Oxytocin-Receptor Gene Modulates Reward-Network Connection and Relationship with Empathy Performance

Dandan Li,1– 3,* Long Zhang,4,* Tongjian Bai,4,* Bensheng Qiu,5 Chunyan Zhu,1– 3 Kai Wang1,2,4,6,7 1School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, People’s Republic of China; 2Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, People’s Republic of China; 3Research Center for Translational Medicine, Second Hospital of Anhui Medical University, Hefei, People’s Republic of China; 4Department of Neurology, First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 5Hefei National Laboratory for Physical Sciences at the Microscale and the Centers for Biomedical Engineering, University of Science and Technology of China., Hefei, People’s Republic of China; 6Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders, Hefei, People’s Republic of China; 7Collaborative Innovation Center of Neuropsychiatric Disorders and Mental Health, Hefei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chunyan Zhu; Kai Wang, Email ayswallow@126.com; wangkai1964@126.comIntroduction: Empathy traits are highly heritable and linked with reward processing. It is implicated that common variations of the oxytocin-receptor gene (OXTR) play a modulatory effect on empathic performance. However, it is unclear about the neural substrates underlying the modulatory effect of the OXTR genotype on empathic performance. This study aimed to characterize the modulatory effect of common OXTR variations on reward-circuitry function and its relationship with empathy.Methods: Based on the seed of the nucleus accumbens (NAcc; a key hub of reward circuitry), we examined differences in spontaneous local activity and functional connectivity between OXTR rs2268493 genotype groups and their relationship with empathic performance among 402 high-homogeneity participants.Results: Comparing with C carriers (CC/CT) group, the individuals with the rs2268493 TT genotype exhibited lower functional connectivity of the right NAcc with the medial prefrontal cortex (mPFC) and inferior frontal gyrus. Similarly lower functional connectivity was found between the left NAcc and mPFC. Consequently, no significant difference was found in the spontaneous local activity of NAcc.Discussion: Our findings suggested that common OXTR variations have a modulatory effect on the connection of the NAcc with the hub of empathic networks (mPFC and IFG), which may provide insight on the neural substrate underlying the modulatory effect of OXTR on empathic behavior.Keywords: empathy, oxytocin-receptor gene, reward network, RS-fMRI, rs2268493