“Out, out, brief candle! Life’s but a walking shadow”: 5-HTTLPR Is Associated With Current Suicidal Ideation but Not With Previous Suicide Attempts and Interacts With Recent Relationship Problems

Abstract

Background: Suicide is an unresolved psychiatric and public health emergency, claiming 800,000 lives each year, however, its neurobiological etiology is still not understood. In spite of original reports concerning the involvement of 5-HTTLPR in interaction with recent stress in the appearance of suicidal ideation and attempts, replication studies have yielded contradictory results. In our study, we analyzed the association between 5-HTTLPR and lifetime suicide attempts, current suicidal ideation, hopelessness and thoughts of death as main effects, and in interaction with childhood adversities, recent stress, and different types of recent life events in a general population sample. Methods: Two thousand and three hundred fifty-eight unrelated European volunteers were genotyped for 5-HTTLPR, provided phenotypic data on previous suicide attempts, and current suicidal ideation, hopelessness and thoughts about death, and information on childhood adversities and recent life events. Logistic and linear regression models were run with age, gender, and population as covariates to test for the effect of 5-HTTLPR as a main effect and in interaction with childhood adversities and recent life events on previous suicide attempts and current suicidal ideation. Benjamini-Hochberg FDR Q values were calculated to correct for multiple testing. Results: 5-HTTLPR had no significant effect on lifetime suicide attempts either as a main effect on in interaction with childhood adversities. 5-HTTLPR had a significant main effect

Inflamed Mind: Multiple Genetic Variants of IL6 Influence Suicide Risk Phenotypes in Interaction With Early and Recent Adversities in a Linkage Disequilibrium-Based Clumping Analysis

“…We could not identify clumps of variants interacting with recent stress on other suicide risk markers such as current thoughts of death or hopelessness. However, as specific genes and variants may mediate the effects of only specific types of stressors (53)(54)(55)65), we also looked at the interaction between IL6 variation and distinct recent stress types. Our models identified separate variant clumps significantly interacting with recent financial problems or personal problems on suicidal ideation, and with intimate relationship problems and social network problems on current thoughts of death, which once again suggests that different types of stressors may exert their effect via the mediation of different genetic variants.…”

Testing the role of inflammation in the relation of childhood maltreatment and suicidal ideation among young adults

“…While CM may explain later risk of suicidal ideation to an extent, mechanisms within this pathway are not entirely understood. Several biological and genetic systems have been investigated as risk mechanisms for suicidal ideation in the context of CM (Anda et al, 2010; Baumeister et al, 2016; Bokor et al, 2020; Brown & Hariri, 2006; Brundin et al, 2015). Specifically, CM has been shown to lead to hypersecretion of glucocorticoids that can desensitize inhibition of and indirectly activate the brain's stress response system (Brundin et al, 2015; Coelho et al, 2014; Fagundes et al, 2011).…”