title: The impact of serotonin receptor 1A and 2A gene polymorphisms and interactions on suicide attempt and suicide risk in depressed patients with insufficient response to treatment--a European multicentre study.
abstract: So far, associations between serotonergic neurotransmission pathways and suicidality have been reported. The aim of our study was to investigate the role of genetic polymorphisms and gene-gene interactions of the 5-HTR1A and the 5-HTR2A gene on suicide risk and/or a personal history of suicide attempts. A total of 374 major depressive disorder patients, adequately treated with antidepressants for at least 4 weeks, were collected in the context of a European multicentre study on treatment-resistant depression. We assessed suicidality using the Mini International Neuropsychiatric Interview and the Hamilton Rating Scale for Depression (HAM-D). Treatment response was defined as HAM-D ≤ 17 and remission as HAM-D ≤ 7 after 4 weeks of adequate antidepressant treatment. The 5-HTR1A rs6295 (C-1019G) single nucleotide polymorphism (SNP) and the 5-HTR2A rs7997012, rs6313, rs643627 and rs17288723 SNPs were selected for genotyping. Using logistic regression analyses, no association (P<0.05) could be found between any SNP and neither suicide risk nor personal history of suicide attempts. Interactions between 5HTR1A rs6295 and 5HTR2A rs6313 in suicide risk, and 5HTR1A rs6295 and 5HTR2A rs643627 in a personal history of suicide attempts have been reported (P=0.027 and 0.036, respectively); however, the results did not survive multiple testing correction. In conclusion, our study shows no association between 5HTR1A or 5HTR2A gene polymorphisms and both current suicide risk and personal history of suicide attempts. In addition, epistatic effects of 5HTR1A and 5HTR2A genes on suicidal behaviour were not significant, although sample size limitations do not allow definitive conclusions.
authors.affiliation: aDepartment of Psychiatry and Psychotherapy, University Hospital of Psychiatry, University of Bern, Bern, Switzerland bDepartment of Psychiatry and Psychotherapy, Medical University of Vienna cZentrum für Seelische Gesundheit Leopoldau, BBRZ-Med, Vienna dZentrum für Seelische Gesundheit Muldenstrasse, BBRZ-Med, Linz, Austria eINSERM U1061, University of Montpellier, FondaMental Foundation, Montpellier, France fDepartment of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy gLaboratory of Experimental Neurology, National Fund of Scientific Research, Université Libre de Bruxelles hUniversité Libre de Bruxelles iLaboratoire de Psychologie Medicale, Université Libre de Bruxelles and Psy Pluriel, Centre Europe en de Psychologie Medicale, Bruxelles, Belgium jDepartment of Toxicology, Faculty of Pharmacy, University of Gazi, Etiler Ankara, Turkey kChaim Sheba Medical Center, Tel-Hashomer, Israel lImperial College, School of Medicine, University of London, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Höfer
authors.forename: Alexandra
authors.initials: A
authors.lastname: Schosser
authors.forename: Raffaella
authors.initials: R
authors.lastname: Calati
authors.forename: Alessandro
authors.initials: A
authors.lastname: Serretti
authors.forename: Isabelle
authors.initials: I
authors.lastname: Massat
authors.forename: Neslihan A
authors.initials: NA
authors.lastname: Kocabas
authors.forename: Anastasios
authors.initials: A
authors.lastname: Konstantinidis
authors.forename: Julien
authors.initials: J
authors.lastname: Mendlewicz
authors.forename: Daniel
authors.initials: D
authors.lastname: Souery
authors.forename: Joseph
authors.initials: J
authors.lastname: Zohar
authors.forename: Alzbeta
authors.initials: A
authors.lastname: Juven-Wetzler
authors.forename: Stuart
authors.initials: S
authors.lastname: Montgomery
authors.forename: Siegfried
authors.initials: S
authors.lastname: Kasper
mesh_terms: D000328:Adult; D061218:Depressive Disorder, Treatment-Resistant / Q000188:drug therapy* / Q000235:genetics* / Q000523:psychology; D005060:Europe; D005260:Female; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011569:Psychiatric Status Rating Scales; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics*; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics*; D012306:Risk; D013405:Suicide / Q000706:statistics & numerical data*; D013406:Suicide, Attempted / Q000706:statistics & numerical data*
chemical_list: D044402:Receptor, Serotonin, 5-HT2A; D044282:Receptor, Serotonin, 5-HT1A