Interaction of 5-HTTLPR and a Variation on the Oxytocin Receptor Gene Influences Negative Emotionality

Background: Pharmacological studies indicate a functional interaction between the serotonergic and oxytocinergic system. Methods: This study tested for an interaction of the prominent serotonin transporter polymorphism (SLC6A4) and an oxytocin receptor gene variation on individual differences in negative emotionality in healthy Caucasians (n = 750). Results: Participants carrying both the homozygous LL-variant of the serotonin transporter polymorphism and the TT variant of the single nucleotide polymorphism rs2268498 on the oxytocin receptor gene showed lowest scores on the personality dimensions Fear and Sadness of the Affective Neuroscience Personality Scales, as well as on an underlying factor Negative Emotionality. Conclusions: The observed interaction effect provides converging evidence from human molecular genetics that serotonergic and oxytocinergic neurotransmission are entwined and play a crucial role for human personality with implications for affective disorders.