SSRI Drug Exposure in Utero aFfects Development of the Palate in a Murine Model

Objectives: Antidepressants, specifically Selective Serotonin Re-uptake Inhibitors (SSRIs), that alter serotonin metabolism are currently the most prescribed drugs for the treatment of depression. There is some evidence to suggest these drugs contribute to birth defects, specifically craniofacial malformations. As jaw development is often altered in craniofacial birth defects, the most common birth defects seen clinically, the purpose of this study was to interrogate the effects of in utero SSRI exposure in a preclinical model of maxillary, palatal, and dental development. We hypothesized that in utero exposure to SSRI would affect dimensions of both the palate and maxillary molars of murine mice models.
Methods: To test this hypothesis, wild type C57BL6 mice were used to produce litters that were exposed in utero to an SSRI, Citalopram (500 µg/day). Murine skulls from P15 pups were subjected to μCT and images were obtained using a SkyScan 1176 (Bruker Kartuizerseg 3B, 2550 Kontich, Belgium) scanner. Scans were analyzed using AnalyzePro for change in shape and composition of the facial complex using cephalometric analyses.
Results: Results suggest SSRI exposure resulted in offspring having significantly shorter (p=0.017) and narrower palates (p=0.013) using multiple measures compared to control untreated pups. Upon examination of dentition there was minimal impact on molar length and width (p>0.05).
Conclusions: These resulting craniofacial morphologies have been shown to increase risk of malocclusion, sleep apnea and difficulties nursing in humans. The results of this study reveal SSRI exposure may interrupt maxillary and more specifically palatal growth in a model of development giving insight into the expectation that children exposed to SSRIs may require orthodontic intervention.