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Many association studies have reported associations between the brain-derived neurotrophic factor (BDNF) gene and psychiatric disorders including major depression (MDD). The BDNF gene has further been associated with suicidal behaviour, as well as with treatment response, although with conflicting results. In the present study, we further elucidate the impact of BDNF in MDD patients with suicide risk and/or a personal history of suicide attempts. Two hundred fifty MDD patients were collected in the context of a European multicentre resistant depression study and treated with antidepressants at adequate doses for at least 4 weeks. Suicidality was assessed using Mini International Neuropsychiatric Interview (MINI) and 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 treatment with antidepressants at adequate dose. Genotyping was performed for eight SNPs within the BDNF gene. With regard to suicide risk and personal history of suicide attempts, neither single marker nor haplotypic association was found with any SNP after multiple testing correction. However, in gender-specific analyses, we found haplotypic association with suicide risk in males, but not in females (rs925946-rs10501087-rs6265, rs10501087-rs6265-rs122733). The only single-marker association with suicide risk in males (rs908867) did not resist multiple testing correction. No significant associations were found in gender-specific analyses with regard to a personal history of suicide attempts. In conclusion, we found two BDNF haplotypes significantly associated with suicide risk in male MDD patients. However, replication in larger well-defined cohorts is required to dissect this further. [ABSTRACT FROM AUTHOR]

Suicidal behaviour runs in families and the existence of genetic vulnerability to suicidality is well-established. Mental disorders, especially depression, are present in more of 90% of suicides. The incidence of treatment emergent suicidal ideation in major depression (MDD) varies from 4% to 20%, depending on the definition of suicidal ideation and sample characteristics. In the present study, we further elucidated the impact of depression candidate genes in treatment emergent suicidal ideation in MDD. One hundred-seventy MDD patients were collected in the context of a resistant depression study and treated with antidepressants at adequate doses for at least 4 weeks. MDD subjects were genotyped for SNPs within the COMT gene, BDNF, DTNBP1, 5HT1A, 5HT2A, GNB3, GRIK4, PTGS1, PTGS2, CREB, and cytochrome P450 CYP1A2, CYP2C9, CYP2C19 and CYP2D6 gene. Response, remission and treatment resistance, as well as suicidality information derived from Mini International Neuropsychiatric Interview (MINI) and Hamilton Rating Scale for Depression (HAM-D) were recorded. A quantitative and measure of suicidal behaviour was defined using the Hamilton rating scale (score 0 to 4) and the MINI-item (yes/no) on suicidality in a large cohort of depression cases. In addition, we tested for association with ‘serious suicidal attempts’ corresponding to a HAMD score of 4 (discrete trait analyses). Results of this candidate gene approach in treatment emergent suicidal ideation in MDD will be presented and discussed. [ABSTRACT FROM AUTHOR]