文章基本信息

标题：Multilocus genetic profile in dopaminergic pathway modulates the striatum and working memory
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作者：Chao Wang ; Bing Liu ; Xiaolong Zhang 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2018
卷号：8
期号：1
页码：5372
DOI：10.1038/s41598-018-23191-y
语种：English
出版社：Springer Nature
摘要：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.