Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Centre for Pharmacoepidemiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Psychol Med. 2020 Mar;50(4):616-624. doi: 10.1017/S0033291719000424. Epub 2019 Mar 12.
Maternal 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.
A 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.
PCOS-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.
Estimates 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.
多囊卵巢综合征（PCOS）的母体被认为是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 的女性患精神疾病的风险更高，并且之前的研究可能受到遗传影响的混杂。
进行了一项瑞典全国性基于登记的队列研究，以厘清产前雄激素暴露与母亲 PCOS 与后代注意力缺陷/多动障碍（ADHD）、自闭症谱系障碍（ASD）、妥瑞氏症和慢性抽动障碍（TD/CTD）之间关联中的家族性混杂影响。将 PCOS 暴露的后代（n=21280）与无相关 PCOS 未暴露的后代（n=200816）和无相关 PCOS 未暴露的表亲（n=17295）进行比较。使用分层 Cox 回归模型估计关联。
与无相关 PCOS 未暴露的后代相比，PCOS 暴露的后代被诊断为 ADHD、ASD 和 TD/CTD 的风险增加。这些关联在女孩中更强，与 ADHD 和 ASD 相关，但与 TD/CTD 无关[ADHD：调整后的危险比（aHR）=1.61（95%置信区间（CI）1.31-1.99），ASD：aHR=2.02（95%CI 1.45-2.82）]，而在男孩中则较弱[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，与无相关 PCOS 未暴露的表亲相比，女孩的 aHR 更强，但男孩的 aHR 略减弱。
当考虑家族性混杂因素（即表亲之间共享的遗传和环境因素）时，估计值相似，并且女孩的 ADHD 和 ASD 更强，这可能表明产前雄激素暴露与遗传因素对 PCOS 女性后代男性为主的神经精神疾病发展的影响存在差异。这些结果加强了产前雄激素暴露对 PCOS 女性后代男性为主的神经精神疾病发展的潜在因果影响的证据。
