Pharmacoepidemiology and Drug Safety Research Group, Department of Pharmacy, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway.
PharmaTox Strategic Research Initiative, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway.
Transl Psychiatry. 2023 May 5;13(1):149. doi: 10.1038/s41398-023-02441-2.
Studies assessing associations between prenatal exposure to antidepressants, maternal depression, and offspring DNA methylation (DNAm) have been inconsistent. Here, we investigated whether prenatal exposure to citalopram or escitalopram ((es)citalopram) and maternal depression is associated with differences in DNAm. Then, we examined if there is an interaction effect of (es)citalopram exposure and DNAm on offspring neurodevelopmental outcomes. Finally, we investigated whether DNAm at birth correlates with neurodevelopmental trajectories in childhood. We analyzed DNAm in cord blood from the Norwegian Mother, Father and Child Cohort Study (MoBa) biobank. MoBa contains questionnaire data on maternal (es)citalopram use and depression during pregnancy and information about child neurodevelopmental outcomes assessed by internationally recognized psychometric tests. In addition, we retrieved ADHD diagnoses from the Norwegian Patient Registry and information on pregnancies from the Medical Birth Registry of Norway. In total, 958 newborn cord blood samples were divided into three groups: (1) prenatal (es)citalopram exposed (n = 306), (2) prenatal maternal depression exposed (n = 308), and (3) propensity score-selected controls (n = 344). Among children exposed to (es)citalopram, there were more ADHD diagnoses and symptoms and delayed communication and psychomotor development. We did not identify differential DNAm associated with (es)citalopram or depression, nor any interaction effects on neurodevelopmental outcomes throughout childhood. Trajectory modeling identified subgroups of children following similar developmental patterns. Some of these subgroups were enriched for children exposed to maternal depression, and some subgroups were associated with differences in DNAm at birth. Interestingly, several of the differentially methylated genes are involved in neuronal processes and development. These results suggest DNAm as a potential predictive molecular marker of later abnormal neurodevelopmental outcomes, but we cannot conclude whether DNAm links prenatal (es)citalopram exposure or maternal depression with child neurodevelopmental outcomes.
研究评估了产前暴露于抗抑郁药、产妇抑郁与后代 DNA 甲基化（DNAm）之间的关联，但结果并不一致。在这里，我们研究了产前暴露于西酞普兰或艾司西酞普兰（escitalopram）（es）和产妇抑郁是否与 DNAm 的差异有关。然后，我们检查了（es）西酞普兰暴露和 DNAm 对后代神经发育结果是否存在交互作用效应。最后，我们研究了出生时的 DNAm 是否与儿童期的神经发育轨迹相关。我们分析了挪威母亲、父亲和儿童队列研究（MoBa）生物库中的脐带血 DNAm。MoBa 包含了母亲在怀孕期间使用（es）西酞普兰和抑郁的问卷调查数据，以及通过国际公认的心理计量测试评估的儿童神经发育结果的信息。此外，我们从挪威患者登记处检索了 ADHD 诊断信息，并从挪威医学出生登记处检索了与怀孕相关的信息。总共 958 份新生儿脐带血样本分为三组：（1）产前（es）西酞普兰暴露组（n=306），（2）产前产妇抑郁暴露组（n=308），和（3）倾向评分匹配对照组（n=344）。在暴露于（es）西酞普兰的儿童中，ADHD 诊断和症状更多，且沟通和心理运动发育延迟。我们没有发现与（es）西酞普兰或抑郁相关的差异 DNAm，也没有发现整个儿童时期神经发育结果的交互作用效应。轨迹建模确定了遵循相似发育模式的儿童亚组。其中一些亚组中，产妇抑郁暴露的儿童比例较高，而一些亚组与出生时的 DNAm 差异相关。有趣的是，一些差异甲基化的基因涉及神经元过程和发育。这些结果表明 DNAm 可能是后期异常神经发育结果的潜在预测分子标志物，但我们不能得出结论，即 DNAm 是否与产前（es）西酞普兰暴露或产妇抑郁与儿童神经发育结果有关。
