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, vol. 21, pp. 656-664.

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Title Citalopram and sertraline exposure compromises embryonic bone development
Author(s) Fraher, D.
Hodge, J. M.
Collier, F. M.ORCID iD for Collier, F. M.
McMillan, J. S.
Kennedy, R. L.
Ellis, M.ORCID iD for Ellis, M.
Nicholson, G. C.
Walder, K.ORCID iD for Walder, K.
Dodd, S.ORCID iD for Dodd, S.
Berk, M.ORCID iD for Berk, M.
Pasco, J. A.ORCID iD for Pasco, J. A.
Williams, L. J.ORCID iD for Williams, L. J.
Gibert, Y.
Journal name Molecular psychiatry
Volume number 21
Start page 656
End page 664
Total pages 9
Publisher Nature Publishing Group
Place of publication London, Eng.
Publication date 2016
ISSN 1476-5578
Summary 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.Molecular Psychiatry advance online publication, 8 September 2015; doi:10.1038/mp.2015.135.
Language eng
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 929999 Health not elsewhere classified
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2016, Nature Publishing Group
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