PICK1 Genetic Variation and Cognitive Function in Patients with Schizophrenia

Chen, Yi-Ting; Lin, Chih-Chien; Huang, Chiung-Hsien; Liang, Wen‐Miin; Lane, Hsien‐Yuan

doi:10.1038/s41598-017-01975-y

Cited by 10 publications

(6 citation statements)

References 60 publications

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“…Last but not the least, the RBANS has five domains including immediate memory, attention, language, visuospatial/ constructional, and delayed memory. However, in fact, there are more cognitive domains such as executive function, working memory [43], emotional management, and facial emotion perception [44–45]. In the future study, more cognitive domains should be examined and the different ethnic population should be recruited to confirm our findings.…”

Section: Discussionmentioning

confidence: 70%

FOXP2 contributes to the cognitive impairment in chronic patients with schizophrenia

Lang

Zhang

Song

et al. 2019

Aging

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The forkhead-box P2 (FOXP2), involving in language and memory function, has been identified as susceptibility to schizophrenia. However, no study examined the role of FOXP2 on cognitive impairment in schizophrenia. Total 1106 inpatients with schizophrenia and 404 controls were recruited and genotyped. Among them, 867 patients and 402 controls were assessed through the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). SHEsis software was used to investigate the association of FOXP2 rs10447760 with schizophrenia, followed by logistic regression. The model of covariance (ANCOVA) and multivariate analysis were conducted to investigate the effect of FOXP2 rs10447760 on cognitive impairment in schizophrenia. No differences in the genotypic and allelic frequencies of the FOXP2 rs10447760 were found between patients and controls (both p> 0.05). Except for the visuospatial/constructional score (p > 0.05), other five RBANS scores were lower in patients compared to controls (all p < 0.0001). Interestingly, we found immediate memory score was lower in patients carrying genotype CT compared to genotype CC (F=5.19, p=0.02), adjusting for confounding data. Our study suggested that FOXP2 rs10447760 has no effect on the susceptibility to schizophrenia, while it may be associated with its cognitive impairment, especially immediate memory in chronic schizophrenia.

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Section: Discussionmentioning

confidence: 70%

FOXP2 contributes to the cognitive impairment in chronic patients with schizophrenia

Lang

Zhang

Song

et al. 2019

Aging

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“…The PICK1 gene has been mapped to chromosome 22q13.1 (10), and is identified to play a role in conferring susceptibility to schizophrenia (8, 28). In a recent study, Chen et al (29) explored the role of polymorphisms of PICK1 gene (rs2076369, rs3952) in cognitive functions in schizophrenic patients. They enrolled 302 patients and analyzed the differences of cognitive functions and clinical symptoms among different genetic groups.…”

Section: Discussionmentioning

confidence: 99%

Genetic Analysis of PICK1 Gene in Alzheimer's Disease: A Study for Finding a New Gene Target

Chen

Shen

et al. 2019

Front. Neurol.

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Background: Alzheimer's disease (AD) is a neurodegenerative disease with no effective treatment. Researchers have focused on exploring biomarkers for its early diagnosis, especially on finding a new gene target. Recent studies have shown that protein interacting with C-kinase-1(PICK1) is related to AD through regulating hippocampal synaptic plasticity. PICK1 gene polymorphisms have been identified in psychological and other related disorders.Methods: This study included 133 sporadic AD patients and 173 healthy controls. All coding exons and intron-exon boundaries of the PICK1 gene were amplified by polymerase chain reaction (PCR), which were subsequently sequenced and analyzed.Results: This is the first genetic association study to investigate the association between PICK1 gene and AD risk in Chinese Han population. Seven single nucleotide polymorphisms (SNPs) were found in our research (rs397780637, rs713729, rs2076369, rs58230476, rs7289911, rs149474436; and rs146770324 for patient M1659 only). Frequencies of the T allele (p = 0.002; OR, 0.083; 95%CI, 0.011–0.634) and TT/TC genotypes (p = 0.001) of rs149474436 were lower in AD patients than in the controls. The GG homozygotes of rs397780637 were found to be associated with an increased risk of AD (p = 0.018) in APOEε4 allele carriers, while the frequency of the T allele of rs149474436 was significantly lower among AD patients in APOEε4 non-carriers (p = 0.005).Conclusions: Our results suggest that PICK1 gene SNPs are associated with AD susceptibility in East Asian population, T allele of rs149474436 may play as a protective factor while the rs397780637 GG homozygotes may be associated with an increased risk of AD. Further studies should be considered in a larger cohort of patients with diverse demographics.

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“…The hypothesis named molecular heterosis implies that heterozygote subjects result in a greater or lesser impact on specific traits compared with homozygotes for a specific genetic polymorphism. Examples include smoking and cognitive functions in schizophrenic patients 57–59 . Our findings appeared in accordance with molecular heterosis.…”

Section: Discussionmentioning

confidence: 99%

Polymorphism in the LASP1 gene promoter region alters cognitive functions of patients with schizophrenia

Lin

Yang

Huang

et al. 2019

Sci Rep

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Schizophrenia’s pathogenesis remains elusive. Cognitive dysfunction is the endophenotype and outcome predictor of schizophrenia. The LIM and SH3 domain protein (LASP1) protein, a component of CNS synapses and dendritic spines, has been related to the N-methyl-D-aspartate receptor (NMDAR) dysfunction hypothesis and schizophrenia. A single-nucleotide polymorphism (rs979607) in the LASP1 gene promoter region has been also implicated in schizophrenia susceptibility. The aim of this study was to investigate the role of the LASP1 rs979607 polymorphism in the cognitive functions of patients with schizophrenia. Two hundred and ninety-one Han Taiwanese patients with schizophrenia were recruited. Ten cognitive tests and two clinical rating scales were assessed. The scores of cognitive tests were standardized to T-scores. The genotyping of the LASP1 rs979607 polymorphism was performed using TaqMan assay. Among the 291 patients, 85 were C/C homozygotes of rs979607, 141 C/T heterozygotes, and 65 T/T homozygotes, which fitted the Hardy-Weinberg equilibrium. After adjusting age, gender, and education with general linear model, the C/C homozygotes performed better than C/T heterozygotes in overall composite score (p = 0.023), Category Fluency test (representing processing speed and semantic memory) (p = 0.045), and Wechsler Memory Scale (WMS)-III backward Spatial Span test (p = 0.025), albeit without correction for multiple comparisons for the latter two individual tests. To the best of our knowledge, this is the first study suggesting that the genetic variation of LASP1 may be associated with global cognitive function, category verbal fluency, and spatial working memory of patients with schizophrenia. The finding also lends support to the NMDAR dysfunction hypothesis of schizophrenia. More studies with longitudinal designs are warranted.

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PICK1 Genetic Variation and Cognitive Function in Patients with Schizophrenia

Cited by 10 publications

References 60 publications

FOXP2 contributes to the cognitive impairment in chronic patients with schizophrenia

FOXP2 contributes to the cognitive impairment in chronic patients with schizophrenia

Genetic Analysis of PICK1 Gene in Alzheimer's Disease: A Study for Finding a New Gene Target

Polymorphism in the LASP1 gene promoter region alters cognitive functions of patients with schizophrenia

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