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Evidence for the Contribution of NOS1 Gene Polymorphism (rs3782206) to Prefrontal Function in Schizophrenia Patients and Healthy Controls
Zhang Z.1; Chen X.1; Yu P.1; Zhang Q.3; Sun X.1; Gu H.1; Zhang H.7; Zhai J.3; Chen M.3; Du B.1; Deng X.1; Ji F.3; Wang C.4; Xiang Y.4; Li D.5; Wu H.2; Li J.1; Dong Q.1; Chen C.6
Source PublicationNeuropsychopharmacology
ISSN1740634X 0893133X

Nitric oxide (NO), a gaseous neurotransmitter, has been implicated in the pathogenesis of schizophrenia. Accordingly, several polymorphisms of the gene that codes for the main NO-producing enzyme, the nitric oxide synthase 1 (NOS1), have been found to convey a risk for schizophrenia. This study examined the role of NOS1 gene polymorphisms in cognitive functions and related neural mechanism. First, with a sample of 580 schizophrenia patients and 720 healthy controls, we found that rs3782206 genotype had main effects on the 1-back task (P=0.005), the 2-back task (P=0.049), the AY condition of the dot-pattern expectancy (DPX) task (P=0.001), and the conflict effect of the attention network (ANT) test (P<0.001 for RT differences and P=0.002 for RT ratio) and interaction effects with diagnosis on the BX condition of the DPX (P=0.009), the AY condition of the DPX (P<0.001), and the Stroop conflict effect (P=0.003 for RT differences and P=0.038 for RT ratio). Simple effect analyses further showed that the schizophrenia risk allele (T) of rs3782206 was associated with poorer performance in five measures for the patients (1-back, P=0.025; BX, P=0.017; AY, P<0.001; ANT conflict effect (RT differences), P=0.005; Stroop conflict effect (RT differences), P=0.019) and three measures for the controls (for the 2-back task, P=0.042; for the ANT conlict effect (RT differences), P=0.013; for the ANT conflict effect (RT ratios), P=0.028). Then, with a separate sample of 78 healthy controls, we examined the association between rs3782206 and brain activation patterns during the N-back task and the Stroop task. Whole brain analyses found that the risk allele carriers showed reduced activation at the right inferior frontal gyrus (IFG) during both tasks. Finally, we examined functional connectivity seeded from the right IFG to the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex under three conditions (the N-back task, the Stroop task, and the resting state). Results showed reduced connectivity with the DLPFC for the risk allele carriers mainly in the Stroop task and the resting state. Taken together, results of this study strongly suggested a link between NOS1 gene polymorphism at rs3782206 and cognitive functions and their neural underpinnings at the IFG. These results have important implications for our understanding of the neural mechanism underlying the association between NOS1 gene polymorphism and schizophrenia.

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Indexed BySCI
WOS Research AreaNeurosciences & Neurology ; Pharmacology & Pharmacy ; Psychiatry
WOS SubjectNeurosciences ; Pharmacology & Pharmacy ; Psychiatry
WOS IDWOS:000352968100009
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Cited Times [WOS]:14   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Affiliation1.Beijing Normal University
2.Shengli Petroleum Administration Bureau
3.Jining Medical University
4.Beijing An Ding Hospital, Capital Medical University
5.Duke University
6.University of California System
7.Tianjin University
8.Macau University of Science and Technology
9.Ministry of Education China
Recommended Citation
GB/T 7714
Zhang Z.,Chen X.,Yu P.,et al. Evidence for the Contribution of NOS1 Gene Polymorphism (rs3782206) to Prefrontal Function in Schizophrenia Patients and Healthy Controls[J]. Neuropsychopharmacology,2015,40(6):1383-1394.
APA Zhang Z..,Chen X..,Yu P..,Zhang Q..,Sun X..,...&Chen C..(2015).Evidence for the Contribution of NOS1 Gene Polymorphism (rs3782206) to Prefrontal Function in Schizophrenia Patients and Healthy Controls.Neuropsychopharmacology,40(6),1383-1394.
MLA Zhang Z.,et al."Evidence for the Contribution of NOS1 Gene Polymorphism (rs3782206) to Prefrontal Function in Schizophrenia Patients and Healthy Controls".Neuropsychopharmacology 40.6(2015):1383-1394.
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