Tabrizi Fara, Rosén Jörgen, Grönvall Hampus, William-Olsson Victor Rahimzadeh, Arner Erik, Magnusson Patrik Ke, Palm Camilla, Larsson Henrik, Viktorin Alexander, Bernhardsson Jens, Björkdahl Johanna, Jansson Billy, Sundin Örjan, Zhou Xuan, Speed Doug, Åhs Fredrik
Department of Psychology and Social Work, Mid Sweden University, Ostersund, Sweden.
Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
Transl Psychiatry. 2025 Mar 27;15(1):98. doi: 10.1038/s41398-025-03325-3.
Anxiety and depression commonly occur together resulting in worse health outcomes than when they occur in isolation. We aimed to determine whether the genetic liability for comorbid anxiety and depression was greater than when anxiety or depression occurred alone. Data from 12,792 genotyped twins (ages 38-85) were analysed, including 1,986 complete monozygotic and 1,594 complete dizygotic pairs. Outcomes were prescription of antidepressant and anxiolytic drugs, as defined by the World Health Organization Anatomical Therapeutic Chemical Classification System (ATC) convention, for comorbid anxiety and depression (n = 1028), anxiety only (n = 718), and depression only (n = 484). Heritability of each outcome was estimated using twin modelling, and the influence of common genetic variation was assessed from polygenic scores (PGS) for depressive symptoms, anxiety, and 40 other traits. Heritability of comorbid anxiety and depression was 79% compared with 41% for anxiety and 50% for depression alone. The PGS for depressive symptoms likewise predicted more variation in comorbid anxiety and depression (adjusted odds ratio per SD PGS = 1.53, 95% CI = 1.43-1.63; ΔR = 0.031, ΔAUC = 0.044) than the other outcomes, with nearly identical results when comorbid anxiety and depression was defined by International Classification of Diseases (ICD) diagnoses (adjusted odds ratio per SD PGS = 1.70, 95% CI = 1.53-1.90; ΔR = 0.036, ΔAUC = 0.051). Individuals in the highest decile of PGS for depressive symptoms had over 5 times higher odds of being prescribed medication for comorbid anxiety and depression compared to those in the lowest decile. While results on a predominant role of depressive symptoms may have been biased by the size and heterogeneity of available data bases, they are consistent with the conclusion that genetic factors explain substantially more variation in comorbid anxiety and depression than anxiety or depression alone.
焦虑和抑郁常常同时出现，与单独出现时相比，会导致更差的健康结果。我们旨在确定共病焦虑和抑郁的遗传易感性是否大于焦虑或抑郁单独出现时的情况。对12792名基因分型双胞胎（年龄38 - 85岁）的数据进行了分析，其中包括1986对完全同卵双胞胎和1594对完全异卵双胞胎。结局指标为根据世界卫生组织解剖学治疗学化学分类系统（ATC）惯例开具的抗抑郁药和抗焦虑药处方，用于共病焦虑和抑郁（n = 1028）、仅焦虑（n = 718）以及仅抑郁（n = 484）的情况。使用双胞胎模型估计每种结局的遗传度，并通过抑郁症状、焦虑和其他40个性状的多基因评分（PGS）评估常见基因变异的影响。共病焦虑和抑郁的遗传度为79%，而仅焦虑的遗传度为41%，仅抑郁的遗传度为50%。抑郁症状的PGS同样比其他结局指标能预测共病焦虑和抑郁中更多的变异（每标准差PGS调整后的优势比 = 1.53，95%置信区间 = 1.43 - 1.63；ΔR = 0.031，ΔAUC = 0.044），当根据国际疾病分类（ICD）诊断定义共病焦虑和抑郁时，结果几乎相同（每标准差PGS调整后的优势比 = 1.70，95%置信区间 = 1.53 - 1.90；ΔR = 0.036，ΔAUC = 0.051）。抑郁症状PGS处于最高十分位数的个体被开具共病焦虑和抑郁药物处方的几率是处于最低十分位数个体的5倍多。虽然关于抑郁症状起主要作用的结果可能因现有数据库的规模和异质性而存在偏差，但它们与以下结论一致：遗传因素在共病焦虑和抑郁中解释的变异比焦虑或抑郁单独出现时要多得多。
