DNA Methylation of Genes Involved in the HPA Axis in Presence of Suicide Behavior: A Systematic Review.

DNA methylation in genes of the hypothalamic-pituitary-adrenal (HPA) axis has been associated with suicide behavior. Through a systematic review, we aimed to evaluate DNA methylation levels of the genes involved in the HPA pathway and their association with suicide behavior. A search of articles was performed using PubMed and Science Direct, EBSCO. The terms included were "DNA methylation", "suicide", "epigenetics", "HPA axis" and "suicide behavior". This systematic review was performed by the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement. Six studies comprising 743 cases and 761 controls were included in this systematic review. The studies included individuals with suicide ideation, suicide attempts or completed suicide and childhood trauma, post-traumatic stress disorder (PTSD), or depression. One study reported hypermethylation in GR in childhood trauma, while two studies found hypermethylation of NR3C1 in childhood trauma and major depressive disorder (MDD). Only one study reported hypermethylation in BNDF in people with MDD. FKBP5 was found to be hypermethylated in people with MDD. Another study reported hypermethylation in CRHBP. SKA2 was reported to be hypermethylated in one study and another study found hypomethylated both in populations with PTSD. CRHR1 was found to be hypermethylated in people with MDD, and the last study found hypomethylation in CRH. Our result showed that patients with suicidal behavior showed a DNA methylation state of genes of the HPA axis in association with psychiatric comorbidity and with adverse events. Genes of the HPA axis could play a role in suicidal behavior associated with adverse events and pathologies. As a result, DNA methylation levels, proteins, and genes involved in the HPA axis could be considered for the search for biomarkers for the prevention of suicidal behavior in future studies.

High Serum Levels of IL-6 Are Associated with Suicide Attempt but Not with High Lethality Suicide Attempts: A Preliminary Case-Control Study.

Suicide attempts are an emerging health problem around the world. Increased levels of IL-6 have been associated with suicidal behavior. Therefore, the aims of this study were to evaluate the serum levels of IL-6 in individuals with suicide attempts and a comparison group and to associate the IL-6 levels with the lethality of the suicide attempt. Additionally, we associated the rs2228145 polymorphism of the IL6R gene with suicide attempts or with the IL-6 serum levels. Suicide attempts and their lethality were evaluated using the Columbia Suicide Severity Rating Scale. The serum concentrations of IL-6 were measured by the ELISA technique in individuals with suicide attempts and then compared to a control group. The rs2228145 polymorphism of the IL6R gene was analyzed by real-time polymerase chain reaction. We found elevated serum levels of IL-6 in the suicide attempt group when compared to the control group (F = 10.37, p = 0.002). However, we found no differences of the IL-6 levels between high and low lethality. The IL6R gene polymorphism rs2479409 was not associated with suicide attempts. Our data suggest that IL-6 serum is increased in individuals with suicide attempts.

Cannabis smoking increases the risk of suicide ideation and suicide attempt in young individuals of 11-21 years: A systematic review and meta-analysis.

BACKGROUND: Cannabis is the most frequently consumed drug around the world. Its use has been associated with increased suicide behaviors; nonetheless, the association of cannabis smoking and suicide behaviors in adolescents has not yet been established. The aim of this systematic review and meta-analysis was to evaluate the risk of suicide attempt, suicidal ideation or suicide planning in individuals of 11-21 years of age who smoke cannabis. METHODS: We performed an online searched using PubMed, EBSCO and Science Direct databases, up to July 2021. We calculated odds ratio with 95% confidence intervals to evaluate the association between suicide attempt, suicidal ideation or suicide planning and cannabis smoking in individuals of 11-21 years of age. RESULTS: Twenty studies reported suicide attempts in 34,859 young individuals, suicidal ideation in 26, 937 individuals, and suicide planning in 9054 young individuals. We found an increased risk of suicide attempt in cannabis smokers than in non-cannabis users (OR: 2.33; 95% CI: 1.78-3.05; Z p value; <0.0001; I2 = 97.12%), as well as a significant association between cannabis smoking and suicidal ideation (OR: 2.04; 95%CI: 1.64-2.53; Z p value: <0.001; I2: 94.88) and suicide planning (OR: 1.674; 95% CI: 1.554-1.804; Z p value: 0.000; I2: 92.609). Subgroup analyses showed that American teens have an increased risk of suicidal ideation; the meta-regression analysis revealed that age was negatively associated with the risk of suicide attempt. CONCLUSIONS: This meta-analysis shows that cannabis smoking increased the risk of suicide attempt, suicidal ideation and suicide planning in young individuals of 11-21 years of age. The high risk of suicide behaviors could vary depending on the population studied; therefore, more studies are necessary to corroborate the risk of presenting suicide behaviors in individuals of 11-21 years of age who smoke cannabis.

Increased Levels of Cortisol in Individuals With Suicide Attempt and Its Relation With the Number of Suicide Attempts and Depression.

Background: Abnormalities in the hypothalamic-pituitary-adrenal axis (HPA) have been reported in individuals with suicide behavior. The aim of the study was to evaluate cortisol levels in peripheral plasma of individuals with more than one suicide attempt. Methods: Cortisol concentrations in peripheral plasma were measured using the ELISA technique. Suicide attempts were evaluated by the Columbia Suicide Severity Rating Scale, while depression was evaluated by the Hamilton Depression Rating Scale. Results: We found elevated cortisol levels in the suicide attempt group when compared with healthy controls (F = 7.26, p-value = 0.008), but no statistical differences with the psychiatric diseases group (F = 1.49, p-value = 0.22). Cortisol levels were higher in individuals with depression (F = 8.99, P = 0.004) and in individuals with two or more suicide attempts (F = 13.56, P < 0.001). Conclusions: Cortisol levels are increased in individuals who attempt suicide and higher of cortisol concentrations in plasma regard to depression and more attempts of suicide.