Department of Psychiatry, State University of New York, Downstate Medical Center, Brooklyn, NY, USA.
Department of Psychiatry, Washington University School of Medicine in St Louis, St Louis, MO, USA.
Transl Psychiatry. 2021 Mar 15;11(1):166. doi: 10.1038/s41398-021-01281-2.
Predictive models for recovering from alcohol use disorder (AUD) and identifying related predisposition biomarkers can have a tremendous impact on addiction treatment outcomes and cost reduction. Our sample (N = 1376) included individuals of European (EA) and African (AA) ancestry from the Collaborative Study on the Genetics of Alcoholism (COGA) who were initially assessed as having AUD (DSM-5) and reassessed years later as either having AUD or in remission. To predict this difference in AUD recovery status, we analyzed the initial data using multimodal, multi-features machine learning applications including EEG source-level functional brain connectivity, Polygenic Risk Scores (PRS), medications, and demographic information. Sex and ancestry age-matched stratified analyses were performed with supervised linear Support Vector Machine application and were calculated twice, once when the ancestry was defined by self-report and once defined by genetic data. Multifeatured prediction models achieved higher accuracy scores than models based on a single domain and higher scores in male models when the ancestry was based on genetic data. The AA male group model with PRS, EEG functional connectivity, marital and employment status features achieved the highest accuracy of 86.04%. Several discriminative features were identified, including collections of PRS related to neuroticism, depression, aggression, years of education, and alcohol consumption phenotypes. Other discriminated features included being married, employed, medication, lower default mode network and fusiform connectivity, and higher insula connectivity. Results highlight the importance of increasing genetic homogeneity of analyzed groups, identifying sex, and ancestry-specific features to increase prediction scores revealing biomarkers related to AUD remission.
预测从酒精使用障碍 (AUD) 中恢复的模型,并确定相关的易感性生物标志物,可能对成瘾治疗结果和降低成本产生巨大影响。我们的样本(N=1376)包括来自酒精遗传学合作研究 (COGA) 的欧洲 (EA) 和非洲 (AA) 血统的个体,他们最初被评估为患有 AUD(DSM-5),并在几年后重新评估为患有 AUD 或缓解。为了预测 AUD 恢复状态的这种差异,我们使用多模态、多特征机器学习应用程序分析了初始数据,包括 EEG 源水平功能脑连接、多基因风险评分 (PRS)、药物和人口统计学信息。进行了性别和祖先年龄匹配的分层分析,使用有监督的线性支持向量机应用程序进行分析,并进行了两次计算,一次是根据自我报告定义祖先,一次是根据遗传数据定义祖先。多特征预测模型比基于单一领域的模型具有更高的准确性得分,并且当基于遗传数据定义祖先时,男性模型的得分更高。具有 PRS、EEG 功能连接、婚姻和就业状况特征的 AA 男性组模型达到了 86.04%的最高准确性。确定了几个有区别的特征,包括与神经质、抑郁、攻击性、受教育年限和酒精消费表型相关的 PRS 集合。其他有区别的特征包括已婚、就业、药物治疗、默认模式网络和梭状回连接降低,以及脑岛连接增加。结果强调了增加分析群体遗传同质性、确定性别和祖先特异性特征以提高预测分数的重要性,这些特征揭示了与 AUD 缓解相关的生物标志物。