Yuyanan Zhang^1,2 • Hao Yan^1,2 • Jinmin Liao^1,2 • Hao Yu^1,2,3 • Sisi Jiang^1,2 • Qi Liu^1,* • Dai Zhang^1,2,4 • Weihua Yue^1,2,*
1Institute of Mental Health, Peking University Sixth Hospital, Beijing 100191, China
²Key Laboratory of Mental Health, Ministry of Health and National Clinical Research Center for Mental Disorders (Peking University), Beijing 100191, China
³Department of Psychiatry, Jining Medical University, Jining 272067, China
⁴Peking-Tsinghua Joint Center for Life Sciences and PKUIDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China

Abstract

The ZNF804A variant rs1344706 has consistently been associated with schizophrenia and plays a role in hippocampal-prefrontal functional connectivity during working memory. Whether the effect exists in the resting state and in patients with schizophrenia remains unclear. In this study, we investigated the ZNF804A polymorphism at rs1344706 in 92 schizophrenic patients and 99 healthy controls of Han Chinese descent, and used resting-state functional magnetic resonance imaging to explore the functional connectivity in the participants. We found a significant main effect of genotype on the resting-state functional connectivity (RSFC) between the hippocampus and the dorsolateral prefrontal cortex (DLPFC) in both schizophrenic patients and healthy controls. The homozygous ZNF804A rs1344706 genotype (AA) conferred a high risk of schizophrenia, and also exhibited significantly decreased resting functional coupling between the left hippocampus and right DLPFC (F(2,165) = 13.43, P < 0.001). The RSFC strength was also correlated with cognitive performance and the severity of psychosis in schizophrenia. The current findings identified the neural impact of the ZNF804A rs1344706 on hippocampal-prefrontal RSFC associated with schizophrenia.

Keywords

Schizophrenia; ZNF804A; Imaging genetics; Hippocampus; Dorsolateral prefrontal cortex

[SpringerLink]