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

Autor: Ana Petrovic, Daniel Souery, Cathryn M. Lewis, Rebecca G. Smith, Wolfgang Maier, Andrej Marusic, Rudolf Uher, Cristian Bonvicini, Petra Kalember, Lisbeth Jorgensen, Joanna Gray, Katherine J. Aitchison, Nader Perroud, Joanna Hauser, Thomas G. Schulze, Bhanu Gupta, Marcella Rietschel, Neven Henigsberg, Ian W. Craig, Anna Placentino, Anne Farmer, Ole Mors, Pawel Kapelski, Peter McGuffin, Astrid Zobel, P Huezo-Diaz
Rok vydání: 2009
Předmět:
Adult
Male
Oncology
medicine.medical_specialty
Candidate gene
medicine.drug_class
Serotonin reuptake inhibitor
Tricyclic antidepressant
Nortriptyline
Citalopram
Polymorphism
Single Nucleotide
Linkage Disequilibrium
03 medical and health sciences
Sex Factors
0302 clinical medicine
Receptors
Adrenergic
alpha-2
Internal medicine
medicine
Humans
Receptor
trkB
Escitalopram
Genetic Predisposition to Disease
Suicidal ideation
Pharmacology
Depressive Disorder
Major
Polymorphism
Genetic
Brain-Derived Neurotrophic Factor
medicine.disease
Antidepressive Agents
3. Good health
030227 psychiatry
Suicide
Psychiatry and Mental health
Logistic Models
Haplotypes
Major depressive disorder
Antidepressant
Female
medicine.symptom
Psychology
030217 neurology & neurosurgery
Follow-Up Studies
medicine.drug
Clinical psychology
Zdroj: Perroud, N, Aitchison, K J, Uher, R, Smith, R, Huezo-Diaz, P, Marusic, A, Maier, W, Mors, O, Placentino, A, Henigsberg, N, Rietschel, M, Hauser, J, Souery, D, Kapelski, P, Bonvicini, C, Zobel, A, Jorgensen, L, Petrovic, A, Kalember, P, Schulze, T G, Gupta, B, Gray, J, Lewis, C M, Farmer, A E, McGuffin, P & Craig, I 2009, ' Genetic predictors of increase in suicidal ideation during antidepressant treatment in the GENDEP project ', Neuropsychopharmacology, vol. 34, no. 12, pp. 2517-28 . https://doi.org/10.1038/npp.2009.81
ISSN: 1740-634X
0893-133X
DOI: 10.1038/npp.2009.81
Popis: Udgivelsesdato: 2009-Nov 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=0.0015). Moreover, a significant interaction was found between variants in BDNF and NTRK2, the gene encoding the BNDF receptor (p=0.0003). Among men taking nortriptyline, suicidality was also associated with rs11195419 SNP in the alpha(2A)-adrenergic receptor gene (ADRA2A) (p=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.
Databáze: OpenAIRE
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