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Objectives: Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis leads to impaired stress response. FK506-binding protein 51 (FKBP5), which influences HPA axis activity via glucocorticoid receptors, is supposed to play an important role in the regulation of negative feedback and glucocorticoid resistance. Since ineffective stress response mechanisms are considered as a biological background of suicide behavior, we aimed to analyze a possible association between FKBP5 functional polymorphisms and completed suicide., Methods: The selected FKBP5 polymorphisms rs1360780 and rs3800373 were genotyped in a sample of 563 suicide victims and 475 controls., Results: A significant association between the high-induction rs3800373 C allele and completed suicide was detected (OR = 1.36, p = 0.007). In this polymorphism, genotype distribution supported a codominant model of inheritance. The analyzed SNPs were in strong linkage disequilibrium (D' = 0.916 and r2 = 0.826) with the rs1360780 (T)-rs3800373 (C) haplotype apparently responsible for the observed association (OR = 1.34, p = 0.010)., Conclusion: The results of the present study indicate that genetic alterations in FKBP5 may influence vulnerability to suicide., (© 2015 S. Karger AG, Basel.)

The A allele of rs9939609 in the FTO gene predisposes to increased body mass index (BMI) and obesity. Recently we showed an inverse association between the obesity related A allele of rs9939609 and alcohol dependence which was replicated by others. Since this finding raises a possibility that FTO may be associated with other psychiatric phenotypes, we aimed to examine association of rs9939609 with completed suicide. We genotyped rs9939609 in 912 suicide victims and 733 controls using TaqMan approach. We observed an inverse association between suicide and the rs9939609 A allele (OR = 0.80, P = 0.002, Pcor = 0.006) with genotype distribution suggesting a co-dominant effect. Given the link between alcoholism and suicide under influence of alcohol reported in Polish population, confounding by alcohol addiction was unlikely due to apparently similar effect size among cases who were under influence of ethanol at the time of death (OR = 0.76, P = 0.003, N = 361) and those who were not (OR = 0.80, P = 0.007, N = 469). The search for genotype-phenotype correlations did not show significant results. In conclusion, our study proves that there is an inverse association between rs9939609 polymorphism in FTO gene and completed suicide which is independent from association between FTO and alcohol addiction.

Background: rs6943555 in AUTS2 has been shown to modulate ethanol consumption. We hypothesized that rs6943555 might be associated with completed suicide., Methods: We genotyped rs6943555 in 625 completed suicides and 3861 controls using real-time TaqMan Allelic Discrimination Assay. All individuals were Polish Caucasians., Results: We detected an association between suicide and rs6943555 A allele (OR = 1.17, P = 0.018 for allelic comparison, OR = 1.24, P = 0.013 for dominant, and OR = 1.18, P = 0.020 for co-dominant model of inheritance). The association remained significant after adjusting for age and gender (co-dominant: P = 0.002 and dominant model: P = 0.001). After stratifying suicides according to blood ethanol concentration (BAC≤ 20 mg/dl and BAC > 20 mg/dl) the association remained significant only for cases who committed suicide under influence of alcohol (co-dominant: OR  =  1.37, P = 0.004 and dominant model: OR = 1.45, P = 0.006). To validate this finding we genotyped another cohort of 132 cases. We reproduced the association between rs6943555 A allele and suicide under influence of ethanol (allelic comparison: OR = 1.55, P = 0.023; co-dominant : OR = 1.54, P = 0.031; dominant model: OR = 1.84, P = 0.015). Analyzing pooled suicides with BAC >20 mg/dl (N = 300) we found the association of rs6943555 A allele not only vs. controls (allelic OR = 1.41, P = 0.00029) but also vs. cases with BAC ≤ 20 mg/dl (N = 449, allelic OR = 1.33, P = 0.019)., Conclusions: In our study rs6943555 A allele is associated with suicide committed after drinking ethanol shortly before death. The rs6943555 A allele may be linked to adverse emotional reaction to ethanol, which could explain the association with lower consumption in general population as well as the predisposition to suicide under influence of ethanol.

MTHFR C677T polymorphism (rs1801133) was associated with numerous psychiatric conditions but no prior study investigated whether it predisposes to completed suicide. We typed rs1801133 in 692 suicide victims and 3257 controls representative of a Polish adult population (the WOBASZ cohort). Although we had a power of 0.8 to detect (at alpha 0.05) an allelic OR=1.19, we did not find significant difference among suicides vs. controls in the prevalence of the MTHFR 677T allele (OR=1.02, p=0.759) or the TT genotype (OR=1.01, p=0.926). Since among controls we found an association between TT and depression defined by Beck Depression Inventory (BDI, OR=1.61, p=0.049) we also compared suicides with controls without signs of depression (BDI ≤ 11) but found no association (OR=1.0, p=0.976). Analyses within suicides showed trends (not significant after Bonferroni correction) for correlations between the dose of the T allele and age at death among males and blood ethanol concentration among females, who committed suicide under the influence of alcohol. We conclude that MTHFR C677T polymorphism is not a risk factor for completed suicide. The sex-specific trends for correlations between rs1801133 and age at death, and blood ethanol concentration should be studied further., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: We hypothesized that DNA variants affecting neurodevelopment such as rs4307059 (CDH10/CDH9), rs930752 (NRXN1), rs6265 (BDNF) or rs10868235 (NTRK2) may predispose to completed suicide., Methodology: We used a case-control two-stage approach based on a discovery cohort (557 cases and ∼550 controls) and replication cohort (159 cases and 186 controls). The suicides were ascertained as consecutive cases autopsied at the Department of Forensic Medicine, Medical University of Warsaw, Poland., Results: In the discovery cohort we found an association between suicide and the CC genotype in the rs4307059 polymorphism (OR 1.64, p = 0.012). The trend for an overrepresentation of the CC homozygotes among suicides was replicated in the second cohort (OR 1.97, p = 0.056). Analysis in the pooled cohorts showed that rs4307059 CC was associated with completed suicide (OR 1.71, p = 0.002) also after Bonferroni correction (p(cor.) = 0.024). In an exploratory search for genotype-phenotype correlation we found that males with the rs4307059 CC genotype committed suicide earlier than those with CT/TT genotypes (p = 0.049)., Conclusions: The CC genotype of rs4307059 located in the region between CDH9 and CDH10 is associated with completed suicide in a Polish cohort., (Copyright © 2012 S. Karger AG, Basel.)

The association between suicide and a single nucleotide polymorphism (rs1386483) was examined in the recently identified tryptophan hydroxylase 2 (TPH2) gene. Blood samples of 143 suicide victims and 162 age- and sex-matched controls were examined. The frequency of the TT genotype in the TPH2 polymorphism was higher in suicide victims than in controls (17.5% vs. 8.6%; p = 0.02), particularly in those with a history of repeated suicide attempts (53.3% vs. 8.6%; p < 0.0001). The examined TPH2 polymorphism was found to be associated with suicide. This genetic marker may be particularly important in understanding risk of multiple suicide attempts. Further analyses are needed to confirm these results.

Aims: Despite the large number of suicides that occur with intoxication, little is known about the unique predictors of suicide after alcohol consumption. The goal of this study was to examine clinical and genetic risk factors for alcohol-related suicide., Methods: Data on 162 suicide victims were obtained from post-mortem examinations, police and prosecution inquiries, autopsy protocols and available medical records. Four single nucleotide polymorphisms in the central serotonin system and the renin-angiotensin system related genes previously found to be associated with suicide, alcohol dependence or depression were genotyped., Results: The strongest predictor of suicide under the influence of alcohol was alcohol dependence (OR = 4.63). Those who did not drink alcohol before suicide were more likely to have a diagnosis of major depressive disorder in their medical record and more often had the TT genotype of the tryptophan hydroxylase 2 gene., Conclusions: Suicide under the influence of alcohol is strongly connected with alcohol dependence. The TPH2 gene may play an important role in suicide vulnerability especially in individuals who did not drink alcohol before suicide.

Objective: Links between sleep problems and suicidality have been frequently described in clinical samples; however, this issue has not been well-studied in the general population. Using data from a nationally representative survey, we examined the association between self-reported sleep difficulties and suicidality in the United States., Methods: The WHO Composite International Diagnostic Interview was used to assess sleep problems and suicidality in the National Comorbidity Survey Replication (NCS-R). Relationships between three measures of sleep (difficulty initiating sleep, maintaining sleep, early morning awaking), and suicidal thoughts, plans, and attempts were assessed in logistic regression analyses, while controlling for demographic characteristics, 12-month diagnoses of mood, anxiety and substance use disorders, and chronic health conditions., Results: In multivariate models, the presence of any of these sleep problems was significantly related to each measure of suicidality, including suicidal ideation (OR=2.1), planning (OR=2.6), and suicide attempt (OR=2.5). Early morning awakening was associated with suicidal ideation (OR=2.0), suicide planning (OR=2.1), and suicide attempt (OR=2.7). Difficulty initiating sleep was a significant predictor of suicidal ideation and planning (ORs: 1.9 for ideation; 2.2 for planning), while difficulty maintaining sleep during the night was a significant predictor of suicidal ideation and suicide attempts (ORs: 2.0 for ideation; 3.0 for attempt)., Conclusions: Among community residents, chronic sleep problems are consistently associated with greater risk for suicidality. Efforts to develop comprehensive models of suicidality should consider sleep problems as potentially independent indicators of risk.

Objective: The present study was designed to examine the relationship between prior partner and non-partner aggression and suicidal ideation in patients seeking drug and alcohol treatment., Method: Patients entering drug and alcohol treatment (n=488) were screened for prior partner and non-partner aggression as well as recent suicidal thoughts. We examined the association between aggression and suicidal ideation in bivariate and multivariate models., Results: Within the past two weeks, 33% (159/488) of the sample reported suicidal ideation. In bivariate analyses, neither psychological nor physical aggression towards a non-partner was related to suicidal ideation. Partner psychological aggression was related to suicidal ideation in bivariate but not multivariate analyses. Physical aggression towards a partner was consistently related to higher rates of suicidal ideation even after controlling for other known risk factors (OR=1.8; CI=1.1-2.7). Mediational analyses indicate that this relationship was no longer significant after accounting for current negative affect., Conclusion: Suicidal ideation is common in patients seeking drug and alcohol treatment and particularly likely in those who report prior aggression towards a partner.

Background/aims: An association between the II genotype of the angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism and suicide was found among Japanese men. Our purpose was to replicate this finding in Caucasians and explore other putative genotypic associations among suicides., Methods: The ACE genotypes were studied by a 2-stage PCR method in 150 completed suicides and 165 age- and sex-matched controls., Results: We found an increase in the frequency of the ACEI allele among male victims of suicide compared to male controls (odds ratio, OR = 1.69, p < 0.006), female suicides (OR = 2.01, p = 0.006) and pooled controls (OR = 1.77, p = 0.001). Analysis of genotype distribution showed that the codominant model had the best fit (p = 0.7) whereas the recessive model could be rejected (p = 0.04). Among males we found an association between the number of the ACE I allele and the method of suicide: OR = 17.98, p(corrected) = 0.00003, for jumping from a height; OR = 0.36, p(corrected) = 0.048, for hanging. We also observed a trend for a negative effect of the number of copies of the ACE I allele on prevalence of depression (OR = 0.36, p = 0.013) and a trend for an effect on age at death (p = 0.021)., Conclusions: Our results suggest that low ACE activity associated with the I allele is a risk factor for suicide, especially in a subset of males. This may be of concern given the widespread use of drugs lowering ACE activity., (Copyright 2009 S. Karger AG, Basel.)