Exploring the Association between Serum BDNF and Attempted Suicide.
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ABSTRACT:
SUBMITTER: Eisen RB
PROVIDER: S-EPMC4848497 | biostudies-other | 2016 Apr
REPOSITORIES: biostudies-other
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Project description:BackgroundThere is growing evidence that serum lipid concentrations may be associated with attempted suicide in patients with major depressive disorder (MDD), but these findings remain controversial. Thus, we performed a comprehensive meta-analysis to quantitatively assess the associations between serum lipid concentrations and attempted suicide in MDD patients.Materials and methodsElectronic databases (PubMed, Embase, the Cochrane Library and the China National Knowledge Library) were searched for relevant literature up to 10 February 2020. We used a random-effects model based on heterogeneity amongst studies and generated pooled standardised mean differences (SMDs).ResultsThirty-two studies comprising 7,068 subjects met the inclusion criteria. A pooled analysis showed that compared with non-attempters, MDD patients who had attempted suicide had significantly lower serum concentrations of total cholesterol (TC) (SMD: -0.63, 95% CI: -0.83 to -0.44) and low-density lipoprotein cholesterol (LDL-C) (SMD: -0.69, 95% CI: -1.04 to -0.34), but the serum concentrations of high-density lipoprotein cholesterol (HDL-C) (SMD: -0.12, 95% CI: -0.33 to 0.10) and triglycerides (TGs) (SMD: 0.00, 95% CI: -0.20 to 0.20) were not significantly different between the two groups. Subgroup and meta-regression analysis indicated that heterogeneity with respect to TC concentrations may be due to different ages (p = 0.041) and sample sizes (p = 0.016) of studies, and that heterogeneity with respect to HDL-C concentrations may be partly due to different settings of studies (p = 0.017).ConclusionsThis meta-analysis demonstrated that lower concentrations of TC and LDL-C, but not of HDL-C and TGs, were associated with attempted suicide in MDD patients. This indicates that TC and LDL-C may be useful as biological markers for predicting whether MDD patients may attempt to commit suicide.
| S-EPMC7728216 | biostudies-literature
Project description:The heritable component to attempted and completed suicide is partly related to psychiatric disorders and also partly independent of them. Although attempted suicide linkage regions have been identified on 2p11-12 and 6q25-26, there are likely many more such loci, the discovery of which will require a much higher resolution approach, such as the genome-wide association study (GWAS). With this in mind, we conducted an attempted suicide GWAS that compared the single-nucleotide polymorphism (SNP) genotypes of 1201 bipolar (BP) subjects with a history of suicide attempts to the genotypes of 1497 BP subjects without a history of suicide attempts. In all, 2507 SNPs with evidence for association at P<0.001 were identified. These associated SNPs were subsequently tested for association in a large and independent BP sample set. None of these SNPs were significantly associated in the replication sample after correcting for multiple testing, but the combined analysis of the two sample sets produced an association signal on 2p25 (rs300774) at the threshold of genome-wide significance (P=5.07 × 10(-8)). The associated SNPs on 2p25 fall in a large linkage disequilibrium block containing the ACP1 (acid phosphatase 1) gene, a gene whose expression is significantly elevated in BP subjects who have completed suicide. Furthermore, the ACP1 protein is a tyrosine phosphatase that influences Wnt signaling, a pathway regulated by lithium, making ACP1 a functional candidate for involvement in the phenotype. Larger GWAS sample sets will be required to confirm the signal on 2p25 and to identify additional genetic risk factors increasing susceptibility for attempted suicide.
| S-EPMC4021719 | biostudies-literature
Project description:Epidemiological studies, such as family, twin, and adoption studies, demonstrate the presence of a heritable component to both attempted and completed suicide. Some of this heritability is accounted for by the presence of comorbid psychiatric disorders, but the evidence also indicates that a portion of this heritability is specific to suicidality. The serotonergic system has been studied extensively in this phenotype, but findings have been inconsistent, possibly due to the presence of multiple susceptibility variants and/or gene-gene interactions. In this study, we genotyped 174 tag and coding single nucleotide polymorphisms (SNPs) from 17 genes within the serotonin pathway on 516 subjects with a major mood disorder and a history of a suicide attempt (cases) and 515 healthy controls, with the goal of capturing the common genetic variation across each of these candidate genes. We tested the 174 markers in single-SNP, haplotype, gene-based, and epistasis analyses. While these association analyses identified multiple marginally significant SNPs, haplotypes, genes, and interactions, none of them survived correction for multiple testing. Additional studies, including assessment in larger sample sets and deep resequencing to identify rare causal variants, may be required to fully understand the role that the serotonin pathway plays in suicidal behavior.
| S-EPMC4021704 | biostudies-literature
Project description:We report the results of a high-density attempted suicide association study of the X chromosome, which genotyped 23,141 SNPs on 983 attempters and 1143 non-attempters and generated modest evidence for association for SH3KBP1 (P=1.07×10(-4)) and GRIA3 (P=4.01×10(-4)). These findings highlight the need for larger sample sets and meta-analytic approaches.
| S-EPMC4023562 | biostudies-literature
Project description:Family, twin, and adoption studies provide convincing evidence for a genetic contribution to suicidal behavior. The heritability for suicidal behavior depends in part on the transmission of psychiatric disorders, such as mood disorders and substance use disorders, but is also partly independent of them. Three linkage studies using the attempted suicide phenotype in pedigrees with bipolar disorder, major depression, or alcoholism have provided consistent evidence that 2p11-12 harbors a susceptibility gene for attempted suicide. A microarray expression study using postmortem brain samples has implicated a gene from the 2p11-12 candidate region, the trans-Golgi network protein 2 (TGOLN2) gene, as being consistently up-regulated in suicide cases as compared to controls. Here, we present a TGOLN2 case-control association study using nine single nucleotide polymorphisms (SNPs). These nine SNPs, which include seven tag SNPs and two coding SNPs, have been genotyped in 517 mood disorder subjects with a history of attempted suicide and 515 normal controls. Allelic and genotypic analyses of the case-control sample did not provide evidence for association with the attempted suicide phenotype. Eight of the nine SNPs provided supportive evidence for association (P-values ranging from 0.008 to 0.03) when we compared the attempted suicide cases with a history of alcoholism to the attempted suicide cases without a history of alcoholism. However, this association finding was not replicated in an independent sample. Taken together, these analyses do not provide support for the hypothesis that common genetic variation in TGOLN2 contributes significantly to the risk for attempted suicide in subjects with major mood disorders.
| S-EPMC3645851 | biostudies-literature
Project description:BackgroundThe term 'self-harm' encompasses both attempted suicide and non-suicidal self-injury (NSSI). Specific adolescent subpopulations such as ethnic or sexual minorities, and more controversially, those who identify as 'Alternative' (Goth, Emo) have been proposed as being more likely to self-harm, while other groups such as 'Jocks' are linked with protective coping behaviours (for example exercise). NSSI has autonomic (it reduces negative emotions) and social (it communicates distress or facilitates group 'bonding') functions. This study explores the links between such aspects of self-harm, primarily NSSI, and youth subculture.MethodsAn anonymous survey was carried out of 452 15 year old German school students. Measures included: identification with different youth cultures, i.e. Alternative (Goth, Emo, Punk), Nerd (academic) or Jock (athletic); social background, e.g. socioeconomic status; and experience of victimisation. Self-harm (suicide and NSSI) was assessed using Self-harm Behavior Questionnaire and the Functional Assessment of Self-Mutilation (FASM).ResultsAn "Alternative" identity was directly (r ≈ 0.3) and a "Jock" identity inversely (r ≈ -0.1) correlated with self-harm. "Alternative" teenagers self-injured more frequently (NSSI 45.5% vs. 18.8%), repeatedly self-injured, and were 4-8 times more likely to attempt suicide (even after adjusting for social background) than their non-Alternative peers. They were also more likely to self-injure for autonomic, communicative and social reasons than other adolescents.ConclusionsAbout half of 'Alternative' adolescents' self-injure, primarily to regulate emotions and communicate distress. However, a minority self-injure to reinforce their group identity, i.e. 'To feel more a part of a group'.
| S-EPMC4067739 | biostudies-literature
Project description:The polyamine system has been implicated in a number of psychiatric conditions, which display both alterations in polyamine levels and altered expression of genes related to polyamine metabolism. Studies have identified associations between genetic variants in spermidine/spermine N1-acetyltransferase (SAT1) and both anxiety and suicide, and several polymorphisms appear to play important roles in determining gene expression.We genotyped 63 polymorphisms, spread across four polyaminergic genes (SAT1, spermine synthase (SMS), spermine oxidase (SMOX), and ornithine aminotransferase like-1 (OATL1)), in 1255 French-Canadian individuals who have been followed longitudinally for 22 years. We assessed univariate associations with anxiety, mood disorders, and attempted suicide, as assessed during early adulthood. We also investigated the involvement of gene-environment interactions in terms of childhood abuse, and assessed internalizing and externalizing symptoms as endophenotypes mediating these interactions. Overall, each gene was associated with at least one main outcome: anxiety (SAT1, SMS), mood disorders (SAT1, SMOX), and suicide attempts (SAT1, OATL1). Several SAT1 polymorphisms displayed disease-specific risk alleles, and polymorphisms in this gene were involved in gene-gene interactions with SMS to confer risk for anxiety disorders, as well as gene-environment interactions between childhood physical abuse and mood disorders. Externalizing behaviors demonstrated significant mediation with regards to the association between OATL1 and attempted suicide, however there was no evidence that externalizing or internalizing behaviors were appropriate endophenotypes to explain the associations with mood or anxiety disorders. Finally, childhood sexual abuse did not demonstrate mediating influences on any of our outcomes.These results demonstrate that genetic variants in polyaminergic genes are associated with psychiatric conditions, each of which involves a set of separate and distinct risk alleles. As several of these polymorphisms are associated with gene expression, these findings may provide mechanisms to explain the alterations in polyamine metabolism which have been observed in psychiatric disorders.
| S-EPMC2994870 | biostudies-literature
Project description:Nicotine use is associated with the upregulation of brain-derived neurotrophic factor (BDNF) in serum. An association between smoking and the BDNF Val(66)Met polymorphism has also been found. The aim of this study is to examine the levels of serum BDNF in never-smokers, former smokers, and current smokers-with and without nicotine dependence-and to examine the interaction of the polymorphism and smoking status with serum BDNF.We used baseline serum and gene data of BDNF on 2,088 participants from the Netherlands Study of Depression and Anxiety (NESDA) to investigate smoking-BDNF association while controlling for potential confounding variables. Nicotine dependence was assessed with the Fagerstrom Test for Nicotine Dependence (FTND).Smokers with and without nicotine dependence had higher levels of serum BDNF than former and never-smokers. Nicotine dependence and number of cigarettes smoked per day did not add to the prediction of serum BDNF; however, total number of smoking years was a significant predictor of serum BDNF. There was no association of BDNF Val(66)Met, nor an interaction of this polymorphism and smoking status, with serum BDNF.Current smoking and higher number of smoking years are associated with higher levels of serum BDNF, and this is independent of the BDNF genotype. Nicotine dependence itself is not associated with a further increase or decrease of serum BDNF. Longitudinal investigations that address changes in serum BDNF in incident smokers and/or in quitters may be useful to understand the association of smoking with BDNF.
| S-EPMC4837993 | biostudies-literature
Project description:ObjectiveThe propensity of people vulnerable to suicide to make poor life decisions is increasingly well documented. Do they display an extreme degree of decision biases? The present study used a behavioral-decision approach to examine the susceptibility of low-lethality and high-lethality suicide attempters to common decision biases that may ultimately obscure alternative solutions and deterrents to suicide in a crisis.MethodWe assessed older and middle-aged (42-97 years) individuals who made high-lethality (medically serious) (n = 31) and low-lethality suicide attempts (n = 29). Comparison groups included suicide ideators (n = 30), nonsuicidal depressed participants (n = 53), and psychiatrically healthy participants (n = 28). Attempters, ideators, and nonsuicidal depressed participants had nonpsychotic major depression (DSM-IV criteria). Decision biases included sunk cost (inability to abort an action for which costs are irrecoverable), framing (responding to superficial features of how a problem is presented), underconfidence/overconfidence (appropriateness of confidence in knowledge), and inconsistent risk perception. Data were collected between June 2010 and February 2014.ResultsBoth high- and low-lethality attempters were more susceptible to framing effects as compared to the other groups included in this study (P ≤ .05, ηp2 = 0.06). In contrast, low-lethality attempters were more susceptible to sunk costs than both the comparison groups and high-lethality attempters (P ≤ .01, ηp2 = 0.09). These group differences remained after accounting for age, global cognitive performance, and impulsive traits. Premorbid IQ partially explained group differences in framing effects.ConclusionsSuicide attempters' failure to resist framing may reflect their inability to consider a decision from an objective standpoint in a crisis. Failure of low-lethality attempters to resist sunk cost may reflect their tendency to confuse past and future costs of their behavior, lowering their threshold for acting on suicidal thoughts.
| S-EPMC4697276 | biostudies-literature
Project description:BackgroundBrain-derived neurotrophic factor is implicated in the pathophysiology of major depressive disorder and suicide. Both are partly caused by early life adversity, which reduces brain-derived neurotrophic factor protein levels. This study examines the association of brain-derived neurotrophic factor Val66Met polymorphism and brain brain-derived neurotrophic factor levels with depression and suicide. We hypothesized that both major depressive disorder and early life adversity would be associated with the Met allele and lower brain brain-derived neurotrophic factor levels. Such an association would be consistent with low brain-derived neurotrophic factor mediating the effect of early life adversity on adulthood suicide and major depressive disorder.MethodsBrain-derived neurotrophic factor Val66Met polymorphism was genotyped in postmortem brains of 37 suicide decedents and 53 nonsuicides. Additionally, brain-derived neurotrophic factor protein levels were determined by Western blot in dorsolateral prefrontal cortex (Brodmann area 9), anterior cingulate cortex (Brodmann area 24), caudal brainstem, and rostral brainstem. The relationships between these measures and major depressive disorder, death by suicide, and reported early life adversity were examined.ResultsSubjects with the Met allele had an increased risk for depression. Depressed patients also have lower brain-derived neurotrophic factor levels in anterior cingulate cortex and caudal brainstem compared with nondepressed subjects. No effect of history of suicide death or early life adversity was observed with genotype, but lower brain-derived neurotrophic factor levels in the anterior cingulate cortex were found in subjects who had been exposed to early life adversity and/or died by suicide compared with nonsuicide decedents and no reported early life adversity.ConclusionsThis study provides further evidence implicating low brain brain-derived neurotrophic factor and the brain-derived neurotrophic factor Met allele in major depression risk. Future studies should seek to determine how altered brain-derived neurotrophic factor expression contributes to depression and suicide.
| S-EPMC6007393 | biostudies-literature