Li Yuchen, Sjölander Arvid, Song Huan, Cnattingius Sven, Fang Fang, Yang Qian, Fernández de la Cruz Lorena, Mataix-Cols David, Brander Gustaf, Li Jiong, Zhang Wei, Fall Katja, D'Onofrio Brian M, Almqvist Catarina, Lichtenstein Paul, Valdimarsdóttir Unnur A, Lu Donghao
Mental Health Center, West China Hospital of Sichuan University, Chengdu, China.
West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China.
Mol Psychiatry. 2022 Mar;27(3):1712-1719. doi: 10.1038/s41380-021-01406-5. Epub 2022 Jan 1.
Little is known about the contribution of pregnancy-related parental and perinatal factors to the development of stress-related disorders. We aimed to investigate whether parental/perinatal adversities entail higher risks of stress-related disorders in the offspring, later in life, by accounting for genetic and early environmental factors. Based on the nationwide Swedish registers, we conducted a population-based cohort study of 3,435,747 singleton births (of which 2,554,235 were full siblings), born 1973-2008 and survived through the age of 5 years. Using both population- and sibling designs, we employed Cox regression to assess the association between parental and perinatal factors with subsequent risk of stress-related disorders. We identified 55,511 individuals diagnosed with stress-related disorders in the population analysis and 37,433 in the sibling analysis. In the population-based analysis we observed increased risks of stress-related disorders among offspring of maternal/paternal age <25, single mothers, parity ≥4, mothers with BMI ≥ 25 or maternal smoking in early pregnancy, gestational diabetes, and offspring born moderately preterm (GA 32-36 weeks), or small-for-gestational-age. These associations were significantly attenuated toward null in the sibling analysis. Cesarean-section was weakly associated with offspring stress-related disorders in population [hazard ratio (HR) 1.09, 95% confidence interval (CI) 1.06-1.12] and sibling analyses (HR 1.10, 95% CI 1.02-1.20). Our findings suggest that most of the observed associations between parental and perinatal factors and risk of stress-related disorders in the population analysis are driven by shared familial environment or genetics, and underscore the importance of family designs in epidemiological studies on the etiology of psychiatric disorders.
关于与妊娠相关的父母及围产期因素对应激相关障碍发展的影响，我们所知甚少。我们旨在通过考虑遗传和早期环境因素，调查父母/围产期逆境是否会使后代在生命后期患应激相关障碍的风险更高。基于瑞典全国登记册，我们对1973年至2008年出生且存活至5岁的3435747例单胎出生婴儿（其中2554235例为全同胞）进行了一项基于人群的队列研究。我们采用人群设计和同胞设计，运用Cox回归评估父母及围产期因素与随后患应激相关障碍风险之间的关联。在人群分析中，我们确定了55511例被诊断为应激相关障碍的个体，在同胞分析中为37433例。在基于人群的分析中，我们观察到母亲/父亲年龄<25岁、单身母亲、产次≥4次、BMI≥25的母亲或孕早期吸烟的母亲、妊娠期糖尿病以及中度早产（孕龄32 - 36周）或小于胎龄儿出生的后代患应激相关障碍的风险增加。在同胞分析中，这些关联显著减弱至无效。剖宫产与人群分析中后代应激相关障碍的关联较弱[风险比（HR）1.09，95%置信区间（CI）1.06 - 1.12]，在同胞分析中为（HR 1.10，95% CI 1.02 - 1.20）。我们的研究结果表明，在人群分析中观察到的父母及围产期因素与应激相关障碍风险之间的大多数关联是由共享的家庭环境或基因驱动的，并强调了家庭设计在精神障碍病因学流行病学研究中的重要性。
