Department of Psychology and Neuroscience, University of North Carolina, Chapel Hill, North Carolina, USA.
Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, North Carolina, USA.
Hum Brain Mapp. 2023 Apr 15;44(6):2436-2450. doi: 10.1002/hbm.26221. Epub 2023 Feb 1.
Childhood maltreatment (CM) and a family history (FH) of alcohol use disorder (AUD) are each associated with increased impulsivity. However, their unique or shared brain targets remain unknown. Furthermore, both CM and FH demonstrate sex-dependent effects on brain and behavior. We hypothesized that CM and FH interact in brain regions involved in impulsivity with sex-dependent effects. 144 first-year college students (18-19 years old) with varying experiences of CM and/or FH but without current AUD performed an fMRI stop-signal task. We tested interactions between FH, CM, and sex on task performance and blood oxygen level-dependent (BOLD) signal during successful inhibitions. We examined correlations between BOLD response and psychiatric symptoms. Significant three-way interactions of FH, CM, and sex were detected for brain and behavioral data, largely driven by male subjects. In males, CM was associated with poorer response inhibition but only for those with less FH; males with higher levels of both CM and FH demonstrated better response inhibition. Three-way interaction effects on voxel-wise BOLD response during response inhibition were found in bilateral middle frontal gyrus, left inferior frontal gyrus, dorsomedial prefrontal cortex, and posterior cingulate cortex. Network-level analyses implicated the left frontoparietal network, executive control network, and default-mode network. Greater BOLD response in these networks correlated with lower depressive, impulsive, and attentional symptoms, reduced alcohol misuse, greater resilience scores, and heightened trait anxiety. The results highlight sex-divergent effects of heritable and environmental risk factors that may account for sex-dependent expression of psychopathology in response to risk factors.
儿童虐待（CM）和酒精使用障碍（AUD）家族史（FH）均与冲动性增加有关。然而，它们的独特或共同的大脑靶点尚不清楚。此外，CM 和 FH 均表现出对大脑和行为的性别依赖性影响。我们假设 CM 和 FH 在与冲动性相关的大脑区域相互作用，并具有性别依赖性的影响。144 名一年级大学生（18-19 岁）具有不同的 CM 和/或 FH 经历，但没有当前的 AUD，进行了 fMRI 停止信号任务。我们测试了 FH、CM 和性别对任务表现和成功抑制期间血氧水平依赖（BOLD）信号的相互作用。我们检查了 BOLD 反应与精神症状之间的相关性。在大脑和行为数据中检测到 FH、CM 和性别之间的显著三向相互作用，主要由男性驱动。在男性中，CM 与较差的反应抑制有关，但仅针对 FH 较低的男性；CM 和 FH 水平较高的男性表现出更好的反应抑制。在反应抑制期间的 BOLD 反应的三向相互作用效应在双侧额中回、左侧额下回、背内侧前额叶皮层和后扣带回中发现。基于体素的分析表明了左侧额顶网络、执行控制网络和默认模式网络的作用。这些网络中更大的 BOLD 反应与更低的抑郁、冲动和注意力症状、减少的酒精滥用、更高的适应力评分以及更高的特质焦虑相关。研究结果突出了遗传和环境风险因素的性别差异效应，这些因素可能解释了对风险因素的精神病理学的性别依赖性表达。
