Addiction Sciences Division, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston.
JAMA Psychiatry. 2023 Nov 1;80(11):1150-1159. doi: 10.1001/jamapsychiatry.2023.2726.
Reward circuitry dysfunction is a candidate mechanism of co-occurring bipolar disorder and alcohol use disorder (BD + AUD) that remains understudied. This functional magnetic resonance imaging (fMRI) research represents the first evaluation of alcohol cue reward processing in BD + AUD.
To determine how alcohol cue processing in individuals with BD + AUD may be distinct from that of individuals with AUD or BD alone.
DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional case-control study (April 2013-June 2018) followed a 2 × 2 factorial design and included individuals with BD + AUD, AUD alone, BD alone, and healthy controls. A well-validated visual alcohol cue reactivity fMRI paradigm was administered to eligible participants following their demonstration of 1 week or more of abstinence from alcohol and drugs assessed via serial biomarker testing. Study procedures were completed at the Medical University of South Carolina. Analysis took place between June and August 2022.
Past-week mood symptoms were rated by clinicians using the Montgomery-Åsberg Depression Rating Scale and Young Mania Rating Scale. The Alcohol Dependence Scale, Obsessive-Compulsive Drinking Scale, and Barratt Impulsiveness Scale were included questionnaires. Functional MRI whole-brain data were analyzed along with percent signal change within a priori regions of interest located in the ventral striatum, dorsal striatum, and ventromedial prefrontal cortex. Exploratory analyses of associations between cue reactivity and select behavioral correlates (alcohol craving, impulsivity, maximum number of alcohol drinks on a single occasion, and days since last alcohol drink) were also performed.
Of 112 participants, 28 (25.0%) had BD + AUD, 26 (23.2%) had AUD alone, 31 (27.7%) had BD alone, and 27 (24.1%) were healthy controls. The mean (SD) age was 38.7 (11.6) years, 50 (45.5%) were female, 33 (30%) were smokers, and 37 (34.9%) reported recent alcohol consumption. Whole-brain analyses revealed a BD × AUD interaction (F = 10.64; P = .001; η2 = 0.09) within a cluster spanning portions of the right inferior frontal gyrus and insula. Region of interest analyses revealed a main association of BD (F = 8.02; P = .006; η2 = 0.07) within the dorsal striatum. In each instance, individuals with BD + AUD exhibited reduced activation compared with all other groups who did not significantly differ from one another. These hypoactivations were associated with increased impulsivity and obsessive-compulsive alcohol craving exclusively among individuals with BD + AUD.
The findings of this study suggest conceptualizing reward dysfunction in BD + AUD by the potential interaction between blunted reward responsivity and deficient inhibitory control may help guide treatment development strategies. To this end, reduced right inferior frontal gyrus and insula alcohol cue reactivity represents a novel candidate biomarker of BD + AUD that may respond to pharmacological interventions targeting impulsivity-related neural mechanisms for improved executive control.
奖赏回路功能障碍是双相障碍和酒精使用障碍（BD+AUD）共病的候选机制，但研究仍不够充分。这项功能磁共振成像（fMRI）研究代表了对 BD+AUD 个体中酒精线索奖赏加工的首次评估。
确定 BD+AUD 个体的酒精线索处理方式与 AUD 或 BD 个体有何不同。
设计、设置和参与者：这项病例对照研究（2013 年 4 月至 2018 年 6 月）采用 2×2 析因设计，包括 BD+AUD、AUD 单独、BD 单独和健康对照组的个体。合格的参与者在经过 1 周或更长时间的酒精和药物戒断后，通过连续生物标志物测试进行评估，随后接受了经过充分验证的视觉酒精线索反应性 fMRI 范式。研究程序在南卡罗来纳医科大学完成。分析于 2022 年 6 月至 8 月进行。
临床医生使用蒙哥马利-Åsberg 抑郁评定量表和 Young 躁狂评定量表对参与者过去一周的情绪症状进行了评分。还包括酒精依赖量表、强迫性饮酒量表和巴瑞特冲动量表在内的问卷。对全脑功能磁共振成像数据以及位于腹侧纹状体、背侧纹状体和腹内侧前额叶皮层的预先设定的感兴趣区的信号百分比变化进行了分析。还进行了酒精线索反应与选定行为相关性（酒精渴求、冲动、单次饮酒的最大数量和上次饮酒的天数）之间的关联的探索性分析。
在 112 名参与者中，28 名（25.0%）患有 BD+AUD，26 名（23.2%）患有 AUD 单独，31 名（27.7%）患有 BD 单独，27 名（24.1%）为健康对照组。参与者的平均（SD）年龄为 38.7（11.6）岁，50 名（45.5%）为女性，33 名（30%）为吸烟者，37 名（34.9%）报告最近饮酒。全脑分析显示，BD 和 AUD 之间存在交互作用（F=10.64；P=.001；η2=0.09），该作用跨越了右侧额下回和脑岛的部分区域。感兴趣区分析显示，BD 存在主要关联（F=8.02；P=.006；η2=0.07），位于背侧纹状体。在每种情况下，BD+AUD 个体的激活均低于其他所有组，而其他组之间无显著差异。这些低激活与 BD+AUD 个体的冲动和强迫性酒精渴求增加有关。
这项研究的结果表明，通过潜在的奖赏反应迟钝和抑制控制不足之间的相互作用来概念化 BD+AUD 中的奖赏功能障碍，可能有助于指导治疗开发策略。为此，右额下回和脑岛酒精线索反应性降低代表了一种新的 BD+AUD 候选生物标志物，可能对针对改善执行控制的冲动相关神经机制的药物干预有反应。
