Importance General and specific factors of psychopathology are associated with future adverse outcomes, indicating that they might be useful for identifying individuals at greatest risk. However, it remains unknown if these associations are attributable to confounders that may influence both the psychopathology factors and later outcomes. Objective To analyze associations between psychopathology factors and clinically relevant outcomes within family pairs, adjusting for unmeasured confounds by applying co-twin control and sibling comparison designs. Design, Setting, and Participants This longitudinal cohort study with a follow-up range of 9 to 13 years included all Swedish twins born from 1959 to 1985 who participated in the Study of Twin Adults: Genes and Environment (60% response rate) and the oldest pair of all Swedish siblings born from 1959 to 1985 per the Multi-Generation Register. Twins were evaluated based on responses to a hierarchical factor model derived using multivariate statistics. Sibling pairs were evaluated based on psychiatric diagnoses per the Swedish National Patient Register. Information on outcome events and prescriptions were derived from the National Patient Register, Prescribed Drug Register, and Crime Register. Baseline assessment was in August 2005, and data were analyzed from January 2022 to February 2023. Exposures Hierarchical factor model consisting of 1 general and 4 specific factors fit to 48 psychiatric symptoms on which twin participants self-reported in 2005 and 1 general and 3 specific factors fit to 9 register-based psychiatric diagnoses assigned to sibling participants prior to 2005. Main Outcomes and Measures Outcomes consisted of 7 register-based events occurring after 2005, including suicidal behavior, substance overdoses, and criminal suspicion or convictions (data available until the end of 2013), and prescription of antidepressants, antialcohol or antiopioid medication, antipsychotics, and stimulants (data available until the end of 2017). Results The study included 32 328 twins (mean [SD] age, 34 [8] years; 16 076 [49.73%] male) and 1 942 106 siblings (mean [SD] age, 34 [7] years; 991 500 [51.05%] male). General psychopathology was significantly associated with all 7 outcomes within sibling pairs (mean within-pair odds ratio [OR], 2.28; 95% CI, 2.19-2.37) and dizygotic twin pairs (within-pairs OR, 1.65; 95% CI, 1.38-1.98) and with 3 outcomes within monozygotic twin pairs (mean within-pairs OR, 1.77; 95% CI, 1.35-2.36). Within sibling pairs, the specific internalizing factor was associated with antidepressant prescriptions (within-pairs OR, 1.65; 95% CI, 1.59-1.71), the specific substance misuse factor was associated prescription of antialcohol and antiopioid medication (within-pairs OR, 2.36; 95% CI, 2.20-2.54), and the specific psychotic factor was associated with antipsychotic medications (within-pairs OR, 1.61; 95% CI, 1.51-1.72). Similar results emerged within twin pairs. Conclusion and Relevance In this cohort study, general psychopathology was significantly associated with all 7 outcomes within sibling and dizygotic twin pairs and 3 outcomes within monozygotic twin pairs at 10 years. Within twin and sibling pairs, the specific factors were primarily associated with related outcomes. Several of the associations in this cohort study could not be attributed to unmeasured confounds shared by family members, suggesting that interventions toward broad psychopathology dimensions might help reduce the risk of future clinically relevant events.

中文翻译：

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瑞典成年双胞胎和兄弟姐妹的一般和特定精神病理学因素与 10 年临床相关结果之间的关联。

重要性 精神病理学的一般和特定因素与未来的不良后果相关，表明它们可能有助于识别风险最大的个体。然而，目前尚不清楚这些关联是否可归因于可能影响精神病理学因素和后续结果的混杂因素。目的 分析家庭配对中精神病理学因素与临床相关结果之间的关联，通过应用双胞胎对照和兄弟姐妹比较设计来调整未测量的混杂因素。设计、背景和参与者 这项追踪范围为 9 至 13 年的纵向队列研究包括 1959 年至 1985 年出生的所有瑞典双胞胎，他们参与了双胞胎成人研究：基因与环境（回复率为 60%），以及根据多代登记册，出生于 1959 年至 1985 年的瑞典最年长的兄弟姐妹。根据对使用多元统计得出的分层因素模型的反应来评估双胞胎。根据瑞典国家患者登记册的精神病学诊断对兄弟姐妹进行评估。有关结果事件和处方的信息来自国家患者登记册、处方药物登记册和犯罪登记册。基线评估于2005年8月进行，数据分析时间为2022年1月至2023年2月。暴露 分层因素模型由 1 个一般因素和 4 个具体因素组成，适合双胞胎参与者在 2005 年自我报告的 48 种精神症状，以及 1 个一般因素和 3 个具体因素，适合 2005 年之前分配给兄弟姐妹参与者的 9 种基于登记的精神病诊断。结果和措施 结果包括 2005 年之后发生的 7 起基于登记的事件，包括自杀行为、药物过量、刑事嫌疑或定罪（数据截至 2013 年底），以及抗抑郁药、抗酒精或抗阿片类药物、抗精神病药和抗抑郁药的处方。兴奋剂（数据截至 2017 年底）。结果 该研究包括 32 328 名双胞胎（平均 [SD] 年龄，34 [8] 岁；16 076 [49.73%] 男性）和 1 942 106 名兄弟姐妹（平均 [SD] 年龄，34 [7] 岁；991 500 [51.05] ％] 男性）。一般精神病理学与兄弟姐妹内的所有 7 个结果显着相关（平均对内比值比 [OR]，2.28；95% CI，2.19-2.37）和异卵双胞胎（对内 OR，1.65；95% CI，1.38） -1.98），同卵双胞胎中有 3 个结果（平均配对内 OR，1.77；95% CI，1.35-2.36）。在兄弟姐妹中，特定的内化因素与抗抑郁药物处方相关（配对内 OR，1.65；95% CI，1.59-1.71），特定的物质滥用因素与抗酒精和抗阿片类药物处方相关（配对内 OR，2.36） ；95% CI，2.20-2.54），并且特定的精神病因素与抗精神病药物相关（组内 OR，1.61；95% CI，1.51-1.72）。双胞胎中也出现了类似的结果。结论和相关性 在这项队列研究中，一般精神病理学与 10 岁时兄弟姐妹和异卵双胞胎中的所有 7 个结果以及同卵双胞胎中的 3 个结果显着相关。在双胞胎和兄弟姐妹中，特定因素主要与相关结果相关。这项队列研究中的一些关联不能归因于家庭成员共享的未测量的混杂因素，这表明对广泛的精神病理学维度的干预可能有助于降低未来临床相关事件的风险。