Variation of 5-HTTLPR and Deficits in Emotion Regulation: A Pathway to Risk?

Genetic variation in the serotonergic system within the brain has been a significant focus of psychiatric research over the last several decades. In particular, the serotonin transporter (5-HTT) gene (SLC6A4) has been tied to early emotion processing biases. However, a clear understanding of how genetic variation of SLC6A4 may influence clinically salient emotional phenomena is still elusive. In this investigation, we focused on examining variation in the 5-HTT-linked polymorphic region (5-HTTLPR; including the single nucleotide polymorphism rs25531 which alters genotype interpretation) and real-time emotion responses evoked in the laboratory using a paradigm designed to spontaneously induce emotion regulation. Across 2 studies we show that for healthy individuals with 2 copies of the functional short (S′) allele there is weakened down-regulation of negative emotion. In addition, we found greater electrodermal responses as well as both negative and positive emotion in association with the S′ allele in 1 of the 2 samples. These findings provide evidence that the S′ allele may promote system-wide heightened emotional reactivity in healthy subjects. Both phenomena, observed here in a healthy population, are strongly linked to the development of psychiatric disease. As such, these findings have implications for S′ carriers' vulnerability to affective disorders, as well as suggest potential targets for future clinical investigation.