Sánchez Natalia, Juárez-Balarezo Jesús, Olhaberry Marcia, González-Oneto Humberto, Muzard Antonia, Mardonez María Jesús, Franco Pamela, Barrera Felipe, Gaete Marcia
Department of Anatomy, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
Department of Psychology, Pontificia Universidad Católica de Chile, Santiago, Chile.
Front Cell Dev Biol. 2021 Aug 12;9:632766. doi: 10.3389/fcell.2021.632766. eCollection 2021.
Depression is a common and debilitating mood disorder that increases in prevalence during pregnancy. Worldwide, 7 to 12% of pregnant women experience depression, in which the associated risk factors include socio-demographic, psychological, and socioeconomic variables. Maternal depression could have psychological, anatomical, and physiological consequences in the newborn. Depression has been related to a downregulation in serotonin levels in the brain. Accordingly, the most commonly prescribed pharmacotherapy is based on selective serotonin reuptake inhibitors (SSRIs), which increase local serotonin concentration. Even though the use of SSRIs has few adverse effects compared with other antidepressants, altering serotonin levels has been associated with the advent of anatomical and physiological changes , leading to defects in craniofacial development, including craniosynostosis, cleft palate, and dental defects. Migration and proliferation of neural crest cells, which contribute to the formation of bone, cartilage, palate, teeth, and salivary glands in the craniofacial region, are regulated by serotonin. Specifically, craniofacial progenitor cells are affected by serotonin levels, producing a misbalance between their proliferation and differentiation. Thus, it is possible to hypothesize that craniofacial development will be affected by the changes in serotonin levels, happening during maternal depression or after the use of SSRIs, which cross the placental barrier, increasing the risk of craniofacial defects. In this review, we provide a synthesis of the current research on depression and the use of SSRI during pregnancy, and how this could be related to craniofacial defects using an interdisciplinary perspective integrating psychological, clinical, and developmental biology perspectives. We discuss the mechanisms by which serotonin could influence craniofacial development and stem/progenitor cells, proposing some transcription factors as mediators of serotonin signaling, and craniofacial stem/progenitor cell biology. We finally highlight the importance of non-pharmacological therapies for depression on fertile and pregnant women, and provide an individual analysis of the risk-benefit balance for the use of antidepressants during pregnancy.
抑郁症是一种常见且使人衰弱的情绪障碍，在孕期患病率会升高。在全球范围内，7%至12%的孕妇会经历抑郁症，其相关风险因素包括社会人口统计学、心理和社会经济变量。母亲患抑郁症可能会给新生儿带来心理、解剖学和生理学方面的后果。抑郁症与大脑中血清素水平下调有关。因此，最常用的药物治疗是基于选择性血清素再摄取抑制剂（SSRI），它会增加局部血清素浓度。尽管与其他抗抑郁药相比，使用SSRI的不良反应较少，但改变血清素水平与解剖学和生理学变化的出现有关，会导致颅面发育缺陷，包括颅缝早闭、腭裂和牙齿缺陷。血清素可调节神经嵴细胞的迁移和增殖，而神经嵴细胞有助于颅面部区域骨骼、软骨、腭、牙齿和唾液腺的形成。具体而言，颅面祖细胞会受到血清素水平的影响，导致其增殖和分化失衡。因此，可以推测，在母亲患抑郁症期间或使用能穿过胎盘屏障的SSRI后，血清素水平的变化会影响颅面发育，增加颅面缺陷的风险。在本综述中，我们综合了当前关于孕期抑郁症及SSRI使用的研究，以及如何从整合心理学、临床和发育生物学观点的跨学科视角将其与颅面缺陷联系起来。我们讨论了血清素影响颅面发育和干/祖细胞的机制，提出一些转录因子作为血清素信号传导的介质，以及颅面干/祖细胞生物学。我们最后强调了针对育龄和怀孕女性抑郁症的非药物疗法的重要性，并对孕期使用抗抑郁药的风险效益平衡进行了个体化分析。
