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. Attached Files Name Description MIMEType Size Downloads Title Citalopram and sertraline exposure compromises embryonic bone development Author(s) Fraher, D. Hodge, J. M. Collier, F. M. orcid.org/0000-0002-5438-480X McMillan, J. S. Kennedy, R. L. Ellis, M. orcid.org/0000-0001-9790-5735 Nicholson, G. C. Walder, K. orcid.org/0000-0002-6758-4763 Dodd, S. orcid.org/0000-0002-7918-4636 Berk, M. orcid.org/0000-0002-5554-6946 Pasco, J. A. orcid.org/0000-0002-8968-4714 Williams, L. J. orcid.org/0000-0002-1377-1272 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 Persistent URL http://hdl.handle.net/10536/DRO/DU:30078287 Document type: Journal Article Collections: Faculty of Health School of Medicine Related Links Link Description Connect to published version Go to link with your DU access privileges     Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved. Versions Version Filter Type Thu, 10 Sep 2015, 14:10:40 EST Fri, 11 Sep 2015, 05:01:01 EST Sat, 12 Sep 2015, 06:27:25 EST Mon, 14 Sep 2015, 10:33:39 EST Mon, 14 Sep 2015, 10:34:40 EST Mon, 12 Oct 2015, 16:15:30 EST Mon, 13 Jun 2016, 15:55:16 EST Mon, 13 Jun 2016, 15:56:03 EST Mon, 18 Jul 2016, 15:44:07 EST Filtered Full Citation counts:   Cited 14 times in TR Web of Science Cited 12 times in Scopus Search Google Scholar Access Statistics: 736 Abstract Views, 2 File Downloads  -  Detailed Statistics Created: Thu, 10 Sep 2015, 14:10:40 EST

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