P.2.b.023 A single dose of mirtazapine modulates neuronal responses to spoken emotional narratives in healthy volunteers

Abstract

serotonin transporter, three SNPs of the serotonin-1A receptor gene (HTR1A) and six SNPs of the galanin-1 receptor gene (GALR1) were genotyped [1,2]. Phenotypic outcome measures included lifetime depression and currant depression (Brief Symptoms Inventory with additional items). Stress-related environmental factors were measured by a short version of Childhood Trauma Questionnaire for childhood adversity, and the list of Threatening Experiences for recent negative life events. Statistical analysis was performed by PLINK v1.07. Age and sex were covariates in all analyses. We also applied a multivariate system-based Bayesian analysis of relevance for the GALR1 [2]. Results: In the total population, excluding life stressors from the model, none of the investigated polymorphisms showed relevance for depression-related phenotypes. In contrast, several significant effects in interaction with life stressors were found. Childhood adversity showed significant interactions with two SNPs of the GALR1. Significant interaction with recent life events were found with 5-HTTLPR, all HTR1A SNPs, and another SNP of the GALR1. Relevance calculations stratified for Childhood adversity and Recent Negative Life events confirmed that GALR1 is highly relevant in the interaction with childhood adversity, but the relevance for modulating the effect of recent negative life events is only mild. Furthermore, the relevance of this gene is present only in highly exposed persons. Conclusions: Our studies are in agreement with previous findings that major depression is a stress-associated disorder, and thus, single genetic effects without the inclusion of stress exposure in the model are difficult to identify. Furthermore, these data provide evidence that risk for depression after childhood maltreatment and recent negative life events involve also different genes and thus, at least partially separate neuronal pathways.