Neurology Central

Is a polygenic predictor of antidepressant response a possibility?

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The hypothesis that antidepressant response has a relevant genetic component was initially suggested by the observation that this phenotype clusters in families [1]. Since the first pharmacogenetic studies investigated antidepressant efficacy in the 1990s, methodological innovations have been outstanding from a qualitative and quantitative point of view, moving from the analysis of few polymorphisms to millions and from statistics focused on single variants to multimarker tests. Candidate gene studies have been focused on a limited number of polymorphisms in genes that were thought to play a pivotal role in antidepressant mechanisms of action. The selection of candidate genes was usually based on data from preclinical studies, thus the risk of false positive findings was reduced by increasing the pretest probability, but the limitations of this approach became evident as antidepressant response proved to be a highly polygenic trait [2].
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