Genetic predictors of response to antidepressants in the GENDEP project

Uher, Rudolf; Huezo-Diaz, Patricia; Perroud, Nader; Smith, Rebecca; Rietschel, Marcella; Mors, Ole; Hauser, Joanna; Maier, Wolfgang; Kozel, Dejan; Henigsberg, Neven; Barreto, Mara Isabel; Placentino, Anna; Dernovšek, Mojca Zvezdana; Schulze, Thomas T.G.; Kalember, Petra; Zobel, Astrid; Czerski, Piotr M.; Larsen, Erik Roj; Souery, Daniel; Giovannini, C; Gray, Joanna; Lewis, Cathryn M.; Farmer, Anne; Aitchison, Katherine J.; McGuffin, Peter; Craig, Ian W.

doi:10.1038/tpj.2009.12

Cited by 194 publications

(157 citation statements)

References 38 publications

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“…This analysis confirmed that associated genetic markers were independent predictors of increase in suicidal ideation during treatment. Moreover, supporting this result, neither BDNF, NTRK2, nor ADRA2A genes were found to be predictors of overall response to antidepressants in the same sample (Uher et al, 2009a).…”

Section: Limitationsmentioning

confidence: 61%

Genetic Predictors of Increase in Suicidal Ideation During Antidepressant Treatment in the GENDEP Project

Perroud

Aitchison

Uher

et al. 2009

Neuropsychopharmacol

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102

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The aim of this study was to investigate genetic predictors of an increase in suicidal ideation during treatment with a selective serotonin reuptake inhibitor or a tricyclic antidepressant. A total of 796 adult patients with major depressive disorder who were treated with a flexible dosage of escitalopram or nortriptyline in Genome-based Therapeutic Drugs for Depression (GENDEP) were included in the sample and provided data on suicidal ideation. Nine candidate genes involved in neurotrophic, serotonergic, and noradrenergic pathways were selected based on previous association studies with suicidal ideation or behavior. Using a logistic regression model, 123 polymorphisms in these genes were compared between subjects with an increase in suicidal ideation and those without any increase in suicidal ideation. Polymorphisms in BDNF, the gene encoding the brain-derived neurotrophic factor, were significantly associated with an increase in suicidal ideation. The strongest association was observed for rs962369 in BDNF (p ¼ 0.0015). Moreover, a significant interaction was found between variants in BDNF and NTRK2, the gene encoding the BNDF receptor (p ¼ 0.0003). Among men taking nortriptyline, suicidality was also associated with rs11195419 SNP in the alpha 2A -adrenergic receptor gene (ADRA2A) (p ¼ 0.007). The associations observed with polymorphisms in BDNF suggest the involvement of the neurotrophic system in vulnerability to suicidality. Epistasis between BDNF and NTRK2 suggests that genetic variations in the two genes are involved in the same causal mechanisms leading to suicidality during antidepressant treatment. Among men, genetic variation in noradrenergic signaling may interact with norepinephrine reuptake-inhibiting antidepressants, thereby contributing to suicidality.

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Section: Limitationsmentioning

confidence: 61%

Genetic Predictors of Increase in Suicidal Ideation During Antidepressant Treatment in the GENDEP Project

Perroud

Aitchison

Uher

et al. 2009

Neuropsychopharmacol

Self Cite

102

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“…Subjects in the GENDEP study were recruited from nine European centers if they experienced at least one depressive episode of at least moderate severity (Uher et al, 2009). …”

Section: Discovery Cohort: Colaus|psycolausmentioning

confidence: 99%

Association of CRTC1 polymorphisms with obesity markers in subjects from the general population with lifetime depression

Quteineh¹,

Preisig²,

Rivera

et al. 2016

Journal of Affective Disorders

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Philippe Conus and Chin B. Eap, Association of CRTC1 polymorphisms with obesity markers in subjects from the general population with lifetime depression, Journal of Affective Disorders, http://dx.doi.org/10. 1016/j.jad.2016.03.031 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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“…Uher et al, 2009) were specific to predict treatment response. The substances used for treatment in our study were dual acting substances that modulate both serotonergic and noradrenergic systems in a different way.…”

Section: Volumementioning

confidence: 99%

Brain activation predicts treatment improvement in patients with major depressive disorder

Samson

Meisenzahl

Scheuerecker

et al. 2011

Journal of Psychiatric Research

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a b s t r a c tMajor depressive disorder (MDD) is associated with alterations in brain function that might be useful for therapy evaluation. The current study aimed to identify predictors for therapy improvement and to track functional brain changes during therapy. Twenty-one drug-free patients with MDD underwent functional MRI twice during performance of an emotional perception task: once before and once after 4 weeks of antidepressant treatment (mirtazapine or venlafaxine). Twelve healthy controls were investigated once with the same methods. A significant difference between groups was a relative greater activation of the right dorsolateral prefrontal cortex (dlPFC) in the patients vs. controls. Before treatment, patients responding better to pharmacological treatment showed greater activation in the dorsomedial PFC (dmPFC), posterior cingulate cortex (pCC) and superior frontal gyrus (SFG) when viewing of negative emotional pictures was compared with the resting condition. Activations in the caudate nucleus and insula contrasted for emotional compared to neutral stimuli were also associated with successful treatment. Responders had also significantly higher levels of activation, compared to non-responders, in a range of other brain regions. Brain activation related to treatment success might be related to altered self-referential processes and a differential response to external emotional stimuli, suggesting differences in the processing of emotionally salient stimuli between those who are likely to respond to pharmacological treatment and those who will not. The present investigation suggests the pCC, dmPFC, SFG, caudate nucleus and insula may have a key role as a biological marker for treatment response and predictor for therapeutic success.

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Genetic predictors of response to antidepressants in the GENDEP project

Cited by 194 publications

References 38 publications

Genetic Predictors of Increase in Suicidal Ideation During Antidepressant Treatment in the GENDEP Project

Genetic Predictors of Increase in Suicidal Ideation During Antidepressant Treatment in the GENDEP Project

Association of CRTC1 polymorphisms with obesity markers in subjects from the general population with lifetime depression

Brain activation predicts treatment improvement in patients with major depressive disorder

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