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New genetic markers predict antidepressant efficacy

04 May 2010

Research led by the Medical Research Council Social Genetic and Developmental Psychiatry Centre at the Institute of Psychiatry King’s College London, published in the American Journal of Psychiatry this month, has identified new genetic markers for response to antidepressants.

Up to one in five people at some point in their lives suffer from an episode of depression severe enough to warrant antidepressant treatment. However, at present, doctors don’t have enough information to know how well patients will respond to one antidepressant over another. This means patients may not get better on the first treatment they try or they may develop side-effects.

The research is part of the GENDEP study which aims to identify genetic variants underlying the considerable individual differences in response to antidepressant treatment so treatment can be tailored to the individual.

The authors searched the whole genetic make up of 706 people with depression. They looked for genetic variants that can predict how much their depression improves over 12 weeks of treatment. The particpants were treated with one of two antidepressants, nortriptyline or escitalopram.

This genome scan brought some unexpected results. A gene for uronyl 2-sulphotransferase predicted response to nortriptyline. This gene was not previously suspected to determine antidepressant response, but it is known to be essential for the creation of new nervous cells in the brain (neurogenesis), a process that may be important in the therapeutic action of some antidepressants.

Response to escitalopram was best predicted by a marker in the interleukin-11 (IL11) gene. This in turn points to an interface between inflammation and serotonin brain signalling and may start a new stream of research that will uncover why some individuals respond to serotonergic prozac-type antidepressants better than others.

Principal Investigator Professor Peter McGuffin said: “These results suggest that efficacy of antidepressants can be predicted by genetic markers other than the ones that are already known about, such as the serotonin transporter.

He continues: 'Such insights can advance understanding of the biological mechanisms responsible for an antidepressants being effective, which is important for the development of new and better treatments for depression. However, we first need to see any of these findings replicated in new samples before we can recommend their use for personalized medicine. We are working on this in a new EC-funded project, the NEWMEDS.'

The European Commission (EC) and the Medical Research Council ( MRC) funded this  four  year project, involving scientists, clinicians, and industrial partners from ten EU countries.

Genome-Wide Pharmacogenetics of Antidepressant Response in the GENDEP Project is published in the American Journal of Psychiatry can be found here: The authors are: Uher R, Perroud N, Ng MY, Hauser J, Henigsberg N, Maier W, Mors O, Placentino A, Rietschel M, Souery D, Zagar T, Czerski PM, Jerman B, Larsen ER, Schulze TG, Zobel A, Cohen-Woods S, Pirlo K, Butler AW, Muglia P, Barnes MR, Lathrop M, Farmer A, Breen G, Aitchison KJ, Craig I, Lewis CM, McGuffin P.

Further details on NEWMEDS can be found here:



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