Department of Biomedical Education & Anatomy, The Ohio State University College of Medicine, Columbus, Ohio, USA.
Department of Anthropology, The Pennsylvania State University, State College, Pennsylvania, USA.
Orthod Craniofac Res. 2023 Aug;26(3):415-424. doi: 10.1111/ocr.12624. Epub 2022 Dec 19.
Antidepressants, specifically Selective Serotonin Re-uptake Inhibitors (SSRIs), that alter serotonin metabolism are currently the most commonly prescribed drugs for the treatment of depression. There is some evidence to suggest these drugs contribute to birth defects. As jaw development is often altered in craniofacial birth defects, the purpose of this study was to interrogate the effects of in utero SSRI exposure in a preclinical model of mandible development.
Wild-type C57BL6 mice were used to produce litters that were exposed in utero to an SSRI, Citalopram (500 μg/day). Murine mandibles from P15 pups were analysed for a change in shape and composition.
Analysis indicated an overall shape change with total mandibular length and ramus height being shorter in exposed pups as compared to controls. Histomorphometric analysis revealed that first molar length was longer in exposed pups while third molar length was shorter in exposed as compared to control. Histological investigation of molars and surrounding periodontium revealed no change in collagen content of the molar in exposed pups, some alteration in collagen composition in the periodontium, increased alkaline phosphatase in molars and periodontium and decreased mesenchymal cell marker presence in exposed mandibles.
The results of this study reveal SSRI exposure may interrupt mandible growth as well as overall dental maturation in a model of development giving insight into the expectation that children exposed to SSRIs may require orthodontic intervention.
抗抑郁药，特别是选择性 5-羟色胺再摄取抑制剂（SSRIs），可改变 5-羟色胺代谢，目前是治疗抑郁症最常用的药物。有证据表明这些药物会导致出生缺陷。由于颅面出生缺陷常改变下颌的发育，本研究的目的是在一个下颌发育的临床前模型中检测宫内 SSRI 暴露的影响。
使用野生型 C57BL6 小鼠产生暴露于 SSRI 西酞普兰（500μg/天）的宫内胎鼠。对 P15 幼鼠的鼠下颌进行形状和成分分析。
分析表明，与对照组相比，暴露组的总下颌长度和支高度更短，整体形状发生变化。组织形态计量学分析显示，暴露组的第一磨牙长度更长，而第三磨牙长度更短。对磨牙和周围牙周组织的组织学研究表明，暴露组的磨牙胶原含量没有变化，牙周组织的胶原组成发生了一些改变，磨牙和牙周组织中的碱性磷酸酶增加，暴露组下颌间的间充质细胞标记物减少。
本研究结果表明，SSRI 暴露可能会中断下颌生长以及发育模型中的整体牙齿成熟，这深入了解了儿童暴露于 SSRIs 可能需要正畸干预的预期。
