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1.
Cereb Cortex ; 33(7): 3683-3700, 2023 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-36005854

RESUMO

Difficulties in parsing the multiaspect heterogeneity of schizophrenia (SCZ) based on current nosology highlight the need to subtype SCZ using objective biomarkers. Here, utilizing a large-scale multisite SCZ dataset, we identified and validated 2 neuroanatomical subtypes with individual-level abnormal patterns of the tensor-based morphometric measurement. Remarkably, compared with subtype 1, which showed moderate deficits of some subcortical nuclei and an enlarged striatum and cerebellum, subtype 2, which showed cerebellar atrophy and more severe subcortical nuclei atrophy, had a higher subscale score of negative symptoms, which is considered to be a core aspect of SCZ and is associated with functional outcome. Moreover, with the neuroimaging-clinic association analysis, we explored the detailed relationship between the heterogeneity of clinical symptoms and the heterogeneous abnormal neuroanatomical patterns with respect to the 2 subtypes. And the neuroimaging-transcription association analysis highlighted several potential heterogeneous biological factors that may underlie the subtypes. Our work provided an effective framework for investigating the heterogeneity of SCZ from multilevel aspects and may provide new insights for precision psychiatry.


Assuntos
Imageamento por Ressonância Magnética , Esquizofrenia , Humanos , Imageamento por Ressonância Magnética/métodos , Esquizofrenia/diagnóstico por imagem , Neuroimagem , Cerebelo/diagnóstico por imagem , Atrofia
2.
Environ Res ; 258: 119406, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38871277

RESUMO

To carry out the diagnosis and evaluation of the ecosystem health in Yuxi three-lake watershed, this paper presents the changing trend of its health state, and predicts the future development. This also provides ideas for maintaining the regional ecosystem health, and then gradually improves the ecological environment quality. Taking Fuxian Lake, Qilu Lake and Xingyun Lake (the three-lake watershed) in Yuxi City, Yunnan Province, Southwest China as the research object, a model combining pressure-state-response and kernel density estimation (PSR-KDE) adopts to diagnose and evaluate the ecosystem health of the "three lake" watershed from 2010 to 2020, and the distribution map of ecosystem health index has obtained by the evaluation indexes integration based on GIS spatial analysis. Hence, the evaluation results have visualized on the map. The results show that: The distribution of ecosystem health index in the study area was 0.1530-0.7045 in 2010, 0.2056-0.7512 in 2015, and 0.2248-0.7662 in 2020. 0.12% was in the pathological area in 2010. After 2015, the pathological condition of ecosystem health has completely solved, and the proportion of unhealthy ecosystems was 11.95% in 2010, 7.38% in 2015, and 5.97% in 2020. The ecosystem health index of the study region was 0.5523 in 2010, 0.5807 in 2015, and 0.5815 in 2020, it indicates that the ecosystem was in a sub-health state. From 2010 to 2020, the ecosystem health around Qilu Lake was the most worrying, followed by the northwest of Fuxian Lake and the northern and southern regions of Xingyun Lake. The ecosystem health of the three-lake watershed showed significant improvement from 2010 to 2020. The study ecosystem health assessment and early warning in the three-lake watershed is significant to the ecological environment protection and management of the plateau lake basin, the restoration of the territorial space ecology and the economic development of the surrounding area.

3.
BMC Med ; 21(1): 263, 2023 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-37468932

RESUMO

BACKGROUND: It remains a challenge to predict the long-term response to antipsychotics in patients with schizophrenia who do not respond at an early stage. This study aimed to investigate the optimal predictive cut-off value for early non-response that would better predict later non-response to antipsychotics in patients with schizophrenia. METHODS: This multicenter, 8-week, open-label, randomized trial was conducted at 19 psychiatric centers throughout China. All enrolled participants were assigned to olanzapine, risperidone, amisulpride, or aripiprazole monotherapy for 8 weeks. The positive and negative syndrome scale (PANSS) was evaluated at baseline, week 2, week 4, and week 8. The main outcome was the prediction of nonresponse. Nonresponse is defined as a < 20% reduction in the total scores of PANSS from baseline to endpoint. Severity ratings of mild, moderate, and severe illness corresponded to baseline PANSS total scores of 58, 75, and 95, respectively. RESULTS: At week 2, a reduction of < 5% in the PANSS total score showed the highest total accuracy in the severe and mild schizophrenia patients (total accuracy, 75.0% and 80.8%, respectively), and patients who were treated with the risperidone and amisulpride groups (total accuracy, 82.4%, and 78.2%, respectively). A 10% decrease exhibited the best overall accuracy in the moderate schizophrenia patients (total accuracy, 84.0%), olanzapine (total accuracy, 79.2%), and aripiprazole group (total accuracy, 77.4%). At week 4, the best predictive cut-off value was < 20%, regardless of the antipsychotic or severity of illness (total accuracy ranging from 89.8 to 92.1%). CONCLUSIONS: Symptom reduction at week 2 has acceptable discrimination in predicting later non-response to antipsychotics in schizophrenia, and a more accurate predictive cut-off value should be determined according to the medication regimen and baseline illness severity. The response to treatment during the next 2 weeks after week 2 could be further assessed to determine whether there is a need to change antipsychotic medication during the first four weeks. TRIAL REGISTRATION: This study was registered on Clinicaltrials.gov (NCT03451734).


Assuntos
Antipsicóticos , Esquizofrenia , Humanos , Antipsicóticos/uso terapêutico , Esquizofrenia/tratamento farmacológico , Olanzapina/uso terapêutico , Risperidona/uso terapêutico , Aripiprazol/uso terapêutico , Amissulprida/uso terapêutico , Resultado do Tratamento
4.
Mol Psychiatry ; 27(2): 1205-1216, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34728799

RESUMO

Evidence suggests that complex interactions between the immune system and brain have important etiological and therapeutic implications in schizophrenia. However, the detailed cellular and molecular basis of immune dysfunction in schizophrenia remains poorly characterized. To better understand the immune changes and molecular pathways, we systemically compared the cytokine responses of peripheral blood mononuclear cells (PBMCs) derived from patients with schizophrenia and controls against bacterial, fungal, and purified microbial ligands, and identified aberrant cytokine response patterns to various pathogens, as well as reduced cytokine production after stimulation with muramyl dipeptide (MDP) in schizophrenia. Subsequently, we performed single-cell RNA sequencing on unstimulated and stimulated PBMCs from patients and controls and revealed widespread suppression of antiviral and inflammatory programs as well as impaired chemokine/cytokine-receptor interaction networks in various immune cell subpopulations of schizophrenic patients after MDP stimulation. Moreover, serum MDP levels were elevated in these patients and correlated with the course of the disease, suggesting increased bacterial translocation along with disease progression. In vitro assays revealed that MDP pretreatment altered the functional response of normal PBMCs to its re-stimulation, which partially recapitulated the impaired immune function in schizophrenia. In conclusion, we delineated the molecular and cellular landscape of impaired immune function in schizophrenia, and proposed a mutual interplay between innate immune impairment, reduced pathogen clearance, increased MDP translocation along schizophrenia development, and blunted innate immune response. These findings provide new insights into the pathogenic mechanisms that drive systemic immune activation, neuroinflammation, and brain abnormalities in schizophrenia.


Assuntos
Citocinas , Esquizofrenia , Acetilmuramil-Alanil-Isoglutamina/metabolismo , Acetilmuramil-Alanil-Isoglutamina/farmacologia , Bactérias/metabolismo , Citocinas/metabolismo , Fungos/metabolismo , Humanos , Leucócitos Mononucleares/metabolismo , Esquizofrenia/metabolismo
5.
Br J Psychiatry ; 221(6): 732-739, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35144702

RESUMO

BACKGROUND: Previous analyses of grey and white matter volumes have reported that schizophrenia is associated with structural changes. Deep learning is a data-driven approach that can capture highly compact hierarchical non-linear relationships among high-dimensional features, and therefore can facilitate the development of clinical tools for making a more accurate and earlier diagnosis of schizophrenia. AIMS: To identify consistent grey matter abnormalities in patients with schizophrenia, 662 people with schizophrenia and 613 healthy controls were recruited from eight centres across China, and the data from these independent sites were used to validate deep-learning classifiers. METHOD: We used a prospective image-based meta-analysis of whole-brain voxel-based morphometry. We also automatically differentiated patients with schizophrenia from healthy controls using combined grey matter, white matter and cerebrospinal fluid volumetric features, incorporated a deep neural network approach on an individual basis, and tested the generalisability of the classification models using independent validation sites. RESULTS: We found that statistically reliable schizophrenia-related grey matter abnormalities primarily occurred in regions that included the superior temporal gyrus extending to the temporal pole, insular cortex, orbital and middle frontal cortices, middle cingulum and thalamus. Evaluated using leave-one-site-out cross-validation, the performance of the classification of schizophrenia achieved by our findings from eight independent research sites were: accuracy, 77.19-85.74%; sensitivity, 75.31-89.29% and area under the receiver operating characteristic curve, 0.797-0.909. CONCLUSIONS: These results suggest that, by using deep-learning techniques, multidimensional neuroanatomical changes in schizophrenia are capable of robustly discriminating patients with schizophrenia from healthy controls, findings which could facilitate clinical diagnosis and treatment in schizophrenia.


Assuntos
Esquizofrenia , Humanos , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/tratamento farmacológico , Estudos Prospectivos , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Substância Cinzenta/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Redes Neurais de Computação
6.
Mol Psychiatry ; 25(11): 2905-2918, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-31391545

RESUMO

Accumulating evidence suggests that gut microbiota plays a role in the pathogenesis of schizophrenia via the microbiota-gut-brain axis. This study sought to investigate whether transplantation of fecal microbiota from drug-free patients with schizophrenia into specific pathogen-free mice could cause schizophrenia-like behavioral abnormalities. The results revealed that transplantation of fecal microbiota from schizophrenic patients into antibiotic-treated mice caused behavioral abnormalities such as psychomotor hyperactivity, impaired learning and memory in the recipient animals. These mice also showed elevation of the kynurenine-kynurenic acid pathway of tryptophan degradation in both periphery and brain, as well as increased basal extracellular dopamine in prefrontal cortex and 5-hydroxytryptamine in hippocampus, compared with their counterparts receiving feces from healthy controls. Furthermore, colonic luminal filtrates from the mice transplanted with patients' fecal microbiota increased both kynurenic acid synthesis and kynurenine aminotransferase II activity in cultured hepatocytes and forebrain cortical slices. Sixty species of donor-derived bacteria showed significant difference between the mice colonized with the patients' and the controls' fecal microbiota, highlighting 78 differentially enriched functional modules including tryptophan biosynthesis function. In conclusion, our study suggests that the abnormalities in the composition of gut microbiota contribute to the pathogenesis of schizophrenia partially through the manipulation of tryptophan-kynurenine metabolism.


Assuntos
Transplante de Microbiota Fecal , Microbioma Gastrointestinal , Cinurenina/metabolismo , Esquizofrenia/metabolismo , Esquizofrenia/microbiologia , Psicologia do Esquizofrênico , Animais , Estudos de Casos e Controles , Dopamina/metabolismo , Humanos , Ácido Cinurênico/metabolismo , Masculino , Camundongos , Serotonina/metabolismo , Triptofano/metabolismo
7.
Ann Hum Genet ; 84(4): 331-338, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32162681

RESUMO

The present study aimed to perform chromosome examination and pedigree analysis on three patients with semen abnormality who had undergone in vitro fertilization-embryo transfer (IVF-ET). Peripheral blood cell culture and chromosome karyotyping were performed on 4,200 individuals who had undergone chromosome examination. Among them, 155 pregnant women who had successfully conceived were subjected to amniotic cell culture and chromosome karyotyping and those with abnormal chromosome karyotype were further subjected to C-banding and whole-genome sequencing. Mosaicism for a 46,X,inv(Y)(p11.2q11.2)pat/45,X karyotype was identified in the probands and immediate adult male relatives. The incidence of this mosaicism in the study population was only 0.07% (3/4,200), which is reported for the first time. For the proband of pedigree A, the results of whole-genome sequencing and other tests were normal, and the chromosome karyotype of IVF fetuses was 46,X,inv(Y)(p11.2q11.2)pat. All the male members of three pedigrees have normal phenotypes, with no features of Turner's syndrome (45,X) or hermaphroditism (45,X/46,XY), suggesting that the inverted Y chromosome is extremely unstable and particularly susceptible to loss in somatic cells. So we speculate this karyotype may be a unique type of inverted Y chromosome in somatic cells.


Assuntos
Cromossomos Humanos X/genética , Cromossomos Humanos Y/genética , Mosaicismo , Adulto , Povo Asiático/genética , China , Feminino , Humanos , Cariotipagem , Masculino , Linhagem , Gravidez
8.
Br J Psychiatry ; 216(5): 267-274, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31169117

RESUMO

BACKGROUND: Schizophrenia is a complex mental disorder with high heritability and polygenic inheritance. Multimodal neuroimaging studies have also indicated that abnormalities of brain structure and function are a plausible neurobiological characterisation of schizophrenia. However, the polygenic effects of schizophrenia on these imaging endophenotypes have not yet been fully elucidated. AIMS: To investigate the effects of polygenic risk for schizophrenia on the brain grey matter volume and functional connectivity, which are disrupted in schizophrenia. METHOD: Genomic and neuroimaging data from a large sample of Han Chinese patients with schizophrenia (N = 509) and healthy controls (N = 502) were included in this study. We examined grey matter volume and functional connectivity via structural and functional magnetic resonance imaging, respectively. Using the data from a recent meta-analysis of a genome-wide association study that comprised a large number of Chinese people, we calculated a polygenic risk score (PGRS) for each participant. RESULTS: The imaging genetic analysis revealed that the individual PGRS showed a significantly negative correlation with the hippocampal grey matter volume and hippocampus-medial prefrontal cortex functional connectivity, both of which were lower in the people with schizophrenia than in the controls. We also found that the observed neuroimaging measures showed weak but similar changes in unaffected first-degree relatives of patients with schizophrenia. CONCLUSIONS: These findings suggested that genetically influenced brain grey matter volume and functional connectivity may provide important clues for understanding the pathological mechanisms of schizophrenia and for the early diagnosis of schizophrenia.


Assuntos
Substância Cinzenta/patologia , Hipocampo/patologia , Hipocampo/fisiopatologia , Herança Multifatorial , Córtex Pré-Frontal/fisiopatologia , Esquizofrenia/genética , Esquizofrenia/patologia , Adolescente , Adulto , Feminino , Estudo de Associação Genômica Ampla , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esquizofrenia/diagnóstico , Adulto Jovem
9.
Radiology ; 283(3): 810-819, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28045645

RESUMO

Purpose To investigate auditory verbal hallucination (AVH)-specific patterns of brain activity within the resting-state networks (RSNs) that have been proposed to underpin the neural mechanisms of schizophrenia (SZ). Materials and Methods This cross-sectional study was approved by the local ethics committee, and written informed consent was obtained from all participants prospectively recruited. Independent component analysis was used to investigate RSNs in 17 patients with first-episode untreated SZ with AVHs, 15 patients with SZ without AVHs, and 19 healthy control subjects who underwent resting-state functional magnetic resonance imaging. Dual regression was implemented to perform between-group analysis. Regional brain function was then explored within RSNs by using the amplitude of low-frequency fluctuation. Two-sample t tests were used to compare regional brain function between the two patient groups, and Pearson correlation analysis was used to characterize the relationship between imaging findings and severity of AVHs. Receiver operating characteristic analysis was used to evaluate the diagnostic performance of these brain function measures. Results Independent component analysis demonstrated symptom-specific abnormal disrupted coactivation within the auditory, default mode, executive, motor, and frontoparietal networks and was pronounced in the auditory cortex, supramarginal gyrus, insula, putamen, dorsolateral prefrontal cortex, angular gyrus, precuneus, and thalamus (P < .05 with false discovery rate correction). Amplitude of low-frequency fluctuation analysis demonstrated similar patterns within these RSNs (P < .05 with false discovery rate correction). Furthermore, a positive correlation between the degree of coactivation within the motor network and the severity of AVHs was observed in patients with SZ with AVHs (r = 0.67, P = .003). The area under the receiver operating characteristic curve was 0.76-0.90 for all RSNs. Conclusion These findings indicate that dysfunctional brain regions are involved in auditory processing, language production and monitoring, and sensory information filtering in patients with SZ with AVHs, which may be helpful in furthering the understanding of pathophysiological correlates of AVHs in SZ. Online supplemental material is available for this article.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Alucinações/diagnóstico por imagem , Imageamento por Ressonância Magnética , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/fisiopatologia , Alucinações/etiologia , Humanos , Imageamento por Ressonância Magnética/métodos , Descanso , Esquizofrenia/complicações
10.
Int J Neuropsychopharmacol ; 19(2)2015 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-26232790

RESUMO

BACKGROUND: White matter disturbances and myelin impairment are key features of schizophrenia. The antipsychotic drug quetiapine can promote the maturation of oligodendrocytes, but the molecular mechanisms remain largely unknown. METHODS: The schizophrenia-like behaviors, degrees of demyelination, and levels of Notch signaling molecules in forebrains of adult male C57BL/6 mice were examined after fed with cuprizone (0.2% wt/wt) in the presence or absence of 10mg/kg/d quetiapine for 6 weeks. These parameters were also observed after the transcranial injection of Notch signaling inhibitor MW167 (1mM) daily during the last week of the treatment period. RESULTS: Quetiapine ameliorated the schizophrenia-like behaviors and decreased expression of myelin basic protein and inhibition of Notch signaling molecules, such as Notch1, Hes1, and Hes5, in the forebrain that induced by cuprizone. These beneficial effects of quetiapine were abolished by MW167. CONCLUSIONS: The antipsychotic and myelin protective effects of quetiapine are mediated by Notch signaling in a mouse model of cuprizone-induced demyelination associated with schizophrenia-like behaviors. The Notch pathway might therefore be a novel target for the development of antipsychotic drugs.


Assuntos
Cuprizona/toxicidade , Doenças Desmielinizantes/metabolismo , Fumarato de Quetiapina/administração & dosagem , Receptores Notch/metabolismo , Esquizofrenia/tratamento farmacológico , Esquizofrenia/metabolismo , Animais , Doenças Desmielinizantes/patologia , Doenças Desmielinizantes/prevenção & controle , Injeções Intraventriculares , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Bainha de Mielina/efeitos dos fármacos , Bainha de Mielina/metabolismo , Bainha de Mielina/patologia , Fármacos Neuroprotetores/administração & dosagem , Peptídeos/farmacologia , Receptores Notch/antagonistas & inibidores , Esquizofrenia/patologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia
11.
Plants (Basel) ; 13(6)2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38592957

RESUMO

The mining of metal minerals generates considerable mining wasteland areas, which are characterized by poor soil properties that hinder plant growth. In this study, a field plot experiment was carried out in the mining wasteland of the Lanping lead-zinc mine in Yunnan Province to study the effects of applying three organic materials-biochar (B), organic fertilizer (OF), and sludge (S)-at concentrations of 1% (mass fraction), on promoting the soil of mining wasteland and the growth of two plant varieties (Huolieniao and Yingshanhong). The results showed that the amount of available nutrients in the surface soil of a mining wasteland could be considerably increased by S and OF compared to the control check (CK). In the rhizosphere soils of two Rhododendron simsii varieties, the application of S increased the available phosphorus (P) content by 66.4% to 108.8% and the alkali-hydrolyzed nitrogen (N) content by 61.7% to 295.5%. However, the contents of available cadmium (Cd) and available lead (Pb) were reduced by 17.1% to 32.0% and 14.8% to 19.0%, respectively. Moreover, three organic materials increased the photosynthetic rate and biomass of two R. simsii varieties. Specifically, OF and S were found to significantly increase the biomass of R. simsii. Organic materials have direct impacts on the increased plant height and biomass of R. simsii. Additionally, organic materials indirectly contribute to the growth of R. simsii by reducing the content of available Cd and available Pb in rhizosphere soil while increasing the content of available nutrients according to the structural equation model (SEM). Overall, S can stabilize Cd and Pb, increase soil nutrient contents, and promote the growth of R. simsii effectively, and has great potential in the vegetation reconstruction of mining wasteland.

12.
Heliyon ; 10(11): e32085, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38868034

RESUMO

(1) Studying the dynamic correlation between land use and the eco-environment in the Dianchi Basin is important for improving the basin's spatial layout and enhancing ecological development and conservation; (2) Through dynamic analysis and comprehensive evaluation of land use, the introduction of ecological and environmental quality index, and the use of FLUS models, the impacts on eco-environments in the Dianchi Basin for the recent 20 years were analyzed; (3) The past two decades witnessed a constant increase in the construction land in the Dianchi Basin and a decline in the farmland at an average annual rate of 0.93 %; The utilization level of land in the Dianchi Basin presented a negative correlation with the quality of the area's eco-environment, which reduces first and then increases; When natural production becomes a priority, both the construction land and farmland have witnessed growth. However, when ecological protection becomes a priority, it is projected that by 2035, the Dianchi Basin will achieve its highest eco-environmental quality index; (4) Studying how the change of land use types affects eco-environment is crucial for optimizing the current allocation of land resources and promoting sustainable development in the basin.

13.
J Affect Disord ; 356: 72-79, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38588727

RESUMO

IMPORTANCE: The global increase in urbanization has coincided with a rise in depression prevalence. However, the effect of urbanization on depression remains controversial, especially for the elderly. OBJECTIVE: To clarify how urbanization impacts depression in the elderly from a network perspective. DESIGN, SETTING, AND PARTICIPANTS: This sectional cohort study used data from China Health and Retirement Longitudinal Study (CHARLS). MAIN OUTCOMES AND MEASURES: The occurrence of depressive symptoms in urban and rural elderly residents. Network metrics of depressive symptoms. RESULTS: Of the 13,993 participants, lower incidence of depressive symptoms was observed in urban (26.3 %, 95 % CI, 24.7 %-27.8 %) than in rural (40.4 %, 95 % CI, 39.5 %-41.3 %, P < 0.0001) residents. However, higher incidence of depressive symptoms was observed in urban (26.3 %, 95 % CI, 25.2 %-28.4 %) than in rural (17.5 %, 95 % CI, 16.1 %-18.9 %, P < 0.0001) residents in a subset of 2898 pairs of participants after PSM. No difference in the network structure and metrics between urban and rural residents before (M = 0.071, p = 0.054, S = 0.037, p = 0.80) and after (M = 0.085, p = 0.133, S = 0.086, p = 0.47) PSM was detected. The networks structure revealed that negative affect was strongly connected to somatic symptoms and that the two anhedonic symptoms were also strongly connected. CONCLUSIONS: The current study indicated the homogeneity of the ultimate nature of depression between rural and urban residents from the network perspective, supporting the viewpoint that urbanization might not impose influence on depression. Further researches delving deeper into the complexity of the issue may provide new insights into our understanding of depression in an urban environment among the elderly.


Assuntos
Depressão , População Rural , População Urbana , Urbanização , Humanos , Idoso , Feminino , Masculino , China/epidemiologia , População Rural/estatística & dados numéricos , Depressão/epidemiologia , População Urbana/estatística & dados numéricos , Estudos Longitudinais , Pessoa de Meia-Idade , Incidência , Estudos Transversais , Idoso de 80 Anos ou mais , Prevalência
14.
Adv Sci (Weinh) ; : e2400929, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38900070

RESUMO

To elucidate the brain-wide information interactions that vary and contribute to individual differences in schizophrenia (SCZ), an information-resolved method is employed to construct individual synergistic and redundant interaction matrices based on regional pairwise BOLD time-series from 538 SCZ and 540 normal controls (NC). This analysis reveals a stable pattern of regionally-specific synergy dysfunction in SCZ. Furthermore, a hierarchical Bayesian model is applied to deconstruct the patterns of whole-brain synergy dysfunction into three latent factors that explain symptom heterogeneity in SCZ. Factor 1 exhibits a significant positive correlation with Positive and Negative Syndrome Scale (PANSS) positive scores, while factor 3 demonstrates significant negative correlations with PANSS negative and general scores. By integrating the neuroimaging data with normative gene expression information, this study identifies that each of these three factors corresponded to a subset of the SCZ risk gene set. Finally, by combining data from NeuroSynth and open molecular imaging sources, along with a spatially heterogeneous mean-field model, this study delineates three SCZ synergy factors corresponding to distinct symptom profiles and implicating unique cognitive, neurodynamic, and neurobiological mechanisms.

15.
Schizophr Bull ; 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38754993

RESUMO

BACKGROUND AND HYPOTHESIS: Schizophrenia (SZ) is a prevalent mental disorder that imposes significant health burdens. Diagnostic accuracy remains challenging due to clinical subjectivity. To address this issue, we explore magnetic resonance imaging (MRI) as a tool to enhance SZ diagnosis and provide objective references and biomarkers. Using deep learning with graph convolution, we represent MRI data as graphs, aligning with brain structure, and improving feature extraction, and classification. Integration of multiple modalities is expected to enhance classification. STUDY DESIGN: Our study enrolled 683 SZ patients and 606 healthy controls from 7 hospitals, collecting structural MRI and functional MRI data. Both data types were represented as graphs, processed by 2 graph attention networks, and fused for classification. Grad-CAM with graph convolution ensured interpretability, and partial least squares analyzed gene expression in brain regions. STUDY RESULTS: Our method excelled in the classification task, achieving 83.32% accuracy, 83.41% sensitivity, and 83.20% specificity in 10-fold cross-validation, surpassing traditional methods. And our multimodal approach outperformed unimodal methods. Grad-CAM identified potential brain biomarkers consistent with gene analysis and prior research. CONCLUSIONS: Our study demonstrates the effectiveness of deep learning with graph attention networks, surpassing previous SZ diagnostic methods. Multimodal MRI's superiority over unimodal MRI confirms our initial hypothesis. Identifying potential brain biomarkers alongside gene biomarkers holds promise for advancing objective SZ diagnosis and research in SZ.

16.
Mol Cell Biochem ; 375(1-2): 105-13, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23291919

RESUMO

Paroxetine is a widely used antidepressant in clinic. Besides its role in inhibition of serotonin reuptake, resent studies indicate that the increase of hippocampal neurogenesis is also involved in its pharmacology. However, only limited data are available in this regard and its effect on the hippocampus-derived neural stem cell (NSCs) has not been well elucidated. In present study, we utilized hippocampus-derived NSCs from fetal rats to investigate the direct effect of paroxetine on the neurogenesis of NSCs and explore the possible cellular and molecular mechanisms. The results showed that paroxetine not only promoted the proliferation of NSCs, but also promoted NSCs to differentiate into neurons other than glial cells. In addition, the elevated protein levels of phosphorylated ERK1/2, Bcl-2, and brain-derived neurotrophic factor were also observed after paroxetine was administered. Furthermore, the proliferative effect and promotion of NSCs differentiating predominantly into neurons of paroxetine was inhibited by U0126, an ERK1/2 phosphorylation inhibitor. In conclusion, these data indicate that paroxetine can promote neurogenesis of neural stem cells, and this effect might be mediated by ERK1/2 signal pathways.


Assuntos
Antidepressivos de Segunda Geração/farmacologia , Hipocampo/citologia , Células-Tronco Neurais/fisiologia , Neurogênese/efeitos dos fármacos , Paroxetina/farmacologia , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Butadienos/farmacologia , Proliferação de Células , Células Cultivadas , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feto/citologia , Proteína Glial Fibrilar Ácida/metabolismo , Sistema de Sinalização das MAP Quinases , Células-Tronco Neurais/efeitos dos fármacos , Nitrilas/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Esferoides Celulares/efeitos dos fármacos , Esferoides Celulares/fisiologia , Tubulina (Proteína)/metabolismo , Regulação para Cima
17.
Depress Anxiety ; 29(1): 4-9, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22065498

RESUMO

BACKGROUND: Although the diagnosis of melancholia has had a long history, the validity of the current DSM-IV definition remains contentious. We report here the first detailed comparison of melancholic and nonmelancholic major depression (MD) in a Chinese population examining in particular whether these two forms of MD differ quantitatively or qualitatively. METHODS: DSM-IV criteria for melancholia were applied to 1,970 Han Chinese women with recurrent MD recruited from 53 provincial mental health centers and psychiatric departments of general medical hospitals in 41 cities. Statistical analyses, utilizing Student's t-tests and Pearson's χ(2) , were calculated using SPSS 13.0. RESULTS: Melancholic patients with MD were distinguished from nonmelancholic by being older, having a later age at onset, more episodes of illness and meeting more A criteria. They also had higher levels of neuroticism and rates of lifetime generalized anxiety disorder, panic disorder, and social and agoraphobia. They had significantly lower rates of childhood sexual abuse but did not differ on other stressful life events or rates of MD in their families. DISCUSSION: Consistent with most prior findings in European and US populations, we find that melancholia is a more clinically severe syndrome than nonmelancholic depression with higher rates of comorbidity. The evidence that it is a more "biological" or qualitatively distinct syndrome, however, is mixed.


Assuntos
Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo/epidemiologia , Adulto , Fatores Etários , Idade de Início , Criança , Comparação Transcultural , Transtorno Depressivo/diagnóstico , Transtorno Depressivo Maior/classificação , Transtorno Depressivo Maior/diagnóstico , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva , Síndrome
18.
Depress Anxiety ; 29(1): 10-5, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22065525

RESUMO

BACKGROUND: A number of clinical features potentially reflect an individual's familial vulnerability to major depression (MD), including early age at onset, recurrence, impairment, episode duration, and the number and pattern of depressive symptoms. However, these results are drawn from studies that have exclusively examined individuals from a European ethnic background. We investigated which clinical features of depressive illness index familial vulnerability in Han Chinese females with MD. METHODS: We used lifetime MD and associated clinical features assessed at personal interview in 1,970 Han Chinese women with DSM-IV MD between 30-60 years of age. Odds Ratios were calculated by logistic regression. RESULTS: Individuals with a high familial risk for MD are characterized by severe episodes of MD without known precipitants (such as stress life events) and are less likely to feel irritable/angry or anxious/nervous. CONCLUSIONS: The association between family history of MD and the lack of a precipitating stressor, traditionally a characteristic of endogenous or biological depression, may reflect the association seen in other samples between recurrent MD and a positive family history. The symptomatic associations we have seen may reflect a familial predisposition to other dimensions of psychopathology, such as externalizing disorders or anxiety states.


Assuntos
Transtorno Depressivo Maior/epidemiologia , Predisposição Genética para Doença/epidemiologia , Adulto , China/epidemiologia , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/psicologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Acontecimentos que Mudam a Vida , Pessoa de Meia-Idade , Razão de Chances , Escalas de Graduação Psiquiátrica , Risco , Índice de Gravidade de Doença
19.
Brain Imaging Behav ; 16(5): 2110-2119, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35732912

RESUMO

White matter tracts alterations have been reported in schizophrenia (SZ), but whether such abnormalities are associated with the effects of the disorder itself and/or genetic vulnerability remains unclear. Moreover, the specific patterns of different parts of these altered tracts have been less well studied. Thus, diffusion-weighted images were acquired from 38 healthy controls (HCs), 48 schizophrenia patients, and 33 unaffected first-degree relatives of SZs (FDRs). Diffusion properties of the 25 major tracts automatically extracted with probabilistic tractography were calculated and compared among groups. Regarding the peripheral regions of the tracts, significantly higher diffusivity values in the left superior longitudinal fasciculus (SLF) and the left anterior thalamic radiation (ATR) were observed in SZs than in HCs and unaffected FDRs. However, there were no significant differences between HCs and FDRs in these two tracts. While no main effects of group with respect to the core regions of the 25 tracts survived multiple comparisons correction, FDRs had significantly higher diffusivity values in the left medial lemniscus and lower diffusivity values in the middle cerebellar peduncle than HCs and SZs. These findings enhance the understanding of the abnormal patterns in the peripheral and core regions of the tracts in SZs and those at high genetic risk for schizophrenia. Our results suggest that alterations in the peripheral regions of the left SLF and ATR are features of established illness rather than genetic predisposition, which may serve as critical neural substrates for the psychopathology of schizophrenia.


Assuntos
Leucoaraiose , Esquizofrenia , Substância Branca , Humanos , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/genética , Esquizofrenia/complicações , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Imageamento por Ressonância Magnética , Imagem de Difusão por Ressonância Magnética , Rede Nervosa/patologia , Leucoaraiose/patologia
20.
World J Clin Cases ; 10(34): 12543-12550, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36579088

RESUMO

BACKGROUND: As shown in the statistics from the World Health Organization, it is estimated that approximately 75000 new cases of cervical cancer occur every year in China. In 2008, 33000 people died of cervical cancer in China. It is proven that most women are at risk of cervical cancer. The progression from human papillomavirus (HPV) infection to cervical cancer can be several years or decades, which offers a unique opportunity to prevent cancer. AIM: To observe the changes in ThinPrep cytology tests (TCT) and HPV infection in patients who were detected to be positive via TCT screening of cervical cancer and further explore the biopsy results. METHODS: This paper performed a follow-up study on 206 cervical cancer screening-positive patients of 12231 total cases from our previous research. We conducted an observational study on the TCT results based on the interpretation of The Bethesda System. RESULTS: Over a 5-year period, 10 cases received consistent follow-up. The proportions of cases in which glandular epithelial lesions were detected increased over the follow-up period. The differences between the years were statistically significant (P < 0.01). Over the 5 years, the proportion of patients whose squamous epithelial lesions transformed into glandular epithelial lesions increased yearly. Annual positive rates of HPV infection were: year 1, 73% (24/33); year 2, 43% (6/14); year 3, 36% (9/25); year 4, 50% (9/18); and year 5, 25% (6/24). The positive detection rate after biopsy over a 9-year period was 29%. CONCLUSION: The follow-up study for 5 years to 9 years revealed a tendency to change from squamous epithelial lesions to glandular epithelial lesions and an improvement of the disease (which had not been reported previously). The HPV test indicated a high negative conversion ratio of the viral infection. However, the follow-up cases were not found to have persistent infection of high-risk HPV. Therefore, early intervention of cervical cancer screening is necessary. Low re-examination compliance, patient education, and preventive measures should be enhanced.

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