The identification of factors determining the variability of the AAO in BD is of crucial importance as an early AAO consistently associates with a more severe clinical profile and a poor prognosis124. The identification of risk factors for an earlier AAO could therefore guide both preventive and more personalized strategies in those at risk of developing BD. Both genetic and environmental determinants are thought relevant to AAO heterogeneity in BD1. In this study, we provided results suggesting an interaction between SLC6A4 promoter variants and emotional trauma on the AAO of BD. In the French sample AAO significantly decreased in the presence of trauma mainly in ‘SS’ carriers, this being significant after correction for multiple testing. Regression analyses suggested (although only nominally significant) that emotional traumatic events might be of special interest when studying environmental risk factors associated with an early occurrence of BD. In the replication sample, the results were partly replicated with some nominal signals in favor an interaction between SLC6A4 promoter variants and emotional trauma on the AAO.
