A family history of alcoholism (FH) increases risk for alcohol use disorder (AUD), yet many at-risk individuals never develop alcohol use problems. FH is associated with intermediate levels of risk phenotypes, whereas distinct, compensatory brain changes likely promote resilience. Although several cognitive, behavioral, and personality factors have been associated with AUD, the relative contributions of these processes and their neural underpinnings to risk or resilience processes remains less clear. We examined whole-brain resting-state functional connectivity (FC) and behavioral metrics from 841 young adults from the Human Connectome Project, including healthy controls, individuals with AUD, and their unaffected siblings. First, we identified functional connections in which unaffected siblings were intermediate between controls and AUD, indicating AUD risk, and those in which siblings diverged, indicating resilience. Canonical correlations relating brain risk and resilience FC to behavioral patterns revealed AUD risk and resilience phenotypes. Risk phenotypes primarily implicated frontal-parietal networks corresponding with executive function, impulsivity, externalizing behaviors, and social-emotional intelligence. Conversely, resilience-related phenotypes were underpinned by networks of medial prefrontal, striatal, temporal, brainstem and cerebellar connectivity, which associated with high trait attention and low antisocial behavior. Additionally, we calculated “polyphenotypic” risk and resilience scores, to investigate how the relative load of risk and resilience phenotypes influenced the probability of an AUD diagnosis. Polyphenotypic scores predicted AUD in a dose-dependent manner. Moreover, resilience phenotypes interacted with risk phenotypes, reducing their effects. The hypothesis-generating results revealed interpretable AUD-related phenotypes and offer brain-informed targets for developing more effective interventions

酗酒 (FH) 家族史会增加酒精使用障碍 (AUD) 的风险，但许多处于危险中的人从未出现酒精使用问题。FH 与中等水平的风险表型相关，而明显的补偿性大脑变化可能会促进恢复力。尽管一些认知、行为和人格因素与 AUD 相关，但这些过程及其神经基础对风险或恢复过程的相对贡献仍不太清楚。我们检查了来自 Human Connectome Project 的 841 名年轻人的全脑静息状态功能连接 (FC) 和行为指标，包括健康对照、AUD 患者及其未受影响的兄弟姐妹。首先，我们确定了未受影响的兄弟姐妹在控制和 AUD 之间的功能联系，表示澳元风险，以及兄弟姐妹分歧的那些，表明弹性。将大脑风险和恢复力 FC 与行为模式相关联的典型相关性揭示了 AUD 风险和恢复力表型。风险表型主要涉及与执行功能、冲动、外化行为和社会情商相对应的额叶-顶叶网络。相反，与弹性相关的表型由内侧前额叶、纹状体、颞叶、脑干和小脑连接网络支撑，这与高特质注意力和低反社会行为相关。此外，我们计算了“多表型”风险和弹性分数，以研究风险和弹性表型的相对负荷如何影响 AUD 诊断的概率。多表型评分以剂量依赖性方式预测 AUD。此外，弹性表型与风险表型相互作用，降低了它们的影响。假设产生的结果揭示了可解释的 AUD 相关表型，并为开发更有效的干预措施提供了大脑知情的目标