Pol-Fuster Josep, Fernández de la Cruz Lorena, Beucke Jan C, Hesselmark Eva, Crowley James J, de Schipper Elles, Brikell Isabell, Chang Zheng, D'Onofrio Brian M, Larsson Henrik, Lichtenstein Paul, Kuja-Halkola Ralf, Mataix-Cols David
Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
Biol Psychiatry. 2025 Apr 1;97(7):672-677. doi: 10.1016/j.biopsych.2024.09.004. Epub 2024 Sep 14.
Postinfectious autoimmune processes have been proposed as potential causal risk factors for obsessive-compulsive disorder (OCD). In this large population-based study, we aimed to clarify the familial coaggregation pattern between severe infections and OCD across clusters of relatives with varying degrees of relatedness.
We identified 4,916,898 individuals born in Sweden between 1960 and 2008 and followed them until the end of 2020. Each individual was linked to their first-, second-, and third-degree relatives, including monozygotic and dizygotic twins, mothers, fathers, full siblings, maternal and paternal half siblings, aunts, uncles, and cousins. OCD and infection diagnoses from inpatient and specialized outpatient settings were retrieved from the Swedish National Patient Register. We compared the risk of OCD in relatives of probands with severe infections to those of probands without severe infections. Cox proportional hazard regression models, incorporating time-varying exposures, were used to estimate hazard ratios. Dose-response associations were examined using logistic regression models.
Relatives of probands with severe infections had a higher risk of OCD, which increased with genetic relatedness, with hazard ratios (95% CI) ranging from 1.46 (1.07-1.98) in monozygotic twins to 1.10 (1.09-1.11) in cousins. The results remained robust after adjusting for severe infections among relatives, OCD in probands, and comorbid autoimmune disorders in both probands and relatives. A dose-response association was observed between the number of infections in the probands and their odds of OCD, as well as in their relatives.
The results strongly suggest that the association between severe infections and OCD may be largely driven by shared genetic factors.
感染后自身免疫过程被认为是强迫症（OCD）潜在的因果风险因素。在这项基于大规模人群的研究中，我们旨在阐明严重感染与强迫症在不同程度亲属群体中的家族聚集模式。
我们确定了1960年至2008年在瑞典出生的4916898人，并对他们进行随访直至2020年底。每个人都与他们的一级、二级和三级亲属建立联系，包括同卵和异卵双胞胎、母亲、父亲、亲兄弟姐妹、同父异母或同母异父的兄弟姐妹、姑姑、叔叔和表亲。强迫症和感染诊断信息从瑞典国家患者登记处获取，这些诊断来自住院患者和专科门诊患者。我们比较了患有严重感染的先证者亲属患强迫症的风险与未患有严重感染的先证者亲属的风险。使用纳入时变暴露因素的Cox比例风险回归模型来估计风险比。使用逻辑回归模型检验剂量反应关联。
患有严重感染的先证者亲属患强迫症的风险更高，且随着遗传相关性增加，风险比（95%可信区间）范围从同卵双胞胎中的1.46（1.07 - 1.98）到表亲中的1.10（1.09 - 1.11）。在对亲属中的严重感染、先证者中的强迫症以及先证者和亲属中的合并自身免疫性疾病进行校正后，结果仍然稳健。在先证者及其亲属的感染次数与他们患强迫症的几率之间观察到剂量反应关联。
结果强烈表明，严重感染与强迫症之间的关联可能在很大程度上由共同的遗传因素驱动。
