The Effects of CACNA1C Gene Polymorphism on Spatial Working Memory in Both Healthy Controls and Patients with Schizophrenia or Bipolar Disorder

Zhang, Qiu-Mei; Shen, Qiuge; Xu, Zongbin; Chen, Min; Cheng, Lijun; Zhai, Jing; Gu, Huang; Bao, Xu; Chen, Xiongying; Wang, Keqin; Deng, Xiaoxiang; Feng, Jia‐Xun; Liu, Chuanxin; Li, Jun; Dong, Qi; Chen, Chuansheng

doi:10.1038/npp.2011.242

Cited by 89 publications

(80 citation statements)

References 42 publications

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“…This pattern seems similar to our previous results about the association between rs1006737 and the same tasks (Zhang et al, 2012). As we argued in the other article, compared with the 2-back task, the 1-back task is simpler and may involve fewer Some limitations of the current study need to be mentioned.…”

Section: Discussionsupporting

confidence: 92%

“…There appears to be a northsouth difference. Control samples from northern China showed a higher A allele frequency (0.52 in the HapMap database from Beijing, 0.54 in Xiao et al (2011) from Beijing also, and 0.51 in the current study from Shandong Province) than did a southern Chinese sample (0.46 in Zhang et al (2012) from Sichuan province and 0.49 in Li et al (2011) from Yunnan province). For patients, the frequency of the A allele in Zhang et al's study was 0.527, a frequency similar to that of controls from northern China, was also quite different from those of patients in northern China in both Xiao et al's (2011) and our study.…”

Section: Discussioncontrasting

confidence: 62%

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Evidence of IQ-Modulated Association Between ZNF804A Gene Polymorphism and Cognitive Function in Schizophrenia Patients

Chen

Zhai

et al. 2012

Neuropsychopharmacol

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ZNF804A gene polymorphism rs1344706 has been suggested as the most compelling case of a candidate gene for schizophrenia by a genome-wide association study and several replication studies. The current study of 570 schizophrenia patients and 448 controls again found significantly different genotype frequencies of rs1344706 between patients and controls. More important, we found that this association was modulated by IQ, with a stronger association among individuals with relatively high IQ, which replicated results of Walters et al, 2010. We further examined whether this IQ-modulated association also existed between the SNP and the intermediate phenotypes (working memory and executive functions) of schizophrenia. Data were available from an N-back task (366 patients and 414 controls) and the attention network task (361 patients and 416 controls). We found that the SNP and IQ had significant interaction effects on the intermediate phenotypes for patients, but not for controls. The disease risk allele was associated with poorer cognitive function in patients with high IQ, but better cognitive function in patients with low IQ. Together, these results indicated that IQ may modulate the role of rs1344706 in the etiology of both schizophrenia and its cognitive impairments, and pointed to the necessity of considering general cognitive function as indexed by IQ in the future studies of genetic bases of schizophrenia.

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Section: Discussionsupporting

confidence: 92%

Section: Discussioncontrasting

confidence: 62%

Evidence of IQ-Modulated Association Between ZNF804A Gene Polymorphism and Cognitive Function in Schizophrenia Patients

Chen

Zhai

et al. 2012

Neuropsychopharmacol

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“…The sample used in this study has been described in published articles Zhang et al, 2012;Zhu et al, 2013). Briefly, it consisted of 580 patients with SCZ and 720 healthy controls.…”

Section: Study I: the Behavior Studymentioning

confidence: 99%

“…All tasks have been introduced in our previous studies Zhang et al, 2012;Zhu et al, 2013). Briefly, IQ was tested with Wechsler Adult Intelligence Scale-Revised, which was individually administered on paper and pencil.…”

Section: Study I: the Behavior Studymentioning

confidence: 99%

Evidence for the Contribution of NOS1 Gene Polymorphism (rs3782206) to Prefrontal Function in Schizophrenia Patients and Healthy Controls

Zhang¹,

Chen

et al. 2014

Neuropsychopharmacol

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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 ¼ 0.005), the 2-back task (P ¼ 0.049), the AY condition of the dot-pattern expectancy (DPX) task (P ¼ 0.001), and the conflict effect of the attention network (ANT) test (Po0.001 for RT differences and P ¼ 0.002 for RT ratio) and interaction effects with diagnosis on the BX condition of the DPX (P ¼ 0.009), the AY condition of the DPX (Po0.001), and the Stroop conflict effect (P ¼ 0.003 for RT differences and P ¼ 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 ¼ 0.025; BX, P ¼ 0.017; AY, Po0.001; ANT conflict effect (RT differences), P ¼ 0.005; Stroop conflict effect (RT differences), P ¼ 0.019) and three measures for the controls ( for the 2-back task, P ¼ 0.042; for the ANT conlict effect (RT differences), P ¼ 0.013; for the ANT conflict effect (RT ratios), P ¼ 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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“…Although WM impairments were previously probed in SZ and BPD, comparisons across disorders have yielded inconsistent findings and the relationships between cognitive and clinical symptom domains across the psychotic variations of the disorders remain unclear (Hamilton et al, 2009;Mayer and Park, 2012;Milanovic and Vangel, 2012;Zhang et al, 2012). Discrepancy in previous studies may be due to a heterogeneous patient group and/or differences in specific task demands of the cognitive measures employed.…”

Section: Introductionmentioning

confidence: 99%

Impairments of Working Memory in Schizophrenia and Bipolar Disorder: the Effect of History of Psychotic Symptoms and Different Aspects of Cognitive Task Demands

Hewedi

Frydecka

Moustafa

2015

European Psychiatry

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Comparisons of cognitive impairments between schizophrenia (SZ) and bipolar disorder (BPD) have produced mixed results. We applied different working memory (WM) measures (Digit Span Forward and Backward, Short-delay and Long-delay CPT-AX, N-back) to patients with SZ (n = 23), psychotic BPD (n = 19) and non-psychotic BPD (n = 24), as well as to healthy controls (HC) (n = 18) in order to compare the level of WM impairments across the groups. With respect to the less demanding WM measures (Digit Span Forward and Backward, Short-delay CPT-AX), there were no between group differences in cognitive performance; however, with respect to the more demanding WM measures (Long-delay CPT-AX, N-back), we observed that the groups with psychosis (SZ, psychotic BPD) did not differ from one another, but performed poorer than the group without a history of psychosis (non-psychotic BPD). A history of psychotic symptoms may influence cognitive performance with respect to WM delay and load effects as measured by Long-delay CPT-AX and N-back tests, respectively. We observed a positive correlation of WM performance with antipsychotic treatment and a negative correlation with depressive symptoms in BPD and with negative symptoms in SZ subgroup. Our study suggests that WM dysfunctions are more closely related to a history of psychosis than to the diagnostic categories of SZ and BPD described by psychiatric classification systems.

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The Effects of CACNA1C Gene Polymorphism on Spatial Working Memory in Both Healthy Controls and Patients with Schizophrenia or Bipolar Disorder

Cited by 89 publications

References 42 publications

Evidence of IQ-Modulated Association Between ZNF804A Gene Polymorphism and Cognitive Function in Schizophrenia Patients

Evidence of IQ-Modulated Association Between ZNF804A Gene Polymorphism and Cognitive Function in Schizophrenia Patients

Evidence for the Contribution of NOS1 Gene Polymorphism (rs3782206) to Prefrontal Function in Schizophrenia Patients and Healthy Controls

Impairments of Working Memory in Schizophrenia and Bipolar Disorder: the Effect of History of Psychotic Symptoms and Different Aspects of Cognitive Task Demands

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