Zabik Nicole L, Flook Elizabeth A, Feola Brandee, Benningfield Margaret M, Silveri Marisa M, Winder Danny G, Blackford Jennifer Urbano
Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha, Nebraska, USA.
Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Alcohol Clin Exp Res (Hoboken). 2024 Sep;48(9):1716-1727. doi: 10.1111/acer.15407. Epub 2024 Aug 24.
Anxiety during early alcohol abstinence, likely resulting from neural changes caused by chronic alcohol use, contributes to high relapse rates. Studies in rodents show heightened activation during early abstinence in the bed nucleus of the stria terminalis (BNST)-a neural hub for anxiety-and its extended anxiety-related corticolimbic network. Despite the clinical importance of early abstinence, few studies investigate the underlying neural mechanisms.
To address this gap, we investigated brain function in early alcohol abstinence (EA = 20, 9 women) relative to controls (HC = 20, 11 women) using an unpredictable threat task shown to engage the BNST and corticolimbic brain regions involved in anxiety and alcohol use disorder (AUD). Group, anxiety, and sex were predictors used to determine whole-brain activation and BNST functional connectivity.
We found widespread interactions of group × anxiety and group × anxiety × sex for both activation and BNST connectivity during unpredictable threat. In the EA group, higher anxiety was correlated with activation in the BNST, rostral anterior cingulate cortex (ACC), insula (men only), and dorsal ACC (men only). In the HC group, higher anxiety was negatively correlated with activation in the BNST, nucleus accumbens, thalamus, and insula (men only). For connectivity, anxiety was positively correlated in EA and negatively correlated in HC, between the BNST and the amygdala, ventromedial prefrontal cortex (PFC), and dorsomedial PFC; EA men showed stronger BNST-vmPFC connectivity than HC men.
These novel findings provide preliminary evidence for alterations in the BNST and anxiety-related corticolimbic brain regions in early alcohol abstinence, adding to growing literature in humans supporting the BNST's role in anxiety and sex-dependent effects of chronic alcohol use.
早期戒酒期间的焦虑，可能源于长期饮酒引起的神经变化，这是导致高复发率的原因之一。对啮齿动物的研究表明，在早期戒酒期间，终纹床核（BNST，一个与焦虑相关的神经中枢）及其扩展的与焦虑相关的皮质边缘网络的激活增强。尽管早期戒酒在临床上具有重要意义，但很少有研究探讨其潜在的神经机制。
为了填补这一空白，我们使用一项不可预测的威胁任务，研究了早期戒酒者（EA = 20例，9名女性）相对于对照组（HC = 20例，11名女性）的脑功能，该任务已被证明能激活参与焦虑和酒精使用障碍（AUD）的BNST和皮质边缘脑区。将组、焦虑和性别作为预测因素，用于确定全脑激活和BNST功能连接性。
我们发现，在不可预测的威胁期间，组×焦虑和组×焦虑×性别在激活和BNST连接性方面存在广泛的相互作用。在EA组中，较高的焦虑与BNST、喙前扣带回皮质（ACC）、岛叶（仅男性）和背侧ACC（仅男性）的激活相关。在HC组中，较高的焦虑与BNST、伏隔核、丘脑和岛叶（仅男性）的激活呈负相关。对于连接性，焦虑在EA组中与BNST和杏仁核、腹内侧前额叶皮质（PFC）以及背内侧PFC之间呈正相关，在HC组中呈负相关；EA组男性的BNST- vmPFC连接性比HC组男性更强。
这些新发现为早期戒酒期间BNST和与焦虑相关的皮质边缘脑区的改变提供了初步证据，进一步丰富了支持BNST在焦虑和长期饮酒的性别依赖性影响中作用的人体研究文献。
