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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 on current suicidal ideation in the dominant model (Q=0.0344).  5-HTTLPR  did not interact with childhood adversities or total number of recent life events on any phenotypes related to current suicidal risk, however, a significant interaction effect between  5-HTTLPR  and current relationship problems emerged in the case of current suicidal ideation in the dominant model (Q=0.0218) and in the case of thoughts about death and dying in the dominant (Q=0.0094) and additive models (Q=0.0281).    Conclusion  While  5-HTTLPR  did not influence previous suicide attempts or interacted with childhood adversities, it did influence current suicidal ideation with, in addition, an interaction with recent relationship problems supporting the involvement of  5-HTTLPR  in suicide. Our findings that  5-HTTLPR  impacts only certain types of suicide risk-related behaviors and that it interacts with only distinct types of recent stressors provides a possible explanation for previous conflicting findings.

frontiers in psychiatry

“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