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2.
J Natl Cancer Inst ; 113(4): 471-480, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33094348

RESUMO

BACKGROUND: Induction chemotherapy (IC) followed by concurrent chemoradiotherapy is the mainstay treatment for patients with locoregionally advanced nasopharyngeal carcinoma. However, some patients obtain little benefit and experience unnecessary toxicities from IC. We intended to develop a gene-expression signature that can identify beneficiaries of IC. METHODS: We screened chemosensitivity-related genes by comparing gene-expression profiles of patients with short-term tumor response or nonresponse to IC (n = 95) using microarray analysis. Chemosensitivity-related genes were quantified by digital expression profiling in a training cohort (n = 342) to obtain a gene signature. We then validated this gene signature in the clinical trial cohort (n = 187) and an external independent cohort (n = 240). Tests of statistical significance are 2-sided. RESULTS: We identified 43 chemosensitivity-related genes associated with the short-term tumor response to IC. In the training cohort, a 6-gene signature was developed that was highly accurate at predicting the short-term tumor response to IC (area under the curve [AUC] = 0.87, sensitivity = 87.5%, specificity = 75.6%). We further found that IC conferred failure-free survival benefits only in patients in the benefit group (hazard ratio [HR] = 0.54, 95% confidence interval [CI] = 0.34 to 0.87; P = .01) and not on those in the no-benefit group (HR = 1.25, 95% CI = 0.62 to 2.51; P = .53). In the clinical trial cohort, the 6-gene signature was also highly accurate at predicting the tumor response (AUC = 0.82, sensitivity = 87.5%, specificity = 71.8%) and indicated failure-free survival benefits. In the external independent cohort, similar results were observed. CONCLUSIONS: The 6-gene signature can help select beneficiaries of IC and lay a foundation for a more individualized therapeutic strategy for locoregionally advanced nasopharyngeal carcinoma patients.


Assuntos
Expressão Gênica , Quimioterapia de Indução , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/genética , Adulto , Idoso , Área Sob a Curva , Estudos de Coortes , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Sensibilidade e Especificidade , Resultado do Tratamento
3.
Cancer Commun (Lond) ; 40(12): 721-737, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33038291

RESUMO

BACKGROUND: Epigenetic regulation plays an important role in the development and progression of nasopharyngeal carcinoma (NPC). However, the epigenetic mechanisms underlying NPC metastasis remains poorly understood. We aimed to find functional genes which regulate the metastasis of NPC and identify therapeutic targets for NPC treatment. METHODS: Bisulfite pyrosequencing was used to analyze zinc finger protein 582 (ZNF582) methylation in NPC tissues and cell lines. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting were used to determine the expression of ZNF582. In vitro and in vivo experiments were performed to evaluate the biological function of ZNF582 in NPC. ZNF582-targeting genes were identified by chromatin immunoprecipitation sequencing (ChIP-seq) and were confirmed by ChIP-qPCR and luciferase assay. RESULTS: ZNF582 promoter was hypermethylated in NPC, and both the mRNA and protein levels of ZNF582 were down-regulated in NPC tissues and cell lines. The restoration of ZNF582 inhibited NPC migration, invasion, and metastasis, while the knockdown of ZNF582 promoted NPC migration, invasion, and metastasis in vitro and in vivo. ZNF582 directly regulated the transcription and expression of adhesion molecules Nectin-3 and NRXN3. Both Nectin-3 and NRXN3 were identified as functional targets of ZNF582, and the restoration or abrogation of these genes reversed the tumor suppressor effect of ZNF582 in NPC metastasis. CONCLUSIONS: ZNF582 acts as a tumor suppressor gene in NPC by regulating the transcription and expression of adhesion molecules Nectin-3 and NRXN3, which may provide novel therapeutic targets for NPC treatment.


Assuntos
Metilação de DNA , Fatores de Transcrição Kruppel-Like/genética , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Nectinas/genética , Proteínas do Tecido Nervoso/genética , Linhagem Celular Tumoral , Epigênese Genética , Células HEK293 , Humanos , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Regiões Promotoras Genéticas
4.
Cancer Sci ; 111(6): 1991-2003, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32232887

RESUMO

Alternative polyadenylation (APA), which induces shortening of the 3'-UTR, is emerging as an important feature in cancer development and progression. Nevertheless, the effects and mechanisms of APA-induced 3'-UTR shortening in nasopharyngeal carcinoma (NPC) remain largely unclear. Fibronectin type III domain containing 3B (FNDC3B) tended to use proximal polyadenylation site and produce shorter 3'-UTR according to our previous sequencing study. Herein, we found that FNDC3B with shorter 3'-UTR could escape from miRNA-mediated gene repression, and caused its increased expression in NPC. Knocking down of FNDC3B inhibited NPC cell proliferation, migration, invasion, and metastasis in vitro and in vivo. Overexpression of FNDC3B, especially those with shorter 3'-UTR, promoted NPC progression. Furthermore, the mechanism study revealed that FNDC3B could bind to and stabilize myosin heavy chain 9 (MYH9) to activate the Wnt/ß-catenin signaling pathway. In addition, MYH9 could reverse the inhibitory effects of FNDC3B knockdown in NPC. Altogether, our results suggested that the 3'-UTR shortening of FNDC3B mRNA mediated its overexpression in NPC and promoted NPC progression by targeting MYH9. This newly identified FNDC3B-MYH9-Wnt/ß-catenin axis could represent potential targets for individualized treatment in NPC.


Assuntos
Fibronectinas/metabolismo , Regulação Neoplásica da Expressão Gênica/fisiologia , Cadeias Pesadas de Miosina/metabolismo , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Regiões 3' não Traduzidas , Animais , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Fibronectinas/genética , Xenoenxertos , Humanos , Camundongos , MicroRNAs , Cadeias Pesadas de Miosina/genética , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Via de Sinalização Wnt/fisiologia
5.
Cells ; 9(3)2020 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-32120844

RESUMO

Epigenetic regulation plays an important role in the development and progression of nasopharyngeal carcinoma (NPC), but the epigenetic mechanisms underlying NPC metastasis remain poorly understood. Here, we demonstrate that hypermethylation of the UCHL1 promoter leads to its downregulation in NPC. Restoration of UCHL1 inhibited the migration and invasion of NPC cells in vitro and in vivo, and knockdown of UCHL1 promoted NPC cell migration and invasion in vitro and in vivo. Importantly, we found that UCHL1 interacts with CTTN, and may function as a ligase promoting CTTN degradation by increasing K48-linked ubiquitination of CTTN. Additionally, restoration of CTTN in NPC cells that overexpressed UCHL1 rescued UCHL1 suppressive effects on NPC cell migration and invasion, which indicated that CTTN is a functional target of UCHL1 in NPC. Our findings revealed that UCHL1 acts as a tumor suppressor gene in NPC and thus provided a novel therapeutic target for NPC treatment.


Assuntos
Cortactina/metabolismo , Metilação de DNA/genética , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patologia , Proteólise , Ubiquitina Tiolesterase/genética , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Humanos , Lisina/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Metástase Neoplásica , Regiões Promotoras Genéticas , Ligação Proteica , Ubiquitina Tiolesterase/metabolismo , Ubiquitinação
6.
J Immunother Cancer ; 7(1): 298, 2019 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-31722750

RESUMO

BACKGROUND: Immunotherapy, especially immune checkpoint inhibition, has provided powerful tools against cancer. We aimed to detect the expression of common immune checkpoints and evaluate their prognostic values in nasopharyngeal carcinoma (NPC). METHODS: The expression of 9 immune checkpoints consistent with 13 features was detected in the training cohort (n = 208) by immunohistochemistry and quantified by computational pathology. Then, the LASSO cox regression model was used to construct an immune checkpoint-based signature (ICS), which was validated in a validation cohort containing 125 patients. RESULTS: High positive expression of PD-L1 and B7-H4 was observed in tumour cells (TCs), whereas PD-L1, B7-H3, B7-H4, IDO-1, VISTA, ICOS and OX40 were highly expressed in tumour-associated immune cells (TAICs). Eight of the 13 immune features were associated with patient overall survival, and an ICS classifier consisting of 5 features (B7-H3TAIC, IDO-1TAIC, VISTATAIC, ICOSTAIC, and LAG3TAIC) was established. Patients with high-risk scores in the training cohort had shorter overall (P < 0.001), disease-free (P = 0.002), and distant metastasis-free survival (P = 0.004), which were confirmed in the validation cohort. Multivariate analysis revealed that the ICS classifier was an independent prognostic factor. A combination of the ICS classifier and TNM stage had better prognostic value than the TNM stage alone. In addition, the ICS classifier was significantly associated with survivals in patients with high EBV-DNA load. CONCLUSIONS: We determined the expression status of nine immune checkpoints consistent with 13 features in NPC and further constructed an ICS prognostic model, which might add prognostic value to the TNM staging system.


Assuntos
Carcinoma Nasofaríngeo/imunologia , Neoplasias Nasofaríngeas/imunologia , Antígenos CD/imunologia , Antígenos B7/imunologia , Antígeno B7-H1/imunologia , Biologia Computacional , Receptor Celular 2 do Vírus da Hepatite A/imunologia , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/imunologia , Proteína Coestimuladora de Linfócitos T Induzíveis/imunologia , Estimativa de Kaplan-Meier , Carcinoma Nasofaríngeo/mortalidade , Neoplasias Nasofaríngeas/mortalidade , Estadiamento de Neoplasias , Prognóstico , Receptores OX40/imunologia , Inibidor 1 da Ativação de Células T com Domínio V-Set/imunologia
7.
Neoplasia ; 21(3): 311-321, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30772768

RESUMO

DNA methylation is an important epigenetic change in carcinogenesis. However, the function and mechanism of DNA methylation dysregulation in nasopharyngeal carcinoma (NPC) is still largely unclear. Our previous genome-wide microarray data showed that NFAT1 is one of the most hypermethylated transcription factor genes in NPC tissues. Here, we found that NFAT1 hypermethylation contributes to its down-regulation in NPC. NFAT1 overexpression inhibited cell migration, invasion, and epithelial-mesenchymal transition in vitro and tumor metastasis in vivo. We further established that the tumor suppressor effect of NFAT1 is mediated by its inactivation of ITGA6 transcription. Our findings suggest the significance of activating NFAT1/ITGA6 signaling in aggressive NPC, defining a novel critical signaling mechanism that drives NPC invasion and metastasis and providing a novel target for future personalized therapy.


Assuntos
Metilação de DNA , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Integrina alfa6/genética , Fatores de Transcrição NFATC/genética , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patologia , Ativação Transcricional , Linhagem Celular Tumoral , Epigênese Genética , Perfilação da Expressão Gênica , Humanos , Metástase Linfática , Estadiamento de Neoplasias , Interferência de RNA , Transcriptoma
8.
Cancer Res ; 79(4): 747-759, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30573520

RESUMO

Altered DNA methylation is a key feature of cancer, and aberrant methylation is important in nasopharyngeal carcinoma (NPC) development. However, the methylation mechanisms underlying metastasis of NPC remain unclear. Analyzing data from public databases and conducting our own experiments, we report here that promoter hypermethylation of SHISA3 is common and contributes to the downregulation of this gene in many types of tumors, including NPC. SHISA3 suppressed NPC cell invasion and metastasis in vitro and in vivo by impeding the E3 ubiquitin ligase tripartite motif containing 21 (TRIM21)-mediated ubiquitination and degradation small G protein signaling modulator 1 (SGSM1) and by inhibiting the MAPK pathway activation. Silencing SGSM1 abrogated the inhibitory effect of SHISA3 on NPC cell migration and invasion. This newly identified SHISA3-TRIM21-SGSM1 axis could be a novel therapeutic target in NPC. SIGNIFICANCE: These findings highlight the mechanism by which a newly identified tumor suppressor SHISA3 suppresses invasion and metastasis of nasopharyngeal carcinoma.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intracelular/química , Proteínas de Membrana/química , Neoplasias Nasofaríngeas/patologia , Animais , Apoptose , Proteínas Reguladoras de Apoptose/genética , Biomarcadores Tumorais , Movimento Celular , Proliferação de Células , Regulação para Baixo , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Metástase Linfática , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Prognóstico , Estabilidade Proteica , Transdução de Sinais , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Theranostics ; 8(20): 5676-5689, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30555573

RESUMO

Long noncoding RNAs (lncRNAs) play an important role in the development and progression of cancers. However, the clinical significances of lncRNAs and their functions and mechanisms in nasopharyngeal carcinoma (NPC) remain largely unclear. Methods: Quantitative RT-PCR was used to determine DANCR expression and Kaplan-Meier curves were used to evaluate its prognostic value. RNA sequencing followed by bioinformatic analysis was performed to determine the potential function of DANCR. In vitro and in vivo experiments were conducted to investigate its biological effects. DANCR-interacting proteins were identified by RNA pull-down assay followed by mass spectrometry and western blotting, and then confirmed by RNA immunoprecipitation (RIP) assays. Results: Our previous microarray analysis identified a metastasis-associated lncRNA DANCR. Here, we found that DANCR was upregulated in NPC, especially in those with lymph lode metastasis, and its upregulation could predict poor survival. We then constructed a prognostic predictive model. RNA sequencing followed by bioinformatic analysis revealed that DANCR was responsible for NPC metastasis and hypoxia phenotype. Functional studies showed that DANCR promoted NPC cell invasion and metastasis in vitro and in vivo. Further investigation suggested that DANCR could increase HIF-1α mRNA stability through interacting with the NF90/NF45 complex. Additionally, overexpression of HIF-1α in DANCR knockdown cells restored its suppressive effects on NPC cell migration and invasion. Conclusions: Taken together, our results suggest that DANCR acts as a prognostic biomarker and increases HIF-1α mRNA stability by interacting with NF90/NF45, leading to metastasis and disease progression of NPC.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/fisiopatologia , Proteína do Fator Nuclear 45/metabolismo , Proteínas do Fator Nuclear 90/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Western Blotting , Linhagem Celular Tumoral , Biologia Computacional , Modelos Animais de Doenças , Progressão da Doença , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Imunoprecipitação , Espectrometria de Massas , Camundongos Endogâmicos BALB C , Camundongos Nus , Carcinoma Nasofaríngeo/secundário , Prognóstico , Ligação Proteica , Multimerização Proteica , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sequência de RNA
10.
Front Genet ; 9: 725, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30745909

RESUMO

Schizophrenia is a complex psychiatric disorder with high genetic heterogeneity, however, the contribution of rare mutations to the disease etiology remains to be further elucidated. We herein performed exome sequencing in a Han Chinese schizophrenia family and identified a missense mutation (c.6724C>T, p.R2242C) in the teneurin transmembrane protein 4 (TENM4) gene in the SCZD2 locus, a region previously linked to schizophrenia at 11q14-21. The mutation was confirmed to co-segregate with the schizophrenia phenotype in the family. Subsequent investigation of TENM4 exons 31, 32, and 33 adjacent to the p.R2242C mutation revealed two additional missense mutations in 120 sporadic schizophrenic patients. Residues mutated in these mutations, which are predicted to be deleterious to protein function, were highly conserved among vertebrates. These rare mutations were not detected in 1000 Genomes, NHLBI Exome Sequencing Project databases, or our in-house 1136 non-schizophrenic control exomes. Analysis of RNA-Seq data showed that TENM4 is expressed in the brain with high abundance and specificity. In line with the important role of TENM4 in central nervous system development, our findings suggested that increased rare variants in TENM4 could be associated with schizophrenia, and thus TENM4 could be a novel candidate gene for schizophrenia in the SCZD2 locus.

11.
Psychiatry Res ; 256: 225-227, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28646786

RESUMO

This study explored specificity and visual perspective of mental time travel in schizophrenia. Fifteen patients with schizophrenia and 18 controls were recruited. Participants were asked to recall or imagine specific events according to cue words. Results showed that schizophrenia patients generated fewer specific events than controls, the recalled events were more specific than imagined events. Schizophrenia adopted less field perspective and more observer perspective than controls. These results suggested that patients with schizophrenia were impaired in mental time travel both in specificity and visual perspective. Further studies are needed to identify the underlying mechanisms.


Assuntos
Imaginação , Rememoração Mental , Esquizofrenia/fisiopatologia , Psicologia do Esquizofrênico , Percepção Visual , Adulto , Estudos de Casos e Controles , Sinais (Psicologia) , Feminino , Humanos , Masculino , Adulto Jovem
12.
Psychiatry Res ; 237: 188-95, 2016 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-26833279

RESUMO

Research on the relationship between insight and social cognition, in particular Theory of Mind (ToM), in schizophrenia has yielded mixed findings to date. Very few studies, however, have assessed both clinical insight and cognitive insight when examining their relationships with ToM in schizophrenia. The current study thus investigated the relationship between clinical insight, cognitive insight, and ToM in a sample of 56 patients with schizophrenia and 30 healthy controls. Twenty-seven patients were classified as low in clinical insight according to their scores on the 'insight' item (G12) of the Positive and Negative Syndrome Scale (PANSS). Moreover, cognitive insight and ToM were assessed with the Beck Cognitive Insight Scale (BCIS) and the Yoni task, respectively. The results indicated that patients with poor clinical insight performed worse on tasks of second-order cognitive and affective ToM, while the ToM performance of patients with high clinical insight was equivalent to that of healthy controls. Furthermore, while clinical insight was correlated with ToM and clinical symptoms, cognitive insight did not correlate with clinical insight, ToM, or clinical symptoms. Clinical insight thus appears to be an important factor related to ToM in schizophrenia.


Assuntos
Conscientização/fisiologia , Metacognição/fisiologia , Esquizofrenia/fisiopatologia , Teoria da Mente/fisiologia , Adulto , Feminino , Humanos , Masculino , Adulto Jovem
13.
Psychiatry Res ; 216(2): 161-7, 2014 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-24589449

RESUMO

Very few studies have examined physical and social anhedonia across the spectrum of schizophrenia. In the present study, we recruited three groups of participants (n=84 in each group): patients with schizophrenia, schizotypy and non-schizotypy as assessed by the Schizotypal Personality Questionnaire (SPQ). All participants completed the self-reported trait anhedonia scales (the Revised Physical Anhedonia Scale and the Social Anhedonia Scale). The clinical symptoms of schizophrenia patients were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Scale for Assessment of Negative Symptoms (SANS). We found that the three groups differed in both physical and social anhedonia. The schizotypy group reported higher levels of physical anhedonia than the non-schizotypy group, and the patient group reported higher levels of physical anhedonia than the schizotypy group. For social anhedonia, the non-schizotypy group differed significantly from both the schizotypy and the patient group, while no significant difference was found between the last two groups. Our findings show that individuals with schizotypy exhibits similar social but not physical anhedonia compared with patients with schizophrenia, which further suggests that decreased pleasure experiences in the social environment may be a valuable target for identification and early intervention in high-risk populations.


Assuntos
Anedonia , Esquizofrenia/fisiopatologia , Psicologia do Esquizofrênico , Transtorno da Personalidade Esquizotípica/fisiopatologia , Transtorno da Personalidade Esquizotípica/psicologia , Adolescente , Adulto , China , Feminino , Humanos , Masculino , Personalidade , Inventário de Personalidade , Psicometria , Autorrelato , Inquéritos e Questionários , Adulto Jovem
14.
Psych J ; 2(3): 175-82, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26271362

RESUMO

This study aimed to examine verbal and visual-spatial working memory (WM) dysfunction in patients with schizophrenia. We compared 60 patients with schizophrenia with 57 healthy controls (matched for age, educational level, and IQ) on three WM tasks. Patients with schizophrenia performed significantly more poorly than healthy controls on verbal, visual, and spatial WM tests. Moreover, WM deficits were inversely associated with both the positive and negative symptoms of the patients. Taken together, these findings suggest that there are pervasive WM impairments in patients with schizophrenia. In addition, clinical features may play a significant role in the expression of WM deficits.

15.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 28(2): 208-11, 2011 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-21462137

RESUMO

OBJECTIVE: To investigate the association between 8 polymorphisms in the catechol-O-methyl transferase gene (COMT) and schizophrenia in Yuedong-Chaoshan region of China. METHODS: Eight single nucleotide polymorphism (SNPs), namely rs4680, rs4818, rs165599, rs737865, rs2075507, rs6267, rs6269 and rs4633, in the COMT gene were genotyped in 279 schizophrenia patients and 100 healthy controls. RESULTS: There was no significant difference between any single SNP and schizophrenia. However, association might exist between haplotypes (G)-G-A-A [(rs4680)-rs165599-rs2075507-rs6269] and A-A-C-(G) [rs2075507-rs6269-rs4633-(rs6267)] and schizophrenia. CONCLUSION: In the population of Yuedong region of China, the eight SNPs (rs4680, rs4818, rs165599, rs737865, rs2075507, rs6267, rs6269 and rs4633) in the COMT gene are unlikely to play a major role in the susceptibility to schizophrenia. There might be protective haplotypes in the COMT gene against schizophrenia.


Assuntos
Catecol O-Metiltransferase/genética , Esquizofrenia/genética , Adulto , China , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Esquizofrenia/enzimologia , Adulto Jovem
16.
Psychiatry Res ; 185(3): 340-6, 2011 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-20624658

RESUMO

This study aimed to examine the subjective awareness of everyday dysexecutive function and the 'objective' executive function in individuals with schizotypal personality features. Forty-nine individuals with schizotypal personality disorder (SPD) proneness (25 negative schizotypy and 24 non-negative schizotypy were identified using cluster analysis) and 44 non-SPD individuals completed a battery of 'objective' executive function tests and a self-reported Dysexecutive Questionnaire (DEX) on everyday executive problems. The findings showed that individuals with SPD proneness including negative schizotypy and non-negative schizotypy did not have significant worse performance than non-SPD in most of 'objective' executive function tests, but self-reported significantly disproportionate more dysexecutive problems than non-SPD. Furthermore, SPD proneness, especially negative schizotypy was found to give undependable estimation on their everyday dysexecutive function while non-negative schizotypy was not. The current findings suggest that the subjective awareness of dysexecutive function may precede actual 'objective' executive function impairments in a subtype of SPD (non-negative schizotypy) and the subjective complaint of the daily dysexecutive behavior in SPD proneness, especially negative schizotypy might result from their unreliable estimation of executive function.


Assuntos
Conscientização/fisiologia , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/psicologia , Função Executiva/fisiologia , Transtorno da Personalidade Esquizotípica/complicações , Adolescente , Adulto , Análise de Variância , Feminino , Humanos , Inibição Psicológica , Intenção , Masculino , Testes Neuropsicológicos , Inventário de Personalidade , Autorrelato , Estatística como Assunto , Adulto Jovem
17.
Arch Clin Neuropsychol ; 25(7): 648-55, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20660603

RESUMO

Schizophrenia and normal aging have both been associated with structural and physiological changes in the prefrontal and temporal cortex and impairments in prospective memory (PM). This study aimed to compare PM performance in patients with schizophrenia, healthy older, and healthy younger individuals. Computerized event- and time-based PM tasks were administered to 30 patients with schizophrenia, 30 healthy older adults, and 30 healthy younger adults. The healthy older adults and patients with schizophrenia demonstrated deficits in time-based PM when compared with the healthy younger adults. However, only healthy older adults were found to be impaired in event-based PM when compared with the healthy younger adults. These findings suggest that patients with schizophrenia show a similar pattern of performance on one type but not another type of PM and provide only partial support for the accelerated aging hypothesis of schizophrenia.


Assuntos
Envelhecimento/psicologia , Transtornos da Memória/diagnóstico , Transtornos da Memória/psicologia , Esquizofrenia/diagnóstico , Psicologia do Esquizofrênico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Desempenho Psicomotor , Fatores de Tempo
18.
Schizophr Res ; 103(1-3): 229-39, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18420383

RESUMO

While a number of studies have shown that individuals with schizophrenia are impaired on various types of prospective memory, few studies have examined the relationship between subjective and objective measures of this construct in this clinical group. The purpose of the current study was to explore the relationship between computer-based prospective memory tasks and the corresponding subjective complaints in patients with schizophrenia, individuals with schizotypal personality features, and healthy volunteers. The findings showed that patients with schizophrenia demonstrated significantly poorer performance in all domains of memory function except visual memory than individuals with schizotypal personality disorder and healthy controls. More importantly, there was a significant interaction effect of prospective memory type and group. Although patients with schizophrenia were found to show significantly poorer performance on computer-based measures of prospective memory than controls, their level of subjective complaint was not found to be significantly higher. While subjective complaints of prospective memory were found to associate significantly with self-reported executive dysfunctions, significant relationships were not found between these complaints and performance on a computer-based task of prospective memory and other objective measures of memory. Taken together, these findings suggest that subjective and objective measures of prospective memory are two distinct domains that might need to be assessed and addressed separately.


Assuntos
Intenção , Rememoração Mental , Esquizofrenia/diagnóstico , Psicologia do Esquizofrênico , Adolescente , Adulto , Atenção , Feminino , Humanos , Masculino , Memória de Curto Prazo , Pessoa de Meia-Idade , Reconhecimento Visual de Modelos , Resolução de Problemas , Escalas de Graduação Psiquiátrica , Retenção Psicológica , Transtorno da Personalidade Esquizotípica/diagnóstico , Transtorno da Personalidade Esquizotípica/psicologia , Aprendizagem Verbal
19.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 22(4): 441-3, 2005 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-16086287

RESUMO

OBJECTIVE: To investigate the relationship between 1137-1140 Del GTGA in exon 1 at KCNN3 gene and schizophrenia. METHODS: The study included 289 subjects (affected 107; unaffected 182) from 95 schizophrenic trios. All subjects were collected from Han Chinese in south China and genotyped for 1137-1140 Del GTGA in KCNN3 using PCR and restriction endonuclease Dde I. All the affected patients met the CCMD-II-R criteria for schizophrenia. The haplotype-based haplotype relative risk(HHRR) and transmission/disequilibrium test(TDT) analyses were done in 95 schizophrenic trios. RESULTS: Comparative analysis on the distribution of alleles between the affected and unaffected parents(87 family trios) showed no significant difference(X(2)=0.253, P> 0.05). HHRR showed that KCNN3 gene alleles transmitted to the patients were not different from that of the non-transmitted parental alleles(X(2)=0.042, P> 0.05). TDT revealed that A(2) alleles were not preferentially transmitted to schizophrenic patients(X(2)=3.000, P=0.0833). CONCLUSION: In this study a lower frequency for 1137-1140 Del homozygote of KCNN3 gene was observed, and the HHRR and TDT analyses suggested that the 1137-1140 Del alleles of KCNN3 gene be unlikely to confer susceptibility to schizophrenia.


Assuntos
Mutação da Fase de Leitura , Desequilíbrio de Ligação/genética , Esquizofrenia/genética , Canais de Potássio Ativados por Cálcio de Condutância Baixa/genética , Adolescente , Adulto , Idoso , Criança , Saúde da Família , Feminino , Predisposição Genética para Doença/genética , Haplótipos/genética , Humanos , Masculino , Pessoa de Meia-Idade , Núcleo Familiar , Adulto Jovem
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