate than low depression scores. Within the AD cohort, higher methylation predicted craving and, at trend level (P=0.095), relapse 1 year after abstinence. Finally, we show that amygdala cue reactivity correlated with craving and DAT methylation only in AD patients with low depression scores. These findings suggest that depressive symptoms and DAT methylation are associated with alcohol craving and associated brain processes in alcohol dependence, which may have important consequences for treatment. Moreover, peripheral DAT methylation may be a clinically relevant biomarker in AD patients.
在酒精依赖（AD）患者中，酒精线索会诱发与酒精渴望及复发相关的脑区强烈激活，如伏隔核（NAc）和杏仁核。然而，对于AD患者中常见的抑郁症状对大脑对酒精线索反应性的影响却知之甚少。多巴胺转运体基因（DAT）的甲基化状态与酒精依赖、渴望及抑郁有关，但其对神经酒精线索反应性的影响尚未得到验证。在此，我们使用功能磁共振成像比较了38例AD患者和17名健康对照者（HCs）对酒精线索的脑反应性，并评估了抑郁症状和外周DAT甲基化对这些反应的影响。我们发现，贝克抑郁量表得分低的酗酒者（n = 29）在NAc和杏仁核中线索诱发的反应性高于轻度/中度抑郁得分者（n = 9），尽管轻度/中度抑郁得分者对渴望的主观感受更高。我们证实AD患者的DAT甲基化水平高于HCs，且轻度/中度抑郁得分的AD患者的DAT甲基化水平高于得分低者。在AD队列中，较高的甲基化预示着渴望，且在趋势水平（P = 0.095）上预示着戒酒1年后的复发。最后，我们表明，仅在抑郁得分低的AD患者中，杏仁核线索反应性与渴望及DAT甲基化相关。这些发现表明，抑郁症状和DAT甲基化与酒精依赖中的酒精渴望及相关脑过程有关，这可能对治疗有重要影响。此外，外周DAT甲基化可能是AD患者临床上相关的生物标志物。
