Firstly, our results are consistent with previous pathophysiological data obtained in various experimental models, including knockout mice, stress-reared rhesus macaques and human functional brain imaging32. The serotonin transporter genotype has been shown to be associated with differences in physiological responsiveness to stress conditions in these models, with a relative loss of serotonin transporter gene function being associated with greater vulnerability to environmental stress in all species tested3334. 5HTTLPR not only regulates serotonergic brain transmission, but carriers of the short allele also display various physiological abnormalities such as increased amygdala reactivity and fear conditioning, as well as alterations in hypothalamo-pituitary-adrenal axis reactivity33. Therefore, short allele carriers might present with a decreased ability to appropriately regulate stress responses, thereby lowering the threshold for the occurrence of a first BD episode.
