Citalopram and sertraline exposure compromises embryonic bone development

Fraher, D., Hodge, J. M., Collier, F. M., McMillan, J. S., Kennedy, R. L., Ellis, M., Nicholson, G. C., Walder, K., Dodd, S., Berk, M., Pasco, J. A., Williams, L. J. and Gibert, Y. (2016) Citalopram and sertraline exposure compromises embryonic bone development. Molecular Psychiatry, 21 5: 656-664. doi:10.1038/mp.2015.135

Author Fraher, D.
Hodge, J. M.
Collier, F. M.
McMillan, J. S.
Kennedy, R. L.
Ellis, M.
Nicholson, G. C.
Walder, K.
Dodd, S.
Berk, M.
Pasco, J. A.
Williams, L. J.
Gibert, Y.
Title Citalopram and sertraline exposure compromises embryonic bone development
Journal name Molecular Psychiatry   Check publisher's open access policy
ISSN 1476-5578
Publication date 2016-05-01
Year available 2016
Sub-type Article (original research)
DOI 10.1038/mp.2015.135
Open Access Status Not Open Access
Volume 21
Issue 5
Start page 656
End page 664
Total pages 9
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Formatted abstract
Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed treatments for depression and, as a class of drugs, are among the most used medications in the world. Concern regarding possible effects of SSRI treatment on fetal development has arisen recently as studies have suggested a link between maternal SSRI use and an increase in birth defects such as persistent pulmonary hypertension, seizures and craniosynostosis. Furthermore, SSRI exposure in adults is associated with decreased bone mineral density and increased fracture risk, and serotonin receptors are expressed in human osteoblasts and osteoclasts. To determine possible effects of SSRI exposure on developing bone, we treated both zebrafish, during embryonic development, and human mesenchymal stem cells (MSCs), during differentiation into osteoblasts, with the two most prescribed SSRIs, citalopram and sertraline. SSRI treatment in zebrafish decreased bone mineralization, visualized by alizarin red staining and decreased the expression of mature osteoblast-specific markers during embryogenesis. Furthermore, we showed that this inhibition was not associated with increased apoptosis. In differentiating human MSCs, we observed a decrease in osteoblast activity that was associated with a decrease in expression of the osteoblast-specific genes Runx2, Sparc and Spp1, measured with quantitative real-time PCR (qRT-PCR). Similar to the developing zebrafish, no increase in expression of the apoptotic marker Caspase 3 was observed. Therefore, we propose that SSRIs inhibit bone development by affecting osteoblast maturation during embryonic development and MSC differentiation. These results highlight the need to further investigate the risks of SSRI use during pregnancy in exposing unborn babies to potential skeletal abnormalities.
Keyword Biochemistry & Molecular Biology
Biochemistry & Molecular Biology
Neurosciences & Neurology
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 1059660
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Admin Only - School of Medicine
School of Medicine Publications
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