遗传和环境因素对内分泌代谢紊乱和抑郁症共病的影响：一项全国性瑞典同胞研究。
Genetic and Environmental Contribution to the Co-Occurrence of Endocrine-Metabolic Disorders and Depression: A Nationwide Swedish Study of Siblings.
机构信息
Janssen Pharmaceutical Companies of Johnson & Johnson, Solna, Sweden (Leone, Leval); Department of Medical Epidemiology and Biostatistics (Leone, Kuja-Halkola, Leval, Butwicka, Zhang, Liu, Larsson, Bergen) and Department of Molecular Medicine and Surgery (Skov), Karolinska Institutet, Solna, Sweden; Child and Adolescent Psychiatry Stockholm, Stockholm Health Care Services, Region Stockholm, Sweden (Butwicka); Department of Child Psychiatry, Medical University of Warsaw, Warsaw (Butwicka); Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland (Butwicka); Department of Medicine, Karlstad Central Hospital, Karlstad, Sweden (Skov); School of Medical Sciences, Örebro University, Örebro, Sweden (Larsson).
出版信息
Am J Psychiatry. 2022 Nov 1;179(11):824-832. doi: 10.1176/appi.ajp.21090954. Epub 2022 Sep 21.
OBJECTIVE
Depression is common in individuals with endocrine-metabolic disorders and vice versa, and a better understanding of the underlying factors contributing to the comorbidity of these disorders is needed. This study investigated the familial coaggregation of depression and endocrine-metabolic disorders and estimated the contribution of genetic and environmental factors to their co-occurrence.
METHODS
This population-based cohort study included 2.2 million individuals born in Sweden between 1973 and 1996, with follow-up through 2013. Participants were linked to their biological parents, allowing identification of full siblings, maternal half siblings, and paternal half siblings. Diagnoses of depression and endocrine-metabolic conditions were investigated, with the latter grouped into autoimmune disorders (autoimmune hypothyroidism, Graves' disease, and type 1 diabetes) and non-autoimmune disorders (type 2 diabetes, obesity, and polycystic ovary syndrome). Logistic regression and Cox regression were used to estimate the associations between endocrine-metabolic disorders and depression within the same individual and across siblings. Quantitative genetic modeling was performed to investigate the relative contribution of genetic and environmental influences.
RESULTS
Individuals with endocrine-metabolic disorders had a significantly higher risk of depression, with odds ratios ranging from 1.43 (95% CI=1.30, 1.57) for Graves' disease to 3.48 (95% CI=3.25, 3.72) for type 2 diabetes. Increased risks extended to full and half siblings. These correlations were mainly explained by shared genetic influences for non-autoimmune conditions, and by nonshared environmental factors for autoimmune disorders, especially for type 1 diabetes.
CONCLUSIONS
These findings provide phenotypic and etiological insights into the co-occurrence of depression and various endocrine-metabolic conditions, which could guide future research aiming at identifying pathophysiological mechanisms and intervention targets.
目的
抑郁症在患有内分泌代谢疾病的个体中很常见，反之亦然，需要更好地了解导致这些疾病同时发生的潜在因素。本研究调查了抑郁症和内分泌代谢疾病的家族聚集性，并估计了遗传和环境因素对它们共同发生的贡献。
方法
这是一项基于人群的队列研究，纳入了 1973 年至 1996 年间出生于瑞典的 220 万人，随访至 2013 年。参与者与他们的亲生父母相关联，从而可以识别出全同胞、生母半同胞和生父半同胞。调查了抑郁症和内分泌代谢疾病的诊断情况，将后者分为自身免疫性疾病（自身免疫性甲状腺功能减退症、格雷夫斯病和 1 型糖尿病）和非自身免疫性疾病（2 型糖尿病、肥胖症和多囊卵巢综合征）。使用逻辑回归和 Cox 回归来估计个体内部和兄弟姐妹之间内分泌代谢疾病与抑郁症之间的关联。进行定量遗传建模以调查遗传和环境影响的相对贡献。
结果
患有内分泌代谢疾病的个体患抑郁症的风险显著增加，比值比范围从格雷夫斯病的 1.43（95%CI=1.30,1.57）到 2 型糖尿病的 3.48（95%CI=3.25,3.72）。全同胞和半同胞也存在这种风险增加。这些相关性主要由非自身免疫疾病的共同遗传影响解释，而自身免疫疾病的非共享环境因素，尤其是 1 型糖尿病，主要解释了这种相关性。
结论
这些发现为抑郁症和各种内分泌代谢疾病同时发生提供了表型和病因学见解，这可能有助于指导未来旨在识别病理生理机制和干预靶点的研究。
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