Brain-derived neurotrophic factor and suicide pathogenesis.

Psychiatric Institute, Department of Psychiatry, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
Annals of Medicine (Impact Factor: 4.73). 03/2010; 42(2):87-96. DOI: 10.3109/07853890903485730
Source: PubMed

ABSTRACT Abstract Suicide is a major public health concern. The etiology and pathogenic mechanisms associated with suicidal behavior are poorly understood. Recent research on the biological perspective of suicide has gained momentum and appears to provide a promising approach for identifying potential risk factors associated with this disorder. One of the areas that have gained the most attention in suicide research is the role of brain-derived neurotrophic factor (BDNF), which participates in many physiological functions in the brain, including synaptic and structural plasticity. Several studies consistently show that expression of BDNF is reduced in blood cells of suicidal patients and in brains of subjects who committed suicide. Recent studies also demonstrate abnormalities in the functioning of BDNF, because its cognate receptors (tropomycin receptor kinase B and pan75 neurotrophin receptor) are abnormally active and/or expressed in the post-mortem brains of suicide subjects. There is further evidence of the role of BDNF in suicide as numerous studies show a strong association of suicidal behavior with BDNF functional polymorphism. Overall, it appears that abnormalities in BDNF signaling may serve as an important biological risk factor in the etiology and pathogenesis of suicide.

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    ABSTRACT: Bipolar patients (BP) are at high risk of suicide. Causal factors underlying suicidal behavior are still unclear. However, it has been shown that lithium has antisuicidal properties. Genes involved in its putative mechanism of action such as the phosphoinositol and the Wnt/β-catenine pathways could be considered candidates for suicidal behavior (SB). Our aim was to investigate the association of the IMPA1 and 2, INPP1, GSK3α and β genes with suicidal behavior in BP. 199 BP were recruited. Polymorphisms at the IMPA1 (rs915, rs1058401 and rs2268432) and IMPA2 (rs66938, rs1020294, rs1250171 and rs630110), INPP1 (rs3791809, rs4853694 and 909270), GSK3α (rs3745233) and GSK3β (rs334558, rs1732170 and rs11921360) genes were genotyped. All patients were grouped and compared according to the presence or not of history of SB (defined as the presence of at least one previous suicidal attempt). Single SNP analyses showed that suicide attempters had higher frequencies of AA genotype of the rs669838-IMPA2 and GG genotype of the rs4853694-INPP1gene compared to non-attempters. Results also revealed that T-allele carriers of the rs1732170-GSK3β gene and A-allele carriers of the rs11921360-GSK3β gene had a higher risk for attempting suicide. Haplotype analysis showed that attempters had lower frequencies of A:A haplotype (rs4853694:rs909270) at the INPP1 gene. Higher frequencies of the C:A haplotype and lower frequencies of the A:C haplotype at the GSK-3β gene (rs1732170:rs11921360) were also found to be associated to SB in BP. Therefore, our results suggest that genetic variability at IMPA2, INPP1 and GSK3β genes is associated with the emergence of SB in BP.
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