Department of Clinical Psychopharmacology and Neurotoxicology, National Institute of Mental Health and Neurosciences, Bangalore, India (
J Clin Psychiatry. 2020 May 26;81(3):20f13463. doi: 10.4088/JCP.20f13463.
In observational studies, significant associations have often been identified between antidepressant drug prescription during pregnancy, on the one hand, and autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), on the other. Interpreting these associations is problematic because they are based on analyses that could not adjust for inadequately measured, unmeasured, and unknown confounds. Recent clinical data suggest that a genetic relationship exists between depression and neurodevelopmental disorders. A very recent study identified many genetic loci that were common to depression, ASD, and ADHD. These findings suggest the possibility that depression in a pregnant woman may predispose to neurodevelopmental disorders in offspring through shared genes and not through antidepressant use during pregnancy. Previous studies that significantly associated gestational exposure to antidepressants with adverse pregnancy outcomes could not adjust for genetic factors because they were unknown confounds at the time. Now that common risk loci have been identified, at least some of the unknown (genetic) confounds are no longer unknown; however, unless specifically examined in prospective studies, they will remain as unmeasured confounds that will continue to compromise the interpretation of study results. The possibility of confounding by inadequately measured, unmeasured, and unknown risk factors must therefore be considered before indicting antidepressant use during pregnancy in neurodevelopmental risks. In this context, the importance of genetic factors as unmeasured and unknown confounds must be acknowledged.
在观察性研究中，人们经常发现，一方面，孕妇在怀孕期间服用抗抑郁药，另一方面，与自闭症谱系障碍 (ASD) 和注意缺陷多动障碍 (ADHD) 之间存在显著关联。解释这些关联是有问题的，因为它们基于的分析无法调整未充分测量、未测量和未知的混杂因素。最近的临床数据表明，抑郁和神经发育障碍之间存在遗传关系。最近的一项研究确定了许多常见的遗传位点，这些遗传位点与抑郁、ASD 和 ADHD 都有关。这些发现表明，孕妇的抑郁可能通过共享基因而不是通过怀孕期间使用抗抑郁药使后代易患神经发育障碍。以前的研究发现，孕妇在妊娠期接触抗抑郁药与不良妊娠结局显著相关，但由于当时这些因素是未知的混杂因素，因此无法进行调整。由于现在已经确定了常见的风险位点，至少一些未知的（遗传）混杂因素不再是未知的；然而，除非在前瞻性研究中专门进行检查，否则它们仍将作为未测量的混杂因素，继续影响对研究结果的解释。因此，在指控孕妇在怀孕期间使用抗抑郁药会增加神经发育风险之前，必须考虑到未充分测量、未测量和未知风险因素造成的混杂的可能性。在这种情况下，必须承认遗传因素作为未测量和未知混杂因素的重要性。
