Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore.
The N.1 Institute for Health, National University of Singapore, Singapore, Singapore.
Transl Psychiatry. 2021 Mar 15;11(1):170. doi: 10.1038/s41398-021-01292-z.
Canonical transforming growth factor-beta (TGF-β) signaling exerts neuroprotection and influences memory formation and synaptic plasticity. It has been considered as a new target for the prevention and treatment of depression. This study aimed to examine its modulatory role in linking prenatal maternal depressive symptoms and the amygdala volumes from birth to 6 years of age. We included mother-child dyads (birth: n = 161; 4.5 years: n = 131; 6 years: n = 162) and acquired structural brain images of children at these three time points. Perinatal maternal depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS) questionnaire to mothers at 26 weeks of pregnancy and 3 months postpartum. Our findings showed that the genetic variants of TGF-β type I transmembrane receptor (TGF-βRI) modulated the association between prenatal maternal depressive symptoms and the amygdala volume consistently from birth to 6 years of age despite a trend of significance at 4.5 years of age. Children with a lower gene expression score (GES) of TGF-βRI exhibited larger amygdala volumes in relation to greater prenatal maternal depressive symptoms. Moreover, children with a lower GES of the TGF-β type II transmembrane receptor (TGF-βRII), Smad4, and Smad7 showed larger amygdala volumes at 6 years of age in relation to greater prenatal maternal depressive symptoms. These findings support the involvement of the canonical TGF-β signaling pathway in the brain development of children in the context of in utero maternal environment. Such involvement is age-dependent.
经典转化生长因子-β（TGF-β）信号发挥神经保护作用，并影响记忆形成和突触可塑性。它已被认为是预防和治疗抑郁症的新靶点。本研究旨在探讨其在连接产前母体抑郁症状和从出生到 6 岁的杏仁核体积中的调节作用。我们纳入了母婴对子（出生时：n=161；4.5 岁：n=131；6 岁：n=162），并在这三个时间点获得了儿童的结构脑图像。使用爱丁堡产后抑郁量表（EPDS）问卷在妊娠 26 周和产后 3 个月时评估围产期母体抑郁症状。我们的研究结果表明，TGF-β Ⅰ型跨膜受体（TGF-βRI）的遗传变异体从出生到 6 岁持续调节产前母体抑郁症状与杏仁核体积之间的关联，尽管在 4.5 岁时有显著趋势。TGF-βRI 的基因表达评分（GES）较低的儿童，与母体产前抑郁症状相关，杏仁核体积较大。此外，TGF-β Ⅱ型跨膜受体（TGF-βRII）、Smad4 和 Smad7 的 GES 较低的儿童，与母体产前抑郁症状相关，6 岁时杏仁核体积较大。这些发现支持经典 TGF-β 信号通路在子宫内母体环境背景下儿童大脑发育中的作用。这种参与是年龄依赖性的。
