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1.
Can J Physiol Pharmacol ; 98(1): 1-5, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31518506

RESUMO

This study analyzed risk factors for anxiety and depression in 714 patients who received surgery for endometrial cancer. Our data indicate that the incidence of postoperative anxiety and depression in 714 patients with endometrial cancer was 15.55% and 32.77%, respectively. Univariate and logistic regression analysis showed postoperative pain (odds ratio (OR) = 3.166, P = 0.000) and combined liver disease (OR = 2.318, P = 0.001) were independent risk factors for postoperative anxiety. Additionally, CD4+/CD8+ (OR = 0.513, P = 0.042) and natural killer (NK) cell ratios (OR = 0.692, P = 0.021) were independent protective factors for postoperative anxiety. As for depression, low literacy (OR = 1.943, P = 0.042), postoperative pain (OR = 2.671, P = 0.001), high clinical stage (OR = 3.469, P = 0.009), and combined liver disease (OR = 4.865, P = 0.000) were independent risk factors for postoperative depression. CD4+/CD8+ (OR = 0.628, P = 0.002) and NK cell ratio (OR = 0.710, P = 0.013) were independent protective factors for postoperative depression. In conclusion, patients with endometrial cancer have a higher incidence of postoperative anxiety and depression where postoperative pain, liver disease, and decreased immune function are risk factors for both anxiety and depression in these patients.

2.
Psychol Med ; : 1-10, 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31839025

RESUMO

BACKGROUND: Affective temperaments have been considered antecedents of major depressive disorder (MDD). However, little is known about how the covariation between alterations in brain activity and distinct affective temperaments work collaboratively to contribute to MDD. Here, we focus on the insular cortex, a critical hub for the integration of subjective feelings, emotions, and motivations, to examine the neural correlates of affective temperaments and their relationship to depressive symptom dimensions. METHODS: Twenty-nine medication-free patients with MDD and 58 healthy controls underwent magnetic resonance imaging scanning and completed the Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS). Patients also received assessments of the Hamilton Depression Rating Scale (HDRS). We used multivariate analyses of partial least squares regression and partial correlation analyses to explore the associations among the insular activity, affective temperaments, and depressive symptom dimensions. RESULTS: A profile (linear combination) of increased fractional amplitude of low-frequency fluctuations (fALFF) of the anterior insular subregions (left dorsal agranular-dysgranular insula and right ventral agranuar insula) was positively associated with an affective-temperament (depressive, irritable, anxious, and less hyperthymic) profile. The covariation between the insula-fALFF profile and the affective-temperament profile was significantly correlated with the sleep disturbance dimension (especially the middle and late insomnia scores) in the medication-free MDD patients. CONCLUSIONS: The resting-state spontaneous activity of the anterior insula and affective temperaments collaboratively contribute to sleep disturbances in medication-free MDD patients. The approach used in this study provides a practical way to explore the relationship of multivariate measures in investigating the etiology of mental disorders.

3.
Medicine (Baltimore) ; 98(46): e17403, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31725603

RESUMO

Studies investigating the association between gene variants and depression susceptibility found inconsistent data. The present study aimed to clarify whether CNR1rs1049353, CNR1 AAT triplet repeat, and CNR2rs2501432 polymorphisms confer higher risk for depressive disorder.Literature from PubMed, Medline, Embase, Scopus, Cochrance Library, and Wanfang databases was searched (up to August 20, 2018). Seven case-control studies with various comorbidities were eligible. We targeted CNR single-nucleotide polymorphisms (SNPs) that have been reported by 2 or more studies to be involved in the current meta-analysis, resulting in a final list of 3 SNPs: CNR1rs1049353, CNR1 AAT triplet repeat polymorphism, and CNR2rs2501432. Odds ratios (ORs) and 95% confidence intervals (CIs) for allele and homozygote comparisons, dominant and recessive models, and triplet repeat polymorphism ((AAT)n≥5, ≥5 vs (AAT)n<5, <5 or <5, ≥5) were assessed using a random effect model as measures of association. Heterogeneity among included studies was analyzed using sensitivity test. Publication bias was also explored by Egger and rank correlation test.overall, no significant association was found between depression and CNR1rs1049353 (G vs A: OR [95% CI] = 1.09 [0.61-1.95]; GG vs AA: 1.29 [0.73-2.26]; GG vs GA+AA: 1.10 [0.57-2.10]; GG+GA vs AA: 1.25 [0.72-2.18]; and AAT triplet repeat polymorphism ((AAT)n≥5, ≥5 vs (AAT)n<5, <5 or <5, ≥5): 1.92 [0.59-6.27]. In contrast, a significant association between CNR2rs2501432 and depression was detected, and the ORs and 95% CIs are as follows: allele contrast (OR = 1.39, 95% CI = [1.12-1.72], P = .003); homozygous (OR = 2.19, 95% CI = [1.34-3.59], P = .002); dominant (OR = 1.93,95% CI = [1.23-3.04], P = .005); and recessive (OR = 1.41, 95% CI = [1.04-1.92], P = .03).This meta-analysis revealed that CNR1rs1049353 or AAT triplet repeat polymorphism had no association with susceptibility to depression, while CNR2rs2501432 polymorphism was a remarkable mark for depression patients.


Assuntos
Depressão/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único , Receptor CB1 de Canabinoide/genética , Receptor CB2 de Canabinoide/genética , Alelos , Estudos de Casos e Controles , Humanos , Razão de Chances , Fatores de Risco
4.
Psychiatry Res Neuroimaging ; 290: 51-57, 2019 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-31288150

RESUMO

Schizophrenia is a severe mental disorder, and the onset of which is preceded by a stage of ultrahigh risk (UHR) for developing psychosis. Therefore, analyzing individuals with UHR is essential for identifying predictive biomarkers for the onset of schizophrenia. The current study aimed to identify such biomarkers based on a voxelwise whole-brain functional degree centrality (FDC) analysis. Conjunction analysis showed that, compared with healthy controls, both UHR subjects and patients with schizophrenia showed significantly increased FDC at the medial prefrontal cortex (MPFC) and significantly decreased FDC at the right fusiform gyrus (FG). The subsequent partial correlation analysis showed significant correlations between the disorganization symptoms and FDCs at the MPFC and the right FG for both UHR subjects and patients with schizophrenia. These findings suggest that FDC within the MPFC and the right FG could be candidate biomarkers for the onset of schizophrenia.

5.
Schizophr Res ; 204: 193-200, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30268820

RESUMO

CACNA1C gene polymorphism rs2007044 has been reported to be associated with schizophrenia, but its underlying brain mechanism is not clear. First, we conducted an exploratory functional magnetic resonance imaging (fMRI) study using an N-BACK task and a Stroop task in 194 subjects (55 schizophrenia patients and 139 healthy controls). Our whole brain analysis found that the risk allele was associated with reduced activation of the left inferior frontal gyrus (IFG) during the Stroop task (cluster size = 390 voxels, P < 0.05 TFCE-FWE corrected; peak MNI coordinates: x = -57, y = -6, z = 30). We also conducted a functional near-infrared spectroscopy (fNIRS) study using the same Stroop task in an independent sample of 126 healthy controls to validate the fMRI finding. Our repeated-measures ANCOVA on the six channels (20, 27, 33, 34, 40 and 46) within the left IFG also found significant result. The polymorphism rs2007044 showed significant effect on the oxy-Hb data (F = 5.072, P = 0.026) and showed significant interaction effect with channels on the deoxy-Hb data (F = 2.841, P = 0.015). Taken together, results of this study suggested that rs2007044 could affect the activation of the left IFG, which was a possible brain mechanism underlying the association between CACNA1C gene polymorphism and schizophrenia.

6.
Neuroimage Clin ; 19: 160-166, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30035013

RESUMO

MIR137 gene has been repeatedly reported as a schizophrenia risk gene in genome-wide association studies (GWAS). A polymorphism (rs1625579) at the MIR137 gene has been associated with both neural activation and behavioral performance during a working memory task. This study examined MIR137's associations with task-related (N-back working memory) fMRI, resting state fMRI, and diffusion tensor images (DTI) data in 177 healthy adults. We found less deactivation of the PCC in risk allele homozygotes (TT) as compared to the GT heterozygotes (cluster size = 630 voxels, cluster level PFWE < 0.001) during the N-back task, which replicated previous findings. Using the identified cluster within the PCC as the seed, we further found decreased functional connectivity between the PCC and the anterior cingulate cortex and its adjacent medial prefrontal cortex (ACC/MPFC) in risk allele homozygotes during both resting state (cluster size = 427 voxels, cluster level PFWE = 0.001) and the N-back task (cluster size = 73 voxels, cluster level PFWE = 0.05). Finally, an analysis of our DTI data showed decreased white matter integrity of the posterior cingulum in risk allele homozygotes (cluster size = 214 voxels, cluster level PFWE = 0.03). Taken together, rs1625579 seems to play an important role in both functional and structural connectivity between the PCC and the ACC/MPFC, which may serve as the brain mechanisms for the link between rs1625579 and schizophrenia.


Assuntos
Predisposição Genética para Doença , Giro do Cíngulo/fisiopatologia , MicroRNAs/genética , Esquizofrenia/genética , Adolescente , Adulto , Imagem de Tensor de Difusão/métodos , Feminino , Estudo de Associação Genômica Ampla/métodos , Humanos , Masculino , Memória de Curto Prazo/fisiologia , Pessoa de Meia-Idade , Vias Neurais/fisiopatologia , Polimorfismo de Nucleotídeo Único/genética , Córtex Pré-Frontal/fisiopatologia , Risco , Esquizofrenia/fisiopatologia , Substância Branca/fisiopatologia , Adulto Jovem
7.
Psychiatry Res Neuroimaging ; 276: 73-79, 2018 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-29628269

RESUMO

The cerebellum plays a crucial role in higher cortical functions through a cerebellar-cerebral circuit. However, the specific mechanisms through which the cerebellum contributes to the neurobiology of schizophrenia remain unclear. Forty-nine first-episode, drug-naive patients with schizophrenia and 50 healthy controls underwent structural and resting-state functional magnetic resonance imaging (rs-fMRI). The MRI data were analyzed using voxel-based morphometry, amplitude of low-frequency fluctuations (ALFF), cerebellum homogeneity (CH), and seed-based functional connectivity (FC). Patients with schizophrenia did not have anatomical and CH alterations in the cerebellum compared with healthy controls. However, they exhibited decreased ALFF in the right Crus I and abnormal cerebellar FC with brain regions within the dorsal attention network, default-mode network, and ventral attention network. The findings indicate that cerebellar abnormalities in first-episode schizophrenia are mainly in the cerebellar-cerebral connectivities, which may contribute to the neurobiology of schizophrenia.


Assuntos
Cerebelo/diagnóstico por imagem , Esquizofrenia/diagnóstico por imagem , Adolescente , Adulto , Atenção , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Mapeamento Encefálico , Estudos de Casos e Controles , Cerebelo/fisiopatologia , Cérebro/diagnóstico por imagem , Cérebro/fisiopatologia , Feminino , Neuroimagem Funcional , Humanos , Imagem por Ressonância Magnética , Masculino , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Descanso , Esquizofrenia/fisiopatologia , Adulto Jovem
8.
Neuroimage Clin ; 17: 1000-1005, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29527501

RESUMO

ZNF804A rs1344706 (A/C) was the first SNP that reached genome-wide significance for schizophrenia. Recent studies have linked rs1344706 to functional connectivity among specific brain regions. However, no study thus far has examined the role of this SNP in the entire functional connectome. In this study, we used degree centrality to test the role of rs1344706 in the whole-brain voxel-wise functional connectome during the resting state. 52 schizophrenia patients and 128 healthy controls were included in the final analysis. In our whole-brain analysis, we found a significant interaction effect of genotype × diagnosis at the precuneus (PCU) (cluster size = 52 voxels, peak voxel MNI coordinates: x = 9, y = - 69, z = 63, F = 32.57, FWE corrected P < 0.001). When we subdivided the degree centrality network according to anatomical distance, the whole-brain analysis also found a significant interaction effect of genotype × diagnosis at the PCU with the same peak in the short-range degree centrality network (cluster size = 72 voxels, F = 37.29, FWE corrected P < 0.001). No significant result was found in the long-range degree centrality network. Our results elucidated the contribution of rs1344706 to functional connectivity within the brain network, and may have important implications for our understanding of this risk gene's role in functional dysconnectivity in schizophrenia.


Assuntos
Encéfalo/patologia , Fatores de Transcrição Kruppel-Like/genética , Vias Neurais/patologia , Polimorfismo de Nucleotídeo Único/genética , Esquizofrenia/genética , Esquizofrenia/patologia , Adulto , Análise de Variância , Encéfalo/diagnóstico por imagem , Conectoma , Feminino , Genótipo , Humanos , Processamento de Imagem Assistida por Computador , Imagem por Ressonância Magnética , Masculino , Vias Neurais/diagnóstico por imagem , Oxigênio/sangue , Escalas de Graduação Psiquiátrica , Esquizofrenia/diagnóstico por imagem , Adulto Jovem
10.
Schizophr Res ; 195: 372-377, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29033280

RESUMO

The dot pattern expectancy (DPX) task has been strongly recommended as a measure of goal maintenance, which is impaired in schizophrenia patients. The current event-related potential (ERP) study was designed mainly to identify the ERP component that could represent the goal maintenance process of the DPX task as indexed by the error rate of the BX vs. AY (EBX-AY). We focused our analysis on the cue-phased contingent negative variation (CNV) and found a significant association between the EBX-AY and the amplitude of the difference wave of cue B vs. cue A (CNVB-A) (for CP3, ß=-0.262, P=0.001; for CPZ, ß=-0.184, P=0.025; for CP4, ß=-0.201, P=0.015). Lower EBX-AY (better goal maintenance) was correlated with larger CNVB-A. Further analysis found a significant association between the error rate of AY condition (EAY) and the amplitude of CNVA (for CP3, ß=-0.180, P=0.029; for CPZ, ß=-0.184, P=0.024; for CP4, ß=-0.208, P=0.011) and a significant association between the error rate of BX condition (EBX) and the amplitude of CNVB-A (for CP3, ß=-0.198, P=0.016; for CPZ, ß=-0.165, P=0.043; for CP4, ß=-0.151, P=0.066), but not the amplitude of the CNVB (all P>0.05). All these results together suggested that the cue-phased CNV could be used to represent the goal maintenance process. Future research needs to verify these results with schizophrenia patients.


Assuntos
Variação Contingente Negativa/fisiologia , Metas , Esquizofrenia/fisiopatologia , Psicologia do Esquizofrênico , Adulto , Análise de Variância , Sinais (Psicologia) , Eletroencefalografia , Feminino , Humanos , Masculino , Tempo de Reação/fisiologia , Estudos Retrospectivos , Adulto Jovem
11.
Med Sci Monit ; 23: 4834-4840, 2017 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-28989170

RESUMO

BACKGROUND The pathogenesis of schizophrenia is complex and oligodendrocyte abnormality is an important component of the pathogenesis found in schizophrenia. This study was designed to evaluate the function of olig2 in cuprizone-induced schizophrenia-like symptoms in a mouse model, and to assess the related mechanisms. MATERIAL AND METHODS The schizophrenia-like symptoms were modeled by administration of cuprizone in mice. Open-field and elevated-plus maze tests were applied to detect behavioral changes. Adenovirus encoding olig2 siRNA was designed to silence olig2 expression. Real-time PCR and western blotting were applied to detect myelin basic protein (MBP), 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), glial fibrillary acidic protein (GFAP) and olig2 expressions. RESULTS Open field test showed that the distance and time spent in the center area were significantly decreased in cuprizone mice (model mice) when compared with control mice (p<0.05). By contrast, olig2 silence could significantly increase the time and distance spent in the center area compared with the model mice (p<0.05). As revealed by elevated-plus maze test, the mice in the model group preferred the open arm and spent more time and distance in the open arm compared with control mice (p<0.05), while olig2 silence significantly reversed the abnormalities (p<0.05). Mechanically, MBP and CNPase expression were reduced in the model group compared with the control (p<0.05). However, olig2 silence reversed the reduction caused by cuprizone modeling (p<0.05). In addition, GFAP was elevated after cuprizone modeling compared with control (p<0.05), and was significantly inhibited by olig2 silence compared with model (p<0.05). CONCLUSIONS Cuprizone-induced schizophrenia-like symptoms involved olig2 upregulation. The silence of olig2 could prevent changes, likely through regulating MBP, CNPase, and GFAP expressions.


Assuntos
Fator de Transcrição 2 de Oligodendrócitos/uso terapêutico , Esquizofrenia/metabolismo , 2',3'-Nucleotídeo Cíclico Fosfodiesterases/análise , 2',3'-Nucleotídeo Cíclico Fosfodiesterases/metabolismo , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Encéfalo/patologia , Cuprizona/administração & dosagem , Modelos Animais de Doenças , Proteína Glial Fibrilar Ácida/análise , Proteína Glial Fibrilar Ácida/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteína Básica da Mielina/análise , Proteína Básica da Mielina/metabolismo , Bainha de Mielina/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Fator de Transcrição 2 de Oligodendrócitos/análise , Fator de Transcrição 2 de Oligodendrócitos/fisiologia , Oligodendroglia/patologia , Oligodendroglia/fisiologia , Esquizofrenia/induzido quimicamente , Regulação para Cima
12.
J Obstet Gynaecol Res ; 42(11): 1445-1450, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27527689

RESUMO

AIM: The clinical application of non-invasive prenatal testing (NIPT) is still very limited in China. We carried out a survey to assess the willingness of Chinese obstetricians to offer NIPT and to determine how they would implement it and what resources they would need for the testing. METHODS: Between June 2014 and June 2015, a survey was conducted at a large academic referral center with data obtained from 392 registered perinatologists and obstetricians who completed an entire questionnaire. RESULTS: Most respondents (72.5%) agreed or strongly agreed that the percentage of women patients refusing to accept NIPT would increase if they were charged directly for the test. Most respondents (82.7%) answered affirmatively that the national health administration agencies should formulate a standard charge for NIPT. The most important factors that influence the application of NIPT are the popularity of the test and its cost. The majority of respondents indicated that there are appropriate reasons for NIPT. CONCLUSION: The importance of NIPT and guidelines for the application of NIPT should be clarified in current clinical practice in China. Extensive education regarding NIPT application is necessary prior to mass implementation.


Assuntos
Atitude do Pessoal de Saúde , Testes Genéticos , Obstetrícia , Perinatologia , Diagnóstico Pré-Natal , Adulto , China , Feminino , Aconselhamento Genético/economia , Testes Genéticos/economia , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Diagnóstico Pré-Natal/economia , Inquéritos e Questionários
13.
Am J Med Genet B Neuropsychiatr Genet ; 171(6): 861-6, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27177275

RESUMO

ANK3 is one of the most promising candidate genes for bipolar disorder (BD). A polymorphism (rs10994336) within the ANK3 gene has been associated with BD in at least three genome-wide association studies of BD [McGuffin et al., 2003; Kieseppä, 2004; Edvardsen et al., 2008]. Because facial affect processing is disrupted in patients with BD, the current study aimed to explore whether the BD risk alleles are associated with the N170, an early event-related potential (ERP) component related to facial affect processing. We collected data from two independent samples of healthy individuals (Ns = 83 and 82, respectively) to test the association between rs10994336 and an early event-related potential (ERP) component (N170) that is sensitive to facial affect processing. Repeated-measures analysis of covariance in both samples consistently revealed significant main effects of rs10994336 genotype (Sample I: F (1, 72) = 7.24, P = 0.009; Sample II: F (1, 69) = 11.81, P = 0.001), but no significant interaction of genotype × electrodes (Ps > 0.05) or genotype × emotional conditions (Ps > 0.05). These results suggested that rs10994336 was linked to early ERP component reflecting facial structural encoding during facial affect processing. These results shed new light on the brain mechanism of this risk SNP and associated disorders such as BD. © 2016 Wiley Periodicals, Inc.


Assuntos
Anquirinas/genética , Anquirinas/fisiologia , Adulto , Afeto/fisiologia , Anquirinas/metabolismo , Transtorno Bipolar/genética , Transtorno Bipolar/metabolismo , Encéfalo , Estudos de Casos e Controles , China , Eletroencefalografia/métodos , Grupos Étnicos/genética , Potenciais Evocados/genética , Face , Reconhecimento Facial , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Fatores de Risco
14.
Biomed Res Int ; 2016: 1765624, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27066497

RESUMO

BACKGROUND: Diverticulum, one of the long-term sequelae of cesarean section, can cause abnormal uterine bleeding and increase the risk of uterine scar rupture. In this study, we aimed to evaluate the efficacy of combined laparoscopic and hysteroscopic repair, a newly occurring method, treating post-cesarean section uterine scar diverticulum. METHODS: Data relating to 40 patients with post-cesarean section uterine diverticulum who underwent combined laparoscopic and hysteroscopic repair were retrospectively analyzed. Preoperative clinical manifestations, size of uterine defects, thickness of the lower uterine segment (LUS), and duration of menstruation were compared with follow-up findings at 1, 3, and 6 months after surgery. RESULTS: The average preoperative length and width of uterine diverticula and thickness of the lower uterine segment were recorded and analyzed. The average durations of menstruations at 1, 3, and 6 months after surgery were significantly shorter than the preoperative one (p < 0.05), respectively. At 6 months after surgery, the overall success improvement rate of surgery was 90% (36/40). Three patients (3/40 = 7.5%) developed partial improvement, and 1/40 (2.5%) was lost to follow-up. CONCLUSIONS: Our findings showed that combined treatment with laparoscopy and hysteroscopy was an effective method for the repair of post-cesarean section uterine diverticulum.


Assuntos
Cesárea/efeitos adversos , Divertículo/cirurgia , Histeroscopia/métodos , Histeroscopia/estatística & dados numéricos , Laparoscopia/métodos , Laparoscopia/estatística & dados numéricos , Doenças Uterinas/cirurgia , Adulto , Feminino , Humanos , Histeroscopia/efeitos adversos , Laparoscopia/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
15.
Hum Brain Mapp ; 37(7): 2398-406, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27004598

RESUMO

Recently, a single nucleotide polymorphism (SNP) in the CAMKK2 gene (rs1063843) was found to be associated with lower expression of the gene in the dorsolateral prefrontal cortex (DLPFC) and with schizophrenia (SCZ) and deficits in working memory and executive function. However, the brain mechanism underlying this association is poorly understood. A functional magnetic resonance imaging (fMRI) study (N = 84 healthy volunteers) involving multiple cognitive tasks, including a Stroop task (to measure attentional executive control), an N-back task (to measure working memory), and a delay discounting task (to measure decision making) to identify the brain regions affected by rs1063843 was performed. Across all three tasks, it was found that carriers of the risk allele consistently exhibited increased activation of the left DLPFC. In addition, the risk allele carriers also exhibited increased activation of the right DLPFC and the left cerebellum during the Stroop task and of the left caudate nucleus during the N-back task. These findings helped to elucidate the role of CAMKK2 in cognitive functions and in the etiology of SCZ. Hum Brain Mapp 37:2398-2406, 2016. © 2016 Wiley Periodicals, Inc.


Assuntos
Atenção/fisiologia , Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina/genética , Desvalorização pelo Atraso/fisiologia , Função Executiva/fisiologia , Memória de Curto Prazo/fisiologia , Córtex Pré-Frontal/fisiologia , Adulto , Mapeamento Encefálico , Núcleo Caudado/diagnóstico por imagem , Núcleo Caudado/fisiologia , Feminino , Predisposição Genética para Doença , Técnicas de Genotipagem , Humanos , Imagem por Ressonância Magnética , Masculino , Testes de Neutralização , Polimorfismo de Nucleotídeo Único , Córtex Pré-Frontal/diagnóstico por imagem , Esquizofrenia/genética
16.
Schizophr Res ; 170(1): 48-54, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26654932

RESUMO

ZNF804A is one of the most promising candidate genes for schizophrenia. Previous fMRI studies have repeatedly shown an association between SNP rs1344706 in this gene and the functional connectivity from the right dorsolateral prefrontal cortex (rDLPFC) to the left hippocampal formation (lHF) during the N-back task. However, the rDLPFC-lHF functional connectivity included several subconnections and it is not known whether rs1344706 plays the same role in these subconnections. This study addressed that question using both fMRI and DTI data of 87 subjects. First, we replicated the association between rs1344706 and the rDLPFC-lHF functional connectivity using our fMRI data from the N-back task. Second, we reconstructed fiber connections between rDLPFC and lHF using our DTI data, which included three subconnections: from lHF to posterior cingulate cortex (PCC), from PCC to anterior cingulated cortex (ACC), and from ACC to rDLPFC. We found that only the lHF-PCC tract showed significantly lower fractional anisotropy (FA) in risk allele homozygotes. Finally, we analyzed the fMRI data (from the N-back task and the resting state). Both consistently showed relatively lower lHF-PCC functional connectivity in risk allele homozygotes. Taken together, the disconnectivity of the lHF-PCC tract seems to be a plausible intermediate phenotype that links rs1344706 and schizophrenia.


Assuntos
Giro do Cíngulo/anatomia & histologia , Giro do Cíngulo/fisiologia , Hipocampo/anatomia & histologia , Hipocampo/fisiologia , Fatores de Transcrição Kruppel-Like/genética , Polimorfismo de Nucleotídeo Único , Adulto , Mapeamento Encefálico , Imagem de Tensor de Difusão , Feminino , Lateralidade Funcional , Técnicas de Genotipagem , Humanos , Imagem por Ressonância Magnética , Masculino , Memória/fisiologia , Vias Neurais/anatomia & histologia , Vias Neurais/fisiologia , Testes Neuropsicológicos , Tempo de Reação , Descanso
17.
Exp Ther Med ; 10(3): 863-868, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26622406

RESUMO

The incidence of depression increases annually but the pathogenesis is not yet fully understood. The aim of the present study was to explore the expression and interaction of tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor (VEGF) in chronic stress-induced depressive rats. A total of 20 adult healthy Sprague Dawley rats (180-220 g) were randomly divided into the control and experimental depression groups. The depression model was established with a chronic stress method, and the success of model construction was assessed through weigh measurements and the sugar consumption and open-field tests. The expression of TNF-α and VEGF was detected using the reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blotting and immunohistochemistry. Compared with the control group, the weight of the rats in the experimental group was found to be reduced (P<0.05). The open-field test showed significant differences in the horizontal and vertical motion of the rats between the two groups, and the rats in the experimental group exhibited a significantly reduced ability to adapt to a new environment (P<0.05). Furthermore, the sensitivity of the rats in the experimental group to reward stimulation was decreased. The relative mRNA expression levels of TNF-α and VEGF in the hippocampus of the experimental group were lower than those in the control group, and western blot analysis revealed that the protein expression of VEGF and TNF-α was reduced in the experimental group. Neurons of the experimental group exhibited reduced immunohistochemical staining compared with neurons from the normal hippocampus in the control group. In conclusion, the present study investigated the association between the occurrence of depression and TNF-α and VEGF at the mRNA and protein levels using RT-qPCR, western blotting, immunohistochemistry and animal behavior experiments. The results provide a fundamental basis for follow-up clinical research.

18.
Schizophr Bull ; 41(1): 57-65, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25170032

RESUMO

Anatomical deficits and resting-state functional connectivity (FC) alterations in prefrontal-thalamic-cerebellar circuit have been implicated in the neurobiology of schizophrenia. However, the effect of structural deficits in schizophrenia on causal connectivity of this circuit remains unclear. This study was conducted to examine the causal connectivity biased by structural deficits in first-episode, drug-naive schizophrenia patients. Structural and resting-state functional magnetic resonance imaging (fMRI) data were obtained from 49 first-episode, drug-naive schizophrenia patients and 50 healthy controls. Data were analyzed by voxel-based morphometry and Granger causality analysis. The causal connectivity of the integrated prefrontal-thalamic (limbic)-cerebellar (sensorimotor) circuit was partly affected by structural deficits in first-episode, drug-naive schizophrenia as follows: (1) unilateral prefrontal-sensorimotor connectivity abnormalities (increased driving effect from the left medial prefrontal cortex [MPFC] to the sensorimotor regions); (2) bilateral limbic-sensorimotor connectivity abnormalities (increased driving effect from the right anterior cingulate cortex [ACC] to the sensorimotor regions and decreased feedback from the sensorimotor regions to the right ACC); and (3) bilateral increased and decreased causal connectivities among the sensorimotor regions. Some correlations between the gray matter volume of the seeds, along with their causal effects and clinical variables (duration of untreated psychosis and symptom severity), were also observed in the patients. The findings indicated the partial effects of structural deficits in first-episode, drug-naive schizophrenia on the prefrontal-thalamic (limbic)-cerebellar (sensorimotor) circuit. Schizophrenia may reinforce the driving connectivities from the left MPFC or right ACC to the sensorimotor regions and may disrupt bilateral causal connectivities among the sensorimotor regions.


Assuntos
Cerebelo/patologia , Giro do Cíngulo/patologia , Vias Neurais/patologia , Córtex Pré-Frontal/patologia , Esquizofrenia/patologia , Tálamo/patologia , Adolescente , Adulto , Encéfalo/patologia , Encéfalo/fisiopatologia , Mapeamento Encefálico , Estudos de Casos e Controles , Causalidade , Cerebelo/fisiopatologia , Feminino , Neuroimagem Funcional , Giro do Cíngulo/fisiopatologia , Humanos , Imagem por Ressonância Magnética , Masculino , Vias Neurais/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Esquizofrenia/fisiopatologia , Tálamo/fisiopatologia , Adulto Jovem
19.
Neuropsychopharmacology ; 40(6): 1383-94, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25490993

RESUMO

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.


Assuntos
Óxido Nítrico Sintase Tipo I/genética , Polimorfismo de Nucleotídeo Único , Córtex Pré-Frontal/fisiopatologia , Esquizofrenia/genética , Esquizofrenia/fisiopatologia , Adulto , Mapeamento Encefálico , Feminino , Lateralidade Funcional , Predisposição Genética para Doença , Genótipo , Técnicas de Genotipagem , Humanos , Imagem por Ressonância Magnética , Masculino , Vias Neurais/fisiopatologia , Testes Neuropsicológicos , Tempo de Reação/genética , Descanso , Esquizofrenia/tratamento farmacológico , Teste de Stroop
20.
Psychiatry Res ; 224(3): 218-24, 2014 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-25242670

RESUMO

The dysconnectivity hypothesis proposes that abnormal resting state connectivity within the default-mode network (DMN) plays a key role in schizophrenia. Little is known, however, about alterations of the network homogeneity (NH) of the DMN in unaffected siblings of patients with schizophrenia. Unaffected siblings have unique advantages as subjects of neuroimaging studies independent of the clinical and treatment issues that complicate studies of the patients themselves. In the present study, we investigated NH of the DMN in unaffected siblings of schizophrenia. Participants comprised 46 unaffected siblings of schizophrenia patients and 50 age-, sex-, and education-matched healthy controls who underwent resting state functional magnetic resonance imaging (fMRI). Automated NH and group independent component analysis (ICA) approaches were used to analyze the data. Compared with healthy controls, the unaffected siblings of schizophrenia patients showed decreased DMN homogeneity in the left precuneus. No significantly increased DMN homogeneity was found in the sibling group relative to the control group. Our results suggest that there is decreased NH of the DMN in unaffected siblings of schizophrenia patients and indicate that the alternative perspective of examining the DMN NH in patients׳ siblings may improve understanding of the nature of schizophrenia.


Assuntos
Mapeamento Encefálico/métodos , Rede Nervosa/fisiopatologia , Lobo Parietal/fisiopatologia , Esquizofrenia/fisiopatologia , Irmãos , Adulto , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Adulto Jovem
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