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Systems genetics analysis of pharmacogenomics variation during antidepressant treatment

The Pharmacogenomics Journal volume 18, pages 144–152 (2018)Cite this article

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Abstract

Selective serotonin reuptake inhibitors (SSRIs) are the most widely used antidepressants, but the efficacy of the treatment varies significantly among individuals. It is believed that complex genetic mechanisms play a part in this variation. We have used a network based approach to unravel the involved genetic components. Moreover, we investigated the potential difference in the genetic interaction networks underlying SSRI treatment response over time. We found four hub genes (ASCC3, PPARGC1B, SCHIP1 and TMTC2) with different connectivity in the initial SSRI treatment period (baseline to week 4) compared with the subsequent period (4–8 weeks after initiation), suggesting that different genetic networks are important at different times during SSRI treatment. The strongest interactions in the initial SSRI treatment period involved genes encoding transcriptional factors, and in the subsequent period genes involved in calcium homeostasis. In conclusion, we suggest a difference in genetic interaction networks between initial and subsequent SSRI response.

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Acknowledgements

We would like to thank the Mayo Clinic for allowing us access to the PGRN-SSRI Pharmacogenomics trail DNA samples through dbGaP. This study was funded by a postdoctoral grant from the Mental Health Services of the Capital Region of Denmark.

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Authors and Affiliations

  1. Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Capital Region of Denmark, Roskilde, Denmark

    M B Madsen & H B Rasmussen

  2. iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark

    M B Madsen & H B Rasmussen

  3. Department of Large Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark

    L J A Kogelman & H N Kadarmideen

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  1. M B Madsen
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Madsen, M., Kogelman, L., Kadarmideen, H. et al. Systems genetics analysis of pharmacogenomics variation during antidepressant treatment. Pharmacogenomics J 18, 144–152 (2018). https://doi.org/10.1038/tpj.2016.68

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