Abstract
We investigated variants associated with treatment response in depressed patients treated with either the antidepressant duloxetine or placebo using a genome-wide approach. Our sample (N=391) included individuals aged 18–75 years, diagnosed with major depressive disorder and treated with either duloxetine or placebo for up to 8 weeks. We conducted genome-wide associations for treatment response as operationalized by percentage change in Montgomery–Åsberg Depression Rating Scale score from baseline, as well as mixed models analyses across five time points. In the placebo-treated subsample (N=205), we observed a genome-wide association with rs76767803 (β=0.69, P=1.25 × 10−8) upstream of STAC1. STAC1 rs76767803 was also associated with response using mixed model analysis (χ2=3.95; P=0.001). In the duloxetine-treated subsample (N=186), we observed suggestive associations with ZNF385D (rs4261893; β=−0.46, P=1.55 × 10−5), NCAM1 (rs2303377; β=0.45, P=1.76 × 10−5) and MLL5 (rs117986340; β=0.91, P=3.04 × 10−5). Our findings suggest that a variant upstream of STAC1 is associated with placebo response, which might have implications for treatment optimization, clinical trial design and drug development.
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Acknowledgements
This research was conducted with the support of the Ontario Brain Institute, an independent non-profit corporation, funded partially by the Ontario government. The opinions, results and conclusions are those of the authors and no endorsement by the Ontario Brain Institute is intended or should be inferred. This study was part of a Canadian Biomarker Integration Network in Depression (CAN-BIND) project. The authors wish to acknowledge the CAN-BIND team listed here: www.canbind.ca/our-team. MM is supported by a CIHR postdoctoral fellowship; VSM is supported by an OMHF doctoral studentship and a trainee fellowship from the CIHR-STAGE program, and DJM is supported by the Joanne Murphy Professorship.
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Maciukiewicz, M., Marshe, V., Tiwari, A. et al. Genome-wide association studies of placebo and duloxetine response in major depressive disorder. Pharmacogenomics J 18, 406–412 (2018). https://doi.org/10.1038/tpj.2017.29
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DOI: https://doi.org/10.1038/tpj.2017.29