Maternal polycystic ovary syndrome and risk of neuropsychiatric disorders in offspring: prenatal androgen exposure or genetic confounding?
Maternal polycystic ovary syndrome and risk of neuropsychiatric disorders in offspring: prenatal androgen exposure or genetic confounding?
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DOI：
10.1017/s0033291719000424
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发表时间：
2020-03-01
影响因子：
6.9
通讯作者：
Rosenqvist, Mina A.
中科院分区：
文献类型：
--
作者：
Cesta, Carolyn E.;Oberg, Anna S.;Rosenqvist, Mina A.
研究背景母体多囊卵巢综合征（PCOS）已被提出作为研究产前雄激素暴露在神经精神疾病发展中的作用的模型。然而，患有PCOS的妇女有更高的发展精神疾病的风险，并且以前的研究可能受到遗传影响的混淆。MethodsA Swedish nationwide register-based cohort study被进行，以解开产前雄激素暴露对母亲PCOS和后代注意力缺陷/多动障碍（ADHD），自闭症谱系障碍（ASD），以及图雷特氏症和慢性抽动障碍（TD/CTD）。将暴露于PCOS的后代（n = 21 280）与不相关的未暴露于PCOS的后代（n = 200 816）和未暴露于PCOS的表亲（n = 17 295）进行比较。协会估计分层考克斯回归models. ResultsPCOS暴露的后代被诊断为ADHD，ASD，TD/CTD的风险增加与无关的PCOS未暴露的后代。女孩ADHD和ASD的相关性更强，但TD/CTD的相关性不强[ADHD：校正风险比（aHR）= 1.61（95%置信区间（CI）1.31-1.99），ASD：aHR = 2.02 ADHD：aHR = 1.37（95%CI 1.19-1.57），ASD：aHR = 1.46（95%CI 1.21-1.76）。对于ADHD和ASD，aHRs的女孩更强的PCOS未暴露的堂兄弟相比，但略有衰减boy.ConclusionsEstimates是相似的，当占家族混杂（即遗传和环境因素共享的堂兄弟）和更强的女孩ADHD和ASD，可能表明产前雄激素暴露诉遗传因素的差异影响。这些结果加强了证据的一个潜在的因果关系的影响，产前雄激素暴露的发展男性占主导地位的神经精神疾病的女性后代与PCOS的妇女。
BackgroundMaternal polycystic ovary syndrome (PCOS) has been proposed as a model for investigating the role of prenatal androgen exposure in the development of neuropsychiatric disorders. However, women with PCOS are at higher risk of developing psychiatric conditions and previous studies are likely confounded by genetic influences.MethodsA Swedish nationwide register-based cohort study was conducted to disentangle the influence of prenatal androgen exposure from familial confounding in the association between maternal PCOS and offspring attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD), and Tourette's disorder and chronic tic disorders (TD/CTD). PCOS-exposed offspring (n = 21 280) were compared with unrelated PCOS-unexposed offspring (n = 200 816) and PCOS-unexposed cousins (n = 17 295). Associations were estimated with stratified Cox regression models.ResultsPCOS-exposed offspring had increased risk of being diagnosed with ADHD, ASD, and TD/CTD compared with unrelated PCOS-unexposed offspring. Associations were stronger in girls for ADHD and ASD but not TD/CTD [ADHD: adjusted hazard ratio (aHR) = 1.61 (95% confidence interval (CI) 1.31-1.99), ASD: aHR = 2.02 (95% CI 1.45-2.82)] than boys [ADHD: aHR = 1.37 (95% CI 1.19-1.57), ASD: aHR = 1.46 (95% CI 1.21-1.76)]. For ADHD and ASD, aHRs for girls were stronger when compared with PCOS-unexposed cousins, but slightly attenuated for boys.ConclusionsEstimates were similar when accounting for familial confounding (i.e. genetics and environmental factors shared by cousins) and stronger in girls for ADHD and ASD, potentially indicating a differential influence of prenatal androgen exposure v. genetic factors. These results strengthen evidence for a potential causal influence of prenatal androgen exposure on the development of male-predominant neuropsychiatric disorders in female offspring of women with PCOS.