Prediction of antidepressant treatment response - a pharmaco- and Imaging genetic contribution
Domschke, Katharina, Dannlowski, Udo, Ohrmann, Patricia, Hohoff, Christa, Deckert, Jürgen, Arolt, Volker, Suslow, Thomas, and Baune, Bernhard T. (2010) Prediction of antidepressant treatment response - a pharmaco- and Imaging genetic contribution. In: Biological Psychiatry (67), 3S-4S. From: 65th Annual Meeting of the Society of Biological Psychiatry, 20 - 22 May 2010, New Orleans, LA, USA.
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Background: In major depression, an increasing number of pharmacogenetic studies have examined association of antidepressant treatment response with variation in candidate genes. Given only few consistently reproducible findings, we attempted to further refine investigation of the clinical phenotype of depression in pharmacogenetic studies with particular attention to gender, melancholic and anxious depression as well as the intermediate phenotype of emotional processing.
Methods: In a sample of 256 Caucasian patients with Major Depression, candidate gene variants of the serotonergic, noradrenergic, NPY and endocannabinoid systems were investigated for their impact on antidepressant treatment response. A subsample of 35 patients was additionally scanned by means of fMRI at 3 T under visual presentation of emotional faces using an imaging genetics approach.
Results: The MAO-A VNTR and the COMT val158met variants were found to influence antidepressant treatment response specifically in female patients. The 5-HT1A -1019 C/G polymorphism was associated with treatment response in patients with melancholic, but not atypical depression. 5-HTTLPR, CNR1 rs1049353 and NPY rs16147 were observed to significantly impair treatment response particularly in anxious depression via altered brain activity in amygdala, prefrontal and striatal regions during processing of depression related emotional stimuli.
Conclusions: The present results suggest a significant impact of 5-HTT, 5-HT1A, MAO-A, COMT, CNR1 and NPY gene variants on antidepressant treatment response with differential effects regarding gender and clinical subtypes of melancholic and anxious depression, potentially mediated via distorted emotional processing in the limbic-frontal circuit. These findings point towards a network model of cellular (genetic) and circuit (brain network) factors contributing to antidepressant treatment success.
|Item Type:||Conference Item (Abstract / Summary)|
Biological Psychiatry Volume 67, Issue 9, Supplement (01 May 2010)
|Date Deposited:||11 May 2011 01:19|
|FoR Codes:||11 MEDICAL AND HEALTH SCIENCES > 1109 Neurosciences > 110999 Neurosciences not elsewhere classified @ 100%|
|SEO Codes:||92 HEALTH > 9204 Public Health (excl. Specific Population Health) > 920410 Mental Health @ 100%|
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