Article

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: 3.89). 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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    • "Our study also indicated that A:A haplotype (rs4853694:rs909270) was less frequent among BP with history of SB.. Therefore, our results would add some data to those studies concerning SNPs at the gene encoding INPP1 which have supported a role for genetic variability at the INPP1 gene in terms of lithium's effect on mood stability (Michelon et al., 2006; Steen et al., 1998), although one study failed to replicate this association (Piccardi et al., 2002). This molecular variability in both IMPA2 and INPP1 genes comports with studies reporting alterations in the phospoinositol pathway in suicides (Pacheco et al., 1996; Pandey and Dwivedi, 2010) Genetic variability at the gene encoding GSK3b may be a potential risk factor for attempting suicide in BD: T-allele carriers of the rs1732170 and A-allele carriers of the rs11921360-GSK3b gene had approximately two-fold and three-fold greater risk of being suicide attempters, respectively , compared to those homozygous for the alternative allele. We also found higher frequencies of C:A haplotype and lower frequencies of A:C haplotype (rs1732170:rs11921360) E. Jim enez et al. 1456 Author's personal copy Table 2 Genotype and allele frequencies of variations in the IMPA1, IMPA2, INPP1, GSK3a and GSK3b genes. "

    Full-text · Article · Oct 2013 · European Neuropsychopharmacology
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    • "Multiple lines of evidence indicate that BDNF is present at low levels in the blood cells and plasma of depressed patients. Postmortem suicide victims with or without depression and genetic association studies linking BDNF to suicide suggest that suicidal behavior may be associated with a decrease in BDNF function.37,38 BDNF alone or in combination with other neurotransmitters is known to regulate synaptic plasticity, neurogenesis, and neuronal survival through its specific signaling pathways.39,40 "
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    ABSTRACT: Despite the devastating effect of suicide on numerous lives, there is still a lack of knowledge concerning its neurochemical aspects. There is increasing evidence that brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are involved in the pathophysiology and treatment of depression through binding and activating their cognate receptors TrkB and TrkA respectively. The present study was performed to examine whether the expression profiles of BDNF and/or TrkB as well as NGF and/or TrkA were altered in the hippocampus of postmortem brain of the participants, who had committed suicide and whether these alterations were associated with specific psychopathologic conditions. These studies were performed on the hippocampus of 21 suicide victims and 19 non-psychiatric control individuals. The protein and mRNA levels of BDNF, TrkB, NGF, and TrkA were determined by sandwich enzyme-linked immunosorbent assay, Western blot and reverse transcription-PCR. Given the importance of BDNF and NGF and their cognate receptors in mediating physiological functions, including cell survival and synaptic plasticity, our findings of reduced expression of BDNF, TrkB, NGF, and TrkA on both the protein and mRNA levels of postmortem brains of suicide victims suggest that these molecules may play an important role in the pathophysiological aspects of suicidal behavior.
    Full-text · Article · Aug 2013 · Clinical Medicine Insights: Pathology
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    • "Our study also indicated that A:A haplotype (rs4853694:rs909270) was less frequent among BP with history of SB.. Therefore, our results would add some data to those studies concerning SNPs at the gene encoding INPP1 which have supported a role for genetic variability at the INPP1 gene in terms of lithium's effect on mood stability (Michelon et al., 2006; Steen et al., 1998), although one study failed to replicate this association (Piccardi et al., 2002). This molecular variability in both IMPA2 and INPP1 genes comports with studies reporting alterations in the phospoinositol pathway in suicides (Pacheco et al., 1996; Pandey and Dwivedi, 2010) Genetic variability at the gene encoding GSK3b may be a potential risk factor for attempting suicide in BD: T-allele carriers of the rs1732170 and A-allele carriers of the rs11921360-GSK3b gene had approximately two-fold and three-fold greater risk of being suicide attempters, respectively , compared to those homozygous for the alternative allele. We also found higher frequencies of C:A haplotype and lower frequencies of A:C haplotype (rs1732170:rs11921360) 5 Genetic variability at IMPA2, INPP1 and GSK3b increases the risk of suicidal behavior in bipolar patients "
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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.
    Full-text · Article · Feb 2013 · European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology
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