The cortical surface area of the insula mediates the effect of DBH rs7040170 on novelty seeking

Novelty seeking (NS) is a personality trait important for adaptive functioning, but an excessive level of NS has been linked to psychiatric disorders such as ADHD and substance abuse. Previous research has investigated separately the neural and genetic bases of the NS trait, but results were mixed and neural and genetic bases have yet to be examined within the same study. In this study, we examined the interrelationships among the dopamine beta-hydroxylase (DBH) gene, brain structure, and the NS trait in 359 healthy Han Chinese subjects. We focused on the DBH gene because it encodes a key enzyme for dopamine metabolism, NS is believed to be related to the dopaminergic system and has been reported associated with DBH variation. Results showed a significant positive association between the cortical surface area of the left insula and NS score. Furthermore, the DBH genetic polymorphism at the SNP rs7040170 was strongly associated with both the surface area of the left insula and NS score, with G carriers having a larger left insula surface area and a higher NS score than AA homozygotes. Subsequent path analysis suggested that the insula partially mediated the association between the DBH gene and the NS trait. Our data provided the first evidence for the involvement of the insula in the dopamine-NS relationship. Future studies of molecular mechanisms underlying the NS personality trait and related psychiatric disorders should consider the mediation effect of the neural structure.