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The Impact of BDNF Polymorphisms on Suicidality in Treatment-Resistant Major Depressive Disorder: A European
Alexandra Schosser1, Laura Carlberg1, Raffaella Calati1
1Department of Psychiatry and Psychotherapy, Medical University, Vienna, Austria; Zentrum für Seelische Gesundheit, Leopoldau, Austria; INSERM U1061, University of Montpellier, FondaMental Foundation, Montpellier, France; Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy; Laboratory of Experimental Neurology, National Fund of Scientific Research, Brussels, Belgium; Université Libre de Bruxelles, Brussels, Belgium; Laboratoire de Psychologie Medicale, Université Libre de Bruxelles and Psy Pluriel, Centre Europe en de Psychologie Medicale, Brussels, Belgium; Chaim Sheba Medical Center, Tel-Hashomer, Israel; Imperial College, School of Medicine, University of London, United Kingdom.
Background:
Numerous studies have reported associations between the brain-derived neurotrophic factor (BDNF) gene and psychiatric disorders, including suicidal behavior, although with conflicting results.
Methods:
A total of 250 major depressive disorder patients were collected in the context of a European multicenter resistant depression study and treated with antidepressants at adequate doses for at least 4 weeks. Suicidality was assessed using the Mini International Neuropsychiatric Interview and Hamilton Rating Scale for Depression, and treatment response using the HAM-D. Genotyping was performed for the functional Val66Met polymorphism (rs6265) and 7 additional tagging single nucleotide polymorphisms within the BDNF gene.
Results:
Neither BDNF single markers nor haplotypes were found to be associated with suicide risk and lifetime history of suicide attempts. Gender-specific analyses revealed nonsignificant single marker (rs908867) and haplotypic association with suicide risk in males after multiple testing correction. Analyzing treatment response phenotypes, the functional Val66Met polymorphism as well as rs10501087 showed significant genotypic and haplotypic association with suicide risk in remitters (n=34, 13.6%).
Conclusions:
Considering the sample size, the present findings need to be replicated in larger samples to confirm or refute a role of BDNF in the investigated suicidal behavior phenotypes.
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