Importance Cannabis use disorder (CUD) is increasing in the US. Clarification of the potential mechanisms underlying the comorbidity between mood disorders and CUD may help prevent CUD. Objective To examine co-occurrence and familial aggregation of CUD and mood disorder subtypes. Design, Setting, and Participants In this cross-sectional, community-based study in the Washington, DC, metropolitan area, semistructured diagnostic interviews and family history reports assessed lifetime DSM-IV disorders in probands and relatives. Familial aggregation and coaggregation of CUD with mood disorders were estimated via mixed-effects models, adjusting for age, sex, recruitment source, and comorbid mood, anxiety, and other substance use disorders. A total of 586 adult probands (186 with bipolar disorder; 55 with CUD) and 698 first-degree relatives (91 with bipolar disorder; 68 with CUD) were recruited from a community screening of the greater Washington, DC, metropolitan area from May 2004 to August 2020. Inclusion criteria were ability to speak English, and availability and consent to contact at least 2 living first-degree relatives. Main Outcomes and Measures Lifetime CUD in first-degree relatives. Results Of 586 probands, 395 (67.4%) were female; among 698 relatives, 437 (62.6%) were female. The mean (SD) age was 47.5 (15.2) years for probands and 49.6 (18.0) years for relatives. In the proband group, 82 participants (14.0%) self-identified as African American or Black, 467 (79.7%) as White, and 37 (6.3%) as American Indian or Alaska Native, Asian, more than one race, or another race or ethnicity or declined to respond. In the relative group, 53 participants (7.6%) self-identified as African American or Black, 594 (85.1%) as White, and 51 (7.3%) as American Indian or Alaska Native, Asian, more than one race, or another race or ethnicity or declined to respond. These groups were combined to protect privacy owing to small numbers. CUD in probands (55 [9.4%]) was associated with an increase in CUD in relatives (adjusted odds ratio [aOR], 2.64; 95% CI, 1.20-5.79; P = .02). Bipolar disorder II (BP-II) in probands (72 [12.3%]) was also associated with increased risk of CUD in relatives (aOR, 2.57; 95% CI, 1.06-6.23; P = .04). However, bipolar disorder I (114 [19.5%]) and major depressive disorder (192 [32.8%]) in probands were not significantly associated with CUD in relatives. Among relatives, CUD was associated with BP-II (aOR, 4.50; 95% CI, 1.72-11.77; P = .002), major depressive disorder (aOR, 3.64; 95% CI, 1.78-7.45; P < .001), and mean (SD) age (42.7 [12.8] years with CUD vs 50.3 [18.3] years without CUD; aOR, 0.98; 95% CI, 0.96-1.00; P = .02). Familial coaggregation of BP-II with CUD was attenuated by the inclusion of comorbid anxiety disorders. Further, rates of CUD were highest in relatives with both a familial and individual history of BP-II (no familial or individual history of BP-II: 41 [7.2%]; familial history but no individual history of BP-II: 13 [19.1%]; individual history but no familial history of BP-II: 10 [22.2%]; familial and individual history of BP-II: 4 [28.6%]; Fisher exact test, P < .001). The onset of mood disorder subtypes preceded CUD in probands and relatives in most cases. Conclusions and Relevance The findings confirmed a familial aggregation of CUD. The increase in risk of CUD among relatives of probands with BP-II suggests that CUD may share a common underlying diathesis with BP-II. Taken together with the temporal precedence of depression and mania with respect to CUD onset, these findings highlight a potential role for BP-II intervention as CUD prevention.

中文翻译：

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受控家庭研究中重度抑郁症、双相情感障碍和大麻使用障碍的合并症和合并症。

重要性 在美国，大麻使用障碍 (CUD) 正在增加。阐明情绪障碍与 CUD 共病的潜在机制可能有助于预防 CUD。目的 研究 CUD 和心境障碍亚型的共同发生和家族聚集性。设计、设置和参与者 在这项在华盛顿特区大都市区进行的基于社区的横断面研究中，半结构化诊断访谈和家族史报告评估了先证者和亲属的终生 DSM-IV 疾病。通过混合效应模型估计 CUD 与情绪障碍的家族聚集和共聚集，调整年龄、性别、招募来源和共病情绪、焦虑和其他物质使用障碍。共有 586 名成年先证者（186 名患有双相情感障碍；55 名患有 CUD）和 698 名一级亲属（91 名患有躁郁症；68 名患有 CUD）是从 2004 年 5 月至 2020 年 8 月对大华盛顿特区大都市区进行的社区筛查中招募的。纳入标准是能够说英语，可用性并同意联系至少 2 个活着的一级亲属。主要结果和措施 一级亲属的终生 CUD。结果586名先证者中，女性395名（67.4%）；698名亲属中，女性437名（62.6%）。先证者的平均 (SD) 年龄为 47.5 (15.2) 岁，亲属为 49.6 (18.0) 岁。在先证者组中，82 名参与者 (14.0%) 自认为是非裔美国人或黑人，467 名 (79.7%) 是白人，37 名 (6.3%) 是美洲印第安人或阿拉斯加原住民、亚洲人、一个以上种族或另一个种族或民族或拒绝回应。在亲戚群里，53 名参与者 (7.6%) 自认为是非裔美国人或黑人，594 名 (85.1%) 是白人，51 名 (7.3%) 是美洲印第安人或阿拉斯加原住民、亚裔、多于一个种族或其他种族或族裔或被拒绝回复。由于人数较少，这些团体被合并以保护隐私。先证者中的 CUD (55 [9.4%]) 与亲属中的 CUD 增加有关（调整后的比值比 [aOR]，2.64；95% CI，1.20-5.79；P = .02）。先证者中的双相情感障碍 II (BP-II) (72 [12.3%]) 也与亲属中 CUD 风险增加相关 (aOR，2.57；95% CI，1.06-6.23；P = .04)。然而，先证者中的双相情感障碍 I (114 [19.5%]) 和重度抑郁症 (192 [32.8%]) 与亲属中的 CUD 没有显着相关性。在亲属中，CUD 与 BP-II 相关（aOR，4.50；95% CI，1.72-11.77；P = .002），重度抑郁症（aOR，3.64；95% CI，1.78-7.45；P < .001）和平均 (SD) 年龄（42.7 [12.8] 岁，有 CUD vs 50.3 [18.3] 岁，无 CUD；aOR，0.98；95 % 置信区间，0.96-1.00；P = .02）。BP-II 与 CUD 的家族性聚集因合并焦虑症而减弱。此外，具有 BP-II 家族史和个人史的亲属的 CUD 率最高（无 BP-II 家族史或个人史：41 [7.2%]；有家族史但无 BP-II 个人史：13 [ 19.1%]；个人病史但无 BP-II 家族史：10 [22.2%]；BP-II 家族史和个人病史：4 [28.6%]；Fisher 精确检验，P < .001）。在大多数情况下，先证者和亲属的情绪障碍亚型的发作先于 CUD。结论和相关性 研究结果证实了 CUD 的家族聚集。BP-II 先证者亲属中 CUD 风险的增加表明，CUD 可能与 BP-II 具有共同的潜在素质。结合抑郁症和躁狂症在 CUD 发作方面的时间优先顺序，这些发现突出了 BP-II 干预作为 CUD 预防的潜在作用。