Objective:

Stress and alcohol cue reactivity are associated with poor treatment outcomes in alcohol use disorder (AUD), but sex-specific neural correlates of stress and alcohol cue–induced craving compared with neutral cue–induced craving and of heavy drinking outcomes in AUD have not been examined. Thus, this study prospectively examined these associations and assessed sex differences.

Methods:

Treatment-seeking adults with AUD (N=77; 46 men and 31 women) completed a functional MRI task involving stress, alcohol, and neutral cue exposure with repeated assessments of alcohol craving. Most of these participants (N=72; 43 men and 29 women) then participated in an 8-week standardized behavioral AUD treatment program, during which the percentage of heavy drinking days was assessed.

Results:

Significant increases in both stress and alcohol cue–induced craving relative to neutral cue–induced craving were observed, with a greater alcohol-neutral contrast in craving relative to the stress-neutral contrast among men and equivalent stress-neutral and alcohol-neutral contrasts in craving among women. Whole-brain voxel-based regression analyses showed craving-associated hyperactivation in the neutral condition, but hypoactive prefrontal (ventromedial and lateral prefrontal, supplementary motor, and anterior cingulate regions) and striatal responses during exposure to stressful images (stress-neutral contrast) and alcohol cues (alcohol-neutral contrast), with significant sex differences. Additionally, a higher percentage of heavy drinking days was associated with hypoactivation of the subgenual anterior cingulate cortex and the bed nucleus of the stria terminalis in the stress-neutral contrast among women, hyperactivation of the hypothalamus in the stress-neutral contrast among men, and hyperactivation of the hippocampus in the alcohol-neutral contrast among men.

Conclusions:

Sex differences in stress- and alcohol cue-induced responses in the cortico-striatal-limbic network related to subjective alcohol craving and to heavy drinking indicated that distinct brain circuits underlie alcohol use outcomes in women and men. These findings underscore the need for sex-specific therapeutics to address this neural dysfunction effectively.

中文翻译：

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压力和酒精暗示引起的酒精渴望以及未来酗酒的神经相关性：性别差异的证据

客观的：

压力和酒精提示反应性与酒精使用障碍 (AUD) 的不良治疗结果相关，但与中性提示诱发的渴望相比，压力和酒精提示诱发的渴望的性别特异性神经相关性以及 AUD 中的大量饮酒结果尚未被研究。检查了。因此，本研究前瞻性地研究了这些关联并评估了性别差异。

方法：

患有 AUD 的寻求治疗的成年人（N=77；46 名男性和 31 名女性）完成了一项功能性 MRI 任务，涉及压力、酒精和中性线索暴露，并重复评估酒精渴望。大多数参与者（N=72；43 名男性和 29 名女性）随后参加了为期 8 周的标准化行为 AUD 治疗计划，在此期间评估了酗酒天数的百分比。

结果：

相对于中性提示诱发的渴望，观察到压力和酒精提示诱发的渴望显着增加，相对于压力中性的对比，男性的渴望中酒精中性的对比更大，而男性中压力中性和酒精中性的对比则相同。女人之间的渴望。基于全脑体素的回归分析显示，在中性条件下，渴望相关的过度活跃，但在暴露于压力图像（压力中性对比）和酒精线索（酒精中性对比），具有显着的性别差异。此外，酗酒日的比例较高与女性压力中性对比中膝下前扣带皮层和终纹床核的低活性有关，男性压力中性对比中下丘脑的过度激活，以及男性中酒精中性对比中海马体的过度激活。

结论：

与主观酒精渴望和酗酒相关的皮质-纹状体-边缘网络中压力和酒精提示引起的反应的性别差异表明，不同的大脑回路是女性和男性饮酒结果的基础。这些发现强调需要针对性别的疗法来有效解决这种神经功能障碍。