Genetic polymorphisms in the 5-HT and endocannabinoid systems moderate the association between childhood trauma and burnout in the general occupational population

Background: Interactions between the serotonin (5 -HT) and endocannabinoid (eCB) systems have been reported in the psychopathology of stress -related symptoms, while their interplay in regulating the relationship between childhood trauma and burnout remains unclear. In this study, we investigated the interaction of childhood trauma with genetic polymorphisms in these two systems in predicting burnout. Methods: Burnout, childhood trauma, and job stress were assessed using rating scales in 992 general occupational individuals. Genetic polymorphisms including HTR2A rs6313, 5-HTT rs6354 and FAAH rs324420, were genotyped. Linear hierarchical regression analysis and PROCESS macro in SPSS were used to examine two- and threeway interactions. Results: There were significant interactions of job stress x HTR2A rs6313 and childhood abuse x FAAH rs324420 on reduced personal accomplishment. Moreover, we found significant three-way interactions of childhood abuse x FAAH rs324420 x HTR2A rs6313 on cynicism and reduced personal accomplishment, childhood abuse x FAAH rs324420 x 5-HTT rs6354 on emotional exhaustion, and childhood neglect x FAAH rs324420 x 5-HTT rs6354 on reduced personal accomplishment. These results suggest that the FAAH rs324420 A allele carriers, when with some specific genetic polymorphisms of 5 -HT system, would show more positive associations between childhood trauma and burnout. Conclusions: Genetic polymorphisms in the 5 -HT and eCB systems may jointly moderate the impact of childhood trauma on burnout.