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Citalopram and sertraline exposure compromises embryonic bone development

Molecular Psychiatry volume 21, pages 656–664 (2016)Cite this article

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An Erratum to this article was published on 01 December 2015

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.

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Acknowledgements

We thank the staff members of the Deakin University zebrafish facility for providing excellent husbandry care. YG is supported by funding from the Molecular and Medical Research Strategic Centre at Deakin University. MB is supported by a NHMRC Senior Principal Research Fellowship (1059660). LJW is supported by a NHMRC Career development Fellowship (1064272).

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Author notes

  1. D Fraher and J M Hodge: These authors contributed equally to this work.

  2. L J Williams and Y Gibert: These authors are co-senior authors.

Authors and Affiliations

  1. Metabolic Genetic Diseases Laboratory, Metabolic Research Unit, School of Medicine, Deakin University, Geelong, VIC, Australia

    D Fraher, M Ellis, K Walder & Y Gibert

  2. IMPACT and MMR Strategic Research Centres, School of Medicine, Deakin University, Geelong, VIC, Australia

    D Fraher, J M Hodge, F M Collier, M Ellis, K Walder, S Dodd, M Berk, J A Pasco, L J Williams & Y Gibert

  3. Barwon Biomedical Research, University Hospital, Geelong, VIC, Australia

    J M Hodge, J S McMillan, R L Kennedy & G C Nicholson

  4. Department of Psychiatry, Orygen, The National Centre of Excellence in Youth Mental Health and the Centre for Youth Mental Health, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia

    M Berk

  5. Department of Medicine, Northwest Academic Centre, The University of Melbourne, St Albans, VIC, Australia

    J A Pasco

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Correspondence to Y Gibert.

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Fraher, D., Hodge, J., Collier, F. et al. Citalopram and sertraline exposure compromises embryonic bone development. Mol Psychiatry 21, 656–664 (2016). https://doi.org/10.1038/mp.2015.135

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