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Pharmacogenetics of antidepressant response: A polygenic approach.

Abstract：

BACKGROUND:Major depressive disorder (MDD) has a high personal and socio-economic burden and >60% of patients fail to achieve remission with the first antidepressant. The biological mechanisms behind antidepressant response are only partially known but genetic factors play a relevant role. A combined predictor across genetic variants may be useful to investigate this complex trait. METHODS:Polygenic risk scores (PRS) were used to estimate multi-allelic contribution to: 1) antidepressant efficacy; 2) its overlap with MDD and schizophrenia. We constructed PRS and tested whether these predicted symptom improvement or remission from the GENDEP study (n=736) to the STAR*D study (n=1409) and vice-versa, including the whole sample or only patients treated with escitalopram or citalopram. Using summary statistics from Psychiatric Genomics Consortium for MDD and schizophrenia, we tested whether PRS from these disorders predicted symptom improvement in GENDEP, STAR*D, and five further studies (n=3756). RESULTS:No significant prediction of antidepressant efficacy was obtained from PRS in GENDEP/STAR*D but this analysis might have been underpowered. There was no evidence of overlap in the genetics of antidepressant response with either MDD or schizophrenia, either in individual studies or a meta-analysis. Stratifying by antidepressant did not alter the results. DISCUSSION:We identified no significant predictive effect using PRS between pharmacogenetic studies. The genetic liability to MDD or schizophrenia did not predict response to antidepressants, suggesting differences between the genetic component of depression and treatment response. Larger or more homogeneous studies will be necessary to obtain a polygenic predictor of antidepressant response.

journal_name

Prog Neuropsychopharmacol Biol Psychiatry

journal_title

Progress in neuro-psychopharmacology & biological psychiatry

authors

García-González J,Tansey KE,Hauser J,Henigsberg N,Maier W,Mors O,Placentino A,Rietschel M,Souery D,Žagar T,Czerski PM,Jerman B,Buttenschøn HN,Schulze TG,Zobel A,Farmer A,Aitchison KJ,Craig I,McGuffin P,Giupponi M,

doi

10.1016/j.pnpbp.2017.01.011

subject

Has Abstract

pub_date

2017-04-03 00:00:00

pages

128-134

eissn

0278-5846

issn

1878-4216

pii

S0278-5846(16)30438-9

journal_volume

75

pub_type

杂志文章

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