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Glucose disturbances, cognitive deficits and white matter abnormalities in first-episode drug-naive schizophrenia
Xiangyang Zhang1,2,3; Mi Yang4,5; Xiangdong Du6; Wei Liao5; Dachun Chen7; Fengmei Fan7; Meihong Xiu7; Qiufang Jia6; Yuping Ning3; Xingbing Huang3; Fengchun Wu3; Jair C. Soares8; Bo Cao8; Li Wang1; Huafu Chen5
First AuthorXiangyang Zhang
Corresponding AuthorZhang, Xiangyang( ; Chen, Huafu(
Correspondent (xiangyang zhang) ; (huafu chen)
Contribution Rank1

Objective: Post-traumatic stress disorder (PTSD) is a trauma- and stress-related psychiatric syndrome that occurs after exposure to extraordinary stressors. The neurotransmitter dopamine (DA) plays important roles in neurobiological processes like reward and stress, and a link between PTSD and the dopaminergic system has been reported. Thus, the investigation of an association between PTSD and gene–gene interaction (epistasis) within dopaminergic genes could uncover the genetic basis of dopamine-related PTSD symptomatology and contribute to precision medicine.
Methods: We genotyped seven single nucleotide polymorphisms (SNPs) of three dopaminergic genes DRD2/ANNK1 (rs1800497 and rs1801028), COMT (rs6269, rs4633, rs4818 and rs4680) and DBH (rs1611115), in a Chinese predominantly adult cohort that had been exposed to an earthquake (156 PTSD cases and 978 controls). Results: Statistical genetics analysis identified a DRD2/ANNK1–COMT interaction (rs1800497 × rs6269), which is associated with PTSD diagnosis (Pinteraction = 0.0008055
and Pcorrected = 0.0169155). Single-variant and haplotype-based subset analyses showed that rs1800497 modulates the association directions of both the rs6269 G allele and the rs6269-rs4633-rs4818-rs4680 haplotype G-C-G-G. The interaction (rs1800497 × rs6269) was replicated in a Chinese young female cohort (32 cases and 581 controls, Pinteraction = 0.01329).
Conclusions: Rs1800497 is related to the DA receptor D2 density and
rs6269-rs4633-rs4818-rs4680 haplotypes affect the catechol O-methyltransferase level and enzyme activity. Thus, the interaction was inferred to be at protein–protein and DA activity level. The genotype combinations of the two SNPs indicate a potential origin of DA homeostasis abnormalities in PTSD development.

Source PublicationMolecular Psychiatry
Indexed BySCI
WOS Research AreaBiochemistry & Molecular Biology ; Neurosciences & Neurology ; Psychiatry
WOS SubjectBiochemistry & Molecular Biology ; Neurosciences ; Psychiatry
WOS IDWOS:000608499700016
Citation statistics
Cited Times:13[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Affiliation1.CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
2.Department of Psychology, University of Chinese Academy of Sciences, Beijing, China
3.The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, China
4.Department of Stomatology, the Fourth People’s Hospital of Chengdu, Chengdu, China
5.Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China
6.Suzhou Psychiatric Hospital, The Affiliated Guangji Hospital of Soochow University, Suzhou, China
7.Psychiatry Research Center, Beijing HuiLongGuan Hospital, Peking University, Beijing, China
8.Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, Texas, USA
First Author AffilicationInstitute of Psychology, Chinese Academy of Sciences
Recommended Citation
GB/T 7714
Xiangyang Zhang,Mi Yang,Xiangdong Du,et al. Glucose disturbances, cognitive deficits and white matter abnormalities in first-episode drug-naive schizophrenia[J]. Molecular Psychiatry,2020,25(12):3220–3230.
APA Xiangyang Zhang.,Mi Yang.,Xiangdong Du.,Wei Liao.,Dachun Chen.,...&Huafu Chen.(2020).Glucose disturbances, cognitive deficits and white matter abnormalities in first-episode drug-naive schizophrenia.Molecular Psychiatry,25(12),3220–3230.
MLA Xiangyang Zhang,et al."Glucose disturbances, cognitive deficits and white matter abnormalities in first-episode drug-naive schizophrenia".Molecular Psychiatry 25.12(2020):3220–3230.
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