SLC6A2 and SLC6A4 Variants interact with Venlafaxine Serum Concentrations to Influence Therapy Outcome

Genetic variation underlies both the response to antidepressant treatment and the occurrence of side effects. Over the past two decades, a number of pharmacogenetic variants, among these the SCL6A4, BDNF, FKBP5, GNB3, GRIK4, and ABCB1 genes, have come to the forefront in this regard. However, small effects sizes, mixed results in independent samples, and conflicting meta-analyses results led to inherent difficulties in the field of pharmacogenetics translating these findings into clinical practice. Nearly all antidepressant pharmacogenetic variants have potentially pleiotropic effects in which they are associated with major depressive disorder, intermediate phenotypes involved in emotional processes, and brain areas affected by antidepressant treatment. The purpose of this article is to provide a comprehensive review of the advances made in the field of pharmacogenetics of antidepressant efficacy and side effects, imaging findings of antidepressant response, and the latest results in the expanding field of imaging-pharmacogenetics studies. We suggest there is mounting evidence that genetic factors exert their impact on treatment response by influencing brain structural and functional changes during antidepressant treatment, and combining neuroimaging and genetic methods may be a more powerful way to detect biological mechanisms of response than either method alone. The most promising imaging-pharmacogenetics findings exist for the SCL6A4 gene, with converging associations with antidepressant response, frontolimbic predictors of affective symptoms, and normalization of frontolimbic activity following antidepressant treatment. More research is required before imaging-pharmacogenetics informed personalized medicine can be applied to antidepressant treatment; nevertheless, inroads have been made towards assessing genetic and neuroanatomical liability and potential clinical application.

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Drug development

Raynaud¹

2020

Metabolomics for Biomedical Research

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SLC6A2 and SLC6A4 Variants interact with Venlafaxine Serum Concentrations to Influence Therapy Outcome

Abstract: The observed association is consistent with findings of some previous studies, whereas others showed differing results highlighting the need for further investigations.

Cited by 5 publications

References 34 publications

Genetic Factors Underlying Treatment Resistance in Psychiatry

Genetic Factors Underlying Treatment Resistance in Psychiatry

Pharmacogenetics and Imaging–Pharmacogenetics of Antidepressant Response: Towards Translational Strategies

Drug development

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