Importance Alcohol misuse in adolescence is a leading cause of disability and mortality in youth and is associated with higher risk for alcohol use disorder. Brain mechanisms underlying risk of alcohol misuse may inform prevention and intervention efforts. Objective To identify neuromarkers of alcohol misuse using a data-driven approach, with specific consideration of neurodevelopmental sex differences. Design, Setting, and Participants Longitudinal multisite functional magnetic resonance imaging (fMRI) data collected at ages 14 and 19 years were used to assess whole-brain patterns of functional organization associated with current and future alcohol use risk as measured by the Alcohol Use Disorder Identification Test (AUDIT). Primary data were collected by the IMAGEN consortium, a European multisite study of adolescent neurodevelopment. Model generalizability was further tested using data acquired in a single-site study of college alcohol consumption conducted in the US. The primary sample was a developmental cohort of 1359 adolescents with neuroimaging, phenotyping, and alcohol use data. Model generalizability was further assessed in a separate cohort of 114 individuals. Main Outcomes and Measures Brain-behavior model accuracy, as defined by the correspondence between model-predicted and actual AUDIT scores in held-out testing data, Bonferroni corrected across the number of models run at each time point, 2-tailed α < .008, as determined via permutation testing. Results Among 1359 individuals in the study, the mean (SD) age was 14.42 (0.40) years, and 729 individuals (54%) were female. The data-driven, whole-brain connectivity approach identified networks associated with vulnerability for future and current AUDIT-defined alcohol use risk (primary outcome, as specified above, future: ρ, 0.22; P < .001 and present: ρ, 0.27; P < .001). Results further indicated sex divergence in the accuracies of brain-behavior models, such that female-only models consistently outperformed male-only models. Specifically, female-only models identified networks conferring vulnerability for future and current severity using data acquired during both reward and inhibitory fMRI tasks. In contrast, male-only models were successful in accurately identifying networks using data acquired during the inhibitory control-but not reward-task, indicating domain specificity of alcohol use risk networks in male adolescents only. Conclusions and Relevance These data suggest that interventions focusing on inhibitory control processes may be effective in combating alcohol use risk in male adolescents but that both inhibitory and reward-related processes are likely of relevance to alcohol use behaviors in female adolescents. They further identify novel networks of alcohol use risk in youth, which may be used to identify adolescents who are at risk and inform intervention efforts.

中文翻译：

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大脑网络和青少年饮酒。

重要性 青春期酗酒是青少年残疾和死亡的主要原因，并且与酒精使用障碍的较高风险相关。酗酒风险背后的大脑机制可能会为预防和干预工作提供信息。目的 使用数据驱动的方法识别酒精滥用的神经标志物，并特别考虑神经发育的性别差异。设计、设置和参与者 使用 14 岁和 19 岁时收集的纵向多部位功能磁共振成像 (fMRI) 数据来评估与当前和未来饮酒风险相关的全脑功能组织模式（通过酒精使用障碍识别来测量）测试（审核）。主要数据由 IMAGEN 联盟收集，这是一项针对青少年神经发育的欧洲多中心研究。使用在美国进行的大学饮酒单点研究中获得的数据进一步测试了模型的普遍性。主要样本是 1359 名青少年的发育队列，拥有神经影像学、表型分析和饮酒数据。在 114 名个体组成的单独队列中进一步评估了模型的普遍性。主要结果和测量 大脑行为模型准确性，由保留测试数据中模型预测分数与实际 AUDIT 分数之间的对应关系定义，Bonferroni 在每个时间点运行的模型数量上进行校正，2 尾 α < .008 ，通过排列测试确定。结果 在研究中的 1359 名个体中，平均 (SD) 年龄为 14.42 (0.40) 岁，其中 729 名个体 (54%) 为女性。数据驱动的全脑连接方法确定了与未来和当前审计定义的饮酒风险脆弱性相关的网络（主要结果，如上所述，未来：ρ，0.22；P < .001，现在：ρ，0.27； P < .001)。结果进一步表明，大脑行为模型的准确性存在性别差异，仅女性模型的表现始终优于仅男性模型。具体来说，仅限女性的模型使用奖励和抑制性功能磁共振成像任务期间获取的数据来识别网络在未来和当前严重性方面的脆弱性。相比之下，仅限男性的模型成功地使用抑制控制（但不是奖励任务）期间获得的数据准确识别网络，表明仅男性青少年饮酒风险网络的领域特异性。结论和相关性这些数据表明，侧重于抑制控制过程的干预措施可能有效地对抗男性青少年的饮酒风险，但抑制和奖励相关过程可能与女性青少年的饮酒行为相关。他们进一步确定了青少年饮酒风险的新网络，这可用于识别处于危险中的青少年并为干预工作提供信息。