Format

Send to

Choose Destination
Sci Rep. 2018 Mar 29;8(1):5372. doi: 10.1038/s41598-018-23191-y.

Multilocus genetic profile in dopaminergic pathway modulates the striatum and working memory.

Wang C1,2, Liu B3,4, Zhang X3,4, Cui Y3,4, Yu C5, Jiang T6,7,8,9,10.

Author information

1
Shenzhen Key Laboratory of Affective and Social Cognitive Science, College of Psychology and Sociology, Shenzhen University, Shenzhen, 518060, China.
2
Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, 610054, P. R. China.
3
Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, China.
4
National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, China.
5
Department of Radiology, Tianjin Medical University General Hospital, Tianjin, China. chunshuiyu@vip.163.com.
6
Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, 610054, P. R. China. jiangtz@nlpr.ia.ac.cn.
7
Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, China. jiangtz@nlpr.ia.ac.cn.
8
National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, China. jiangtz@nlpr.ia.ac.cn.
9
CAS Center for Excellence in Brain Science, Institute of Automation, Chinese Academy of Sciences, Beijing, China. jiangtz@nlpr.ia.ac.cn.
10
The Queensland Brain Institute, University of Queensland, Brisbane, Australia. jiangtz@nlpr.ia.ac.cn.

Abstract

Dopamine is critical in pathophysiology and therapy of schizophrenia. Many studies have reported altered dopaminergic activity in the dorsal but not ventral striatum in schizophrenia. Based on the largest genome-wide association study of schizophrenia to date, we calculated the polygenic risk score (PGRS) of each subject in a healthy general group, including all variations in the set of functionally related genes involved in dopamine neurotransmitter system. We aimed to test whether the genetic variations in the dopaminergic pathway that have been identified as associated with schizophrenia are related to the function of the striatum and to working memory. We found that a higher PGRS was significantly associated with impairment in working memory. Moreover, resting-state functional connectivity analysis revealed that as the polygenic risk score increased, the connections between left putamen and caudate and the default mode network grew stronger, while the connections with the fronto-parietal network grew weaker. Our findings may shed light on the biological mechanism underlying the "dopamine hypothesis" of schizophrenia and provide some implications regarding the polygenic effects on the dopaminergic activity in the risk for schizophrenia.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center