Association of Unc-51-like Kinase 4 () with the reactivity of the extended reward system in response to conditioned stimuli.

Objectives: is an established candidate gene for mental disorders and antipsychotic treatment response. We investigated the association of functional genetic variation at the locus with the human extended dopaminergic reward system using fMRI during the performance of a well-established reward paradigm.

Methods: Two hundred and thirty-four patients were included in this study. Association of genetic variation in the gene with reward system functioning were determined using the Desire-Reason-Dilemma (DRD) paradigm which allows to assess brain activation in response to conditioned reward stimuli.

Results: Variant prioritisation revealed the strongest functional signatures for the variant rs17215589, coding for amino acid exchange Ala715Thr. For rs17215589 minor allele carriers, we detected increased activation responses to conditioned reward stimuli in the ventral tegmental area, nucleus accumbens and several cortical brain regions of the extended reward system.

Conclusions: Our findings provide further evidence in humans that genetic variation in may increase the vulnerability to mental disorders, by modulating the extended reward system function. Future studies are needed to confirm the modulation of the extended reward system by and to specify the role of this mechanism in the pathogenesis of psychiatric disorders.