Variations in central serotonergic activity - relevance of the 5-HTTLPR, life events and their interaction

The 5-HTTLPR and its interaction with adverse life events has been studied widely; especially with regard to depression. Few studies are available relating the respective association with acute serotonergic functionality. We examined the effects of the 5-HTTLPR, life events and their interaction on serotonergic responsivity using S-citalopram (10mg) in a placebo-controlled double-blind neuroendocrine challenge paradigm (n=59 healthy males). We considered positive and negative life events, life events experienced during the last year and accumulated over the whole life span and possible mediating effects of neuroticism, extraversion and openness to experience. We demonstrated associations of life events experienced during the last year: negative life events were positively associated with cortisol-responses in the challenge paradigm (β=0.28, p<0.05), while positive life events were inversely associated (β=-0.29, p<0.05). Neither the main effect of 5-HTTLPR-genotype nor its interactions with life events predicted the acute serotonergic functionality. In addition, openness for feelings significantly predicted the serotonergic responsivity, while no other personality traits measured in this study mediated the effect of life events. Our results question not only the stability of serotonergic activity but, importantly, add to the literature concerning the serotonergic system as a general threshold modulating system, i.e. being associated with the processing of positive as well as negative stimuli.