PMID- 32544854 OWN - NLM STAT- MEDLINE DCOM- 20210329 LR - 20210329 IS - 2213-1582 (Electronic) IS - 2213-1582 (Linking) VI - 27 DP - 2020 TI - Effect of ZNF804A gene polymorphism (rs1344706) on the plasticity of the functional coupling between the right dorsolateral prefrontal cortex and the contralateral hippocampal formation. PG - 102279 LID - S2213-1582(20)30116-9 [pii] LID - 10.1016/j.nicl.2020.102279 [doi] LID - 102279 AB - ZNF804A has now been recognized as a schizophrenia risk gene by multiple genome-wide association studies with its intronic polymorphism rs1344706 being reported as the first genome-wide significant risk variant for schizophrenia. Although the functional impact of this gene is still unknown, rs1344706's contribution to the functional coupling between the right dorsolateral prefrontal cortex (DLPFC) and the contralateral hippocampal formation (HF) has been reported by several studies. The current study tested whether the right DLPFC-left HF functional coupling showed plasticity during cognitive training (Study I) and whether rs1344706 affected the plasticity (Study II). In Study I, we conducted a randomized controlled trial with 30 subjects receiving 20 sessions of adaptive training on a memory span task (the training group) and 30 subjects practicing on a non-adaptive easy version of the same memory span task for 20 sessions (the control group). All subjects were scanned using fMRI before and after the training. Analyses of resting-state and task-state fMRI data consistently showed that the adaptive memory span training significantly strengthened the right DLPFC-left HF functional coupling. In Study II, we conducted a genetic association study with 101 subjects (combining the data from the training group in Study I with those from an additional subsequent sample of 71 subjects who received the same training and fMRI scans). Results showed that rs1344706 was significantly associated with training-induced changes in functional coupling. Subjects carrying the non-risk allele (C) of rs1344706 showed greater training-induced plasticity than the risk allele (A) homozygotes. These findings expanded our current understanding of the functional impact of the schizophrenia risk variant of ZNF804A gene and suggested that the ZNF804A gene could be used as a prospective target for future antipsychotic drugs and clinical research. CI - Copyright (c) 2020 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Zhao, Wan AU - Zhao W AD - State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, PR China. FAU - Chen, Xiongying AU - Chen X AD - The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders & Beijing Institute for Brain Disorders Center of Schizophrenia, Beijing Anding Hospital, Capital Medical University, Beijing 100088, PR China. FAU - Zhang, Qiumei AU - Zhang Q AD - State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, PR China; School of Mental Health, Jining Medical University, 45# Jianshe South Road, Jining 272013, Shandong Province, PR China. FAU - Du, Boqi AU - Du B AD - State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, PR China. FAU - Deng, Xiaoxiang AU - Deng X AD - State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, PR China. FAU - Ji, Feng AU - Ji F AD - School of Mental Health, Jining Medical University, 45# Jianshe South Road, Jining 272013, Shandong Province, PR China. FAU - Xiang, Yu-Tao AU - Xiang YT AD - Faculty of Health Sciences, University of Macau, Avenida da Universidade, Taipa, Macau, PR China. FAU - Wang, Chuanyue AU - Wang C AD - The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders & Beijing Institute for Brain Disorders Center of Schizophrenia, Beijing Anding Hospital, Capital Medical University, Beijing 100088, PR China. FAU - Dong, Qi AU - Dong Q AD - State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, PR China. FAU - Chen, Chuansheng AU - Chen C AD - Department of Psychological Science, University of California, Irvine, CA 92697, United States. FAU - Li, Jun AU - Li J AD - State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, PR China. Electronic address: lijundp@bnu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200526 PL - Netherlands TA - Neuroimage Clin JT - NeuroImage. Clinical JID - 101597070 RN - 0 (Kruppel-Like Transcription Factors) RN - 0 (ZNF804A protein, human) SB - IM MH - Adult MH - Brain Mapping MH - Female MH - Functional Laterality/*genetics MH - Genome-Wide Association Study MH - Hippocampus/*physiopathology MH - Humans MH - Kruppel-Like Transcription Factors/*genetics MH - Magnetic Resonance Imaging/methods MH - Male MH - Memory, Short-Term/physiology MH - Neural Pathways/physiopathology MH - Polymorphism, Single Nucleotide/genetics MH - Prefrontal Cortex/*physiopathology MH - Schizophrenia/genetics/physiopathology MH - Young Adult PMC - PMC7301231 OTO - NOTNLM OT - DLPFC OT - FMRI OT - Hippocampal formation OT - Plasticity OT - Working memory training OT - ZNF804A EDAT- 2020/06/17 06:00 MHDA- 2021/03/30 06:00 PMCR- 2020/05/26 CRDT- 2020/06/17 06:00 PHST- 2019/10/29 00:00 [received] PHST- 2020/05/06 00:00 [revised] PHST- 2020/05/07 00:00 [accepted] PHST- 2020/06/17 06:00 [pubmed] PHST- 2021/03/30 06:00 [medline] PHST- 2020/06/17 06:00 [entrez] PHST- 2020/05/26 00:00 [pmc-release] AID - S2213-1582(20)30116-9 [pii] AID - 102279 [pii] AID - 10.1016/j.nicl.2020.102279 [doi] PST - ppublish SO - Neuroimage Clin. 2020;27:102279. doi: 10.1016/j.nicl.2020.102279. Epub 2020 May 26.