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BackgroundThe pathogenesis of depression remains not fully understood， and previous studies have suggested that the kynurenine pathway （KP） plays an important role in the pathogenesis of major depressive disorder. ObjectiveTo study the difference in serum KP metabolites level between patients with first-episode and recurrent major depressive disorder， and to testify the correlation between KP metabolites level with the severity of depressive symptoms， so as to provide references for the prevention of recurrence. MethodsA total of 136 patients with major depressive disorder who attended the outpatient clinics of the Affiliated Brain Hospital of Guangzhou Medical University from November 2016 to December 2018 and met the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） diagnostic criteria were included， including 62 patients in the first-episode group and 74 patients in the recurrent group. Meanwhile， 60 healthy subjects were included as control group. All patients were assessed by Hamilton Depression Scale-17 item （HAMD-17）， and serum concentrations of tryptophan （TRP）， kynurenine （KYN） and kynurenic acid （KYNA） were measured by liquid chromatography tandem mass spectrometry （LC-MS/MS）. Then the correlation of HAMD-17 total score and individual item scores with the levels of KP metabolites was tested using partial correlation coefficient. ResultsCompared with the control group， the first-episode group and recurrent group showed a marked decline in TRP concentration （t=-3.044， -4.477， P<0.05 or 0.01） and an increase in KYN/TRP ratio （t=2.343， 3.644， P<0.05 or 0.01）， with significant differences. The KYNA concentrations （t=2.490， 2.636， P<0.05 or 0.01） and KYNA/KYN ratio （t=2.894， 2.616， P<0.01） in first-episode group and control group were notably elevated compared to recurrent group， with statistical difference. Partial correlation analysis in patients with first-episode major depressive disorder demonstrated that KYN/TRP ratio was positively correlated with the HAMD-17 anxiety/somatization factor score （r=0.261， P<0.05）， and KYNA/KYN ratio was negatively correlated with HAMD-17 total score and block factor score （r=-0.286， -0.282， P<0.05）. In patients with recurrent major depressive disorder， KYN/TRP ratio was positively correlated with HAMD-17 anxiety/somatization factor score （r=0.280， P<0.05）. ConclusionKP metabolites in serum differ between first-episode and recurrent major depressive disorder patients， and patients with recurrent episodes experience severe KP metabolite abnormalities. Therefore， KP metabolites are considered to be potential biomarker candidates to assist clinicians in the diagnosis and recurrent prediction of major depressive disorder. ［Funded by National Key Research and Development Program Precision Medicine Research Project （number， 2016YFC0906300）］
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Objective:To explore the effects of early-life maternal deprivation on depressive-like behavior and neurogenesis in the granular layer of hippocampus in adolescent rats (6-7 weeks old).Methods:Neonatal rats were randomly divided into maternal deprivation group and control group, with 3 litters in each group.Rats in the maternal deprivation group were given maternal deprivation from 1 to 14 days after birth and rats in the control group were caged with the mother rats and raised normally.The body weight of rats at 5-6 weeks old was recorded and the increased body weight was calculated.When the rats were 6 weeks old, the sucrose preference test was carried out.Then the rats were killed and immunofluorescence histochemistry was applied to compare the expression of Ki67 and Nestin positive cells in the dentate gyrus of hippocampus.SPSS 22.0 software was used for statistical analysis.The data of the two groups were tested to conform to the normal distribution, and then t-test was carried out. Results:There was significant difference in body weight growth between the two groups at the age of 5-6 weeks.Compared with the control group, rats in the maternal deprivation group had lower body weight growth ((20.57±2.19) g, (30.57±1.25) g, t=3.96, P<0.01)) and lower sucrose preference rate((58.38±53.14)%, (73.88±3.67)%, t=3.21, P<0.01). The results of immunofluorescence showed that the number of Ki67 positive cells in the granular layer of hippocampus in the maternal deprivation group was less than that in the control group ((5.13±0.31), (7.60±0.38), t=5.09, P<0.01), and the number of Nestin immunofluorescence positive cells was more than that in the control group ((16.65±0.79), (7.64±0.70), t=8.51, P<0.01). The Nestin immunofluorescence positive cells in the maternal deprivation group had more protrusions and branches, and the morphology was similar to astrocytes, while the immunofluorescence positive cells in the control group had fewer protrusions, and the cell body was oval. Conclusions:Early-life maternal deprivation leads to depressive-like behavior in adolescent rats, which may be associated with the decrease of neurogenesis and activation of astrocytes in the dentate gyrus of the hippocampus.
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ObjectiveTo explore the mental health status and relevant factors among community residents during the normalization stage of prevention and control of COVID-19. MethodsFrom August 28 to September 7， 2020， an online cross-sectional survey using snowball sampling was conducted among community residents via Wenjuanxing platform， and their mental health status were assessed using Patients' Health Questionnaire Depression Scale-9 item（PHQ-9）， Generalized Anxiety Disorder-7 item（GAD-7）， Insomnia Severity Index（ISI） and Chinese Perceived Stress Scale（CPSS）. ResultsAmong the 476 community residents， the detection rates of depression， anxiety， insomnia and high perceived stress were 32.35%， 21.22%， 24.58% and 48.74%， respectively. In terms of gender， the detection rate of high perceived stress was higher in male than in female（χ2=5.269）； in terms of marital status， the detection rates of depression and anxiety among the unmarried， divorced or widowed residents was higher than those of the married residents（χ2=5.251， 8.851）； in terms of mental health service status， the detection rates of depression， anxiety， insomnia and high perceived stress among residents with mental health service needs was higher than those among residents without the needs（χ2=46.316， 66.934， 20.153， 21.576）， with statistical significance（P<0.05 or 0.01）. Correlation analysis showed that the age of community residents was negatively correlated with CPSS score（r=-0.171， P<0.01）， sleep duration was negatively correlated with PHQ-9， GAD-7 and ISI scores（r=-0.210， -0.247， -0.297， P<0.01）， and time spent following news on COVID-19 per day was negatively correlated with ISI score（r=-0.097， P<0.05）. ConclusionDuring the normalization stage of prevention and control of COVID-19， the majority of community residents experience the symptoms of depression， anxiety， insomnia and high perceived stress. Male and younger residents are more likely to experience high levels of perceived stress. Those with shorter sleep duration and needs for mental health services are more likely to experience symptoms of depression， anxiety and insomnia， and those with short time spent following news on COVID-19 are more likely to experience insomnia symptom.
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Cognitive impairment is one of the three primary symptoms of schizophrenic patients and shows important value in early detection and warning for high-risk individuals. To study the specifics of electroencephalogram (EEG) in patients with schizophrenia under the cognitive load, we collected EEG signals from 17 schizophrenic patients and 19 healthy controls, extracted signals of each band based on wavelet transform, calculated the characteristics of nonlinear dynamic and functional brain networks, and automatically classified the two groups of people by using a machine learning algorithm. Experimental results indicated that the correlation dimension and sample entropy showed significant differences in α, β, θ, and γ rhythm of the Fp1 and Fp2 electrodes between groups under the cognitive load. These results implied that the functional disruptions in the frontal lobe might be the important factors of cognitive impairments in schizophrenic patients. Further results of the automatic classification analysis indicated that the combination of nonlinear dynamics and functional brain network properties as the input characteristics of the classifier showed the best performance, with the accuracy of 76.77%, sensitivity of 72.09%, and specificity of 80.36%. The results of this study demonstrated that the combination of nonlinear dynamics and function brain network properties may be potential biomarkers for early screening and auxiliary diagnosis of schizophrenia.
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Objective To investigate the predictive value of serum adiponectin (APN) for post-stroke depression (PSD) in patients with ischemic stroke. Methods Patients with acute ischemic stroke admitted to the Departments of Neurology, the Affiliated Brain Hospital of Guangzhou Medical University, and Dongguan Changping Hospital were enrolled prospectively from September 2016 to January 2018. Serum APN levels were measured by radioimmunoassay the next day after admission. PSD was diagnosed by using the Diagnostic and Statistical Manual of Mental Disorders (4th Edition) at one month after discharge. The baseline clinical features in the PSD group and the non-PSD group were compared. Multivariable logistic regression analysis was used to determine the risk factors for PSD. The receiver operating characteristic (ROC) curve was used to analyze the predictive value of APN for PSD. Results A total of 220 patients were enrolled, including 57 (25.9%) in the PSD group and 163 (74.1%) in the non-PSD group. The proportion of patients with diabetes (P=0.020) and living alone (P=0.012), as well as age (P=0.17), homocysteine (P=0.009), C-reactive protein ( P=0.001), and National Institutes of Health Stroke Scale score ( P=0.007) in the PSD group were significantly higher than those in the non-PSD group, while the APN level was significantly lower than that in the non-PSD group (P=0.003). Multivariate logistic regression analysis showed that the 4th quartile of serum APN level was used as a reference, the 1st quartile of APN level was an independent risk factor for PSD (odds ratio, 4 .202, 95% confidence interval 1.401-12.067; P=0.013). ROC curve analysis showed that the area under the curve of serum APN level for predicting PSD was 0.642 (95% confidence interval 0.564-0.721; P=0.001). The optimal cutoff value was 6.4 mg/L, and its sensitivity of predicting PSD was 63.2%, the specificity was 63.8%, the positive predictive value was 83.3%, and the negative predictive value was 57 .7%. Conclusion Serum APN has a certain predictive value for PSD in patients with ischemic stroke.
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Objective To conduct an in-depth analysis on the correlation of miRNA and Alzheimer disease (AD) pathogenesis and provide an experimental basis for AD potential biomarkers by analysis of serum miRNA expression profiles in AD patients. Methods The miRNA expression profiles were exmined in 7 severe AD patients and 5 normal controls using high-throughput sequencing and bioinformatic analysis. Results Compared with the normal controls, there were serum differential expression of 112 miRNAs (DEmiRNAs) including 57 being up-regulated and 55 being down-regulated in patients with severe AD (P<0.05). GO-term function enrichment analysis showed that DEmiRNAs participated in the protein binding, ion binding, transcription metal binding, and biological metabolism and regulation process of organelle and cell membrane, etc. KEGG pathway enrichment analysis found that PI3K-Akt signal pathway was an important pathway of target genes. Conclusion The differential expression of serum miRNAs may be potential biomarkers of AD and the target genes of DEmiRNAs are related to the pathological changes of AD.
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Objective To investigate the effects of ketamine and propofol on cardiovascular system and cognitive function in the patients with depression during the modified electroconvulsive therapy (MECT). Methods A total of 60 patients with depression treated by MECT were randomly divided into 2 groups. Induced anesthesia with ketamine and propofol were performed respectively during MECT. The course of treatment was 8 times. The mean arterial pressure(MAP)was recorded before therapy and at 5 min after MECT.Depression and the cognitive function were evaluated by using the Hamilton Depression Scale(HAMD)and the Wisconsin Card Sorting Test(WCST)before treatment and 1 day after treatment. Results There was no significant difference in MAP between the two groups after MECT(P > 0.05). The HAMD scores of the two groups were lower than those before treatment(P 0.05). But in completing classification of WCST ,the ketamine group was better than the propofol group(P<0.05). Conclusion Propofol has no obvious influence on the cognition function and little influence on MAP,so it could be the first choice of anaesthetic for the induction of MECT.
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Objective To explore the effects of integrated treatment model (psychosocial interventions combined with drug therapy) in schizophrenia and analyze the influence of medication attitude on treatment compliance and psychiatric symptoms in different intervention models.Methods A total of 170 patients with schizophrenia were enrolled from 2012 to 2015.Patients were randomly divided into two groups:the integrated treatment group (86 patients) with drug therapy and psychosocial intervention,and the conventional drug treatment group (84 patients) with only drug intervention.Dug attitude inventory (DAI),self-awareness inventor (SAI),positive and negative symptoms scale (PANSS) were used to assess medication attitude,treatment compliance and clinical psychotic symptoms for all patients in the following 3 months,6 months and 12 months.Results Compared with medication-alone group,the integrated treatment group achieved significant improvement in psychiatric symptoms,including positive symptom and general psychopathology as well as significant reduction in scores in DAI and SAI (P＜0.05).In the conventional drug treatment group,the PANSS score was positively correlated with the increased score of DAI (β=0.31,P=0.02),which was mediated by the improvement in treatment adherence (β=0.18,P=0.18).There was no significant correlation between PANSS score and the increase score of DAI in the integrated treatment group(P=0.62).However,the increased score of SAI was positively correlated with the positive symptom of PANSS scale (r=0.31,P=0.01) and with the general psychiatric symptom scale (r=0.36,P＜0.01).Conclusion This study demonstrates that medication attitude can improve the treatment of mental symptoms by increasing compliance in the medication-only group.Symptom improvement is associated with improved compliance but not with medication attitudes in the integrated treatment model.
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Objective To investigate regional spontaneous brain activity in mild cognition impairment (MCI) patients with amnesic (aMCI) and non-amnesic (naMCI).Methods Twenty-five aMCI patients,21 naMCI patients and 15 normal controls (NC) underwent resting-state functional magnetic resonance imaging.The regional homogeneity (ReHo) map of the whole brain was obtained by calculating the similarity of each voxel with its nearest 26 voxel time series.The differences of ReHo map across the whole brain among three groups were compared.Results In aMCI group,ReHo values were lower in right frontal lobe and higher in left middle temporal gyrus and left cerebellum compared with NC (P＜0.05,Alphasim correction).In naMCI group,ReHo values were higher in anterior cingulate cortex and right middle frontal gyrus and lower in right parahippocampa gyrus,right middle temporal gyrus as well as right precuneus compared with NC (P＜0.05,Alphasim correction).Compared with naMCI,the ReHo values were significantly higher in left prefrontal gyrus,left middle temporal gyrus and lower in right cerebellum (P＜0.05,Alphasim correction).Conclusion There are differences in spontaneous brain activity of left prefrontal gyrus,left middle temporal gyrus and right cerebellum between aMCI and naMCI,which may be used to differentiate brain function between aMCI and naMCI patients.
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Objective In order to evaluate that whether Pluronic P85 coated poly(butylcyanoacrylate) nanoparti-cles was able to deliver antiepileptic drug phenytoin into the brain va bypassing mesial temporal lobe epilepsy (MTLE)-induced Pgp in a rat model of MTLE. Methods The rat model of MTLE, induced by li-pilocarpine, was divided in-to two groups (6 for nanoparticle drug group and 7 for PHT drug group). Immunohistochemistry assay was performed to detect Pgp expression at the hippocampus. Nanoparticles were prepared by interfacial polymerization method. Dialysate samples of brain were collected at 30, 60, 120, 180, 240 and 300 min after drug administration by microdialysis tech-nology. Samples were analyzed by high performance liquid chromatography (HPLC). Results The area under the curve (AUC) ratio of brain/plasma in Nanoparticle drug group was 0.370.10 which was significantly higher compared with 0.190.06 in conventional PHT drug group (P<0.05). The Pgp immunopositive area, as assessed by analysis of labeled surface area, was higher in the DG, CA3 and CA1 sector in the hippocampus of MTLE rats when compared to the normal rats. Conclusions Pluronic P85 coated PBCA nanoparticles can significantly deliver PHT into brain via bypassing MTLE-induced Pgp in a rat model of MTLE.
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Objective To investigate the cognitive characteristics and vascular risk factor between early onset de?pression and late onset depression in late life depression and provide a clue to elucidate the cause of cognitive impairment in late life depression. Method Fifty-six late life depression patients were recruited in our hospital, including 29 early on?set depression patients and 27 late onset depression patients. 25 controls were recruited from Guangzhou community. Cog?nitive evaluation were conducted in all the patients and controls, including MMSE, memory, attention, language, visuospa?tial abilities,executive function and Framingham vascular risk assessment, and analyze the cognitive and vascular risk be?tween the patients. Result There were statistically significant differences in overall cognitive assessment MMSE(24.8 ± 2.9,22.8±3.5,P=0.030), symbol digit modalities test(SDMT)(29.8±10.5, 22.9±11.8, P=0.028), clock drawing test(CDT) (3.6 ± 0.8, 2.9 ± 1.3, P=0.006) and trail making test(TMT) (60.4 ± 20.6, 74.7 ± 28.8, P=0.027) between late onset depression and early onset depression. In addition, the score of vascular risk assessment was significant between late onset depression and early onset depression(14.6±2.7,12.3±2.2,P=0.001). Conclusion Compare with early onset depression, late onset de?pression has much severe cognitive impairments and increased vascular risk factors.
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Objective To explore the plasma levels of soluble CD40 (sCD40) and soluble CD40 ligand (sCD40L) in the patients with Alzheimer’s disease (AD) and those with amnestic mild cognitive impairment (aMCI). Methods The levels of plasma sCD40 and sCD40L were measured in 20 patients with AD, 35 patients with aMCI, and 32 cognitively normal controls (NC) using commercially available ELISAs. The cognitive function of AD and aMCI patients was mea?sured by mini-mental state examination (MMSE). Results There were significant differences in plasma sCD40 among AD, aMCI and NC groups (P<0.05) as the medians (the upper and lower quartiles) of plasma levels were 123.3 (97.4, 149.5) pg/mL, 102.9 (63.6, 124.0) pg/mL and 70.66 (51.0, 90.8) pg/mL, respectively. There were significant differences in plasma sCD40L among AD, aMCI and NC groups (P<0.05) as plasma levels were 537.0 (316.0, 1134.0) pg/mL, 316.0 (190.0,546.0) pg/mL and 167.0 (107.5,478.0) pg/mL. A negative correlation between the plasma concentrations of sCD40L and the MMSE scores was found in aMCI patients (r=-0.736, P<0.001). Conclusions There are relevant chang?es of plasma sCD40 and sCD40L levels in patients with AD and aMCI. The present results suggest that plasma levels of sCD40 and sCD40L may be appropriate biomarkers for AD patients and indicate that CD40-CD40L signaling may be in?volved in AD pathophysiology.
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Objective We aimed to use 1H-MRS to characterize metabolite concentrations in the bilateral hippo?campus in GPI patient. Methods Metabolite ratios in the bilateral hippocampus were compared between patients with GPI (n=52) and Normal Control (NC) (n=38). Clinical neurological tests were measured in all subjects and were correlat?ed to the metabolite concentrations. Results The GPI patients showed significantly lower concentrations of N-acetylas?partate(NAA)/creatine(Cr) ratios in the bilateral hippocampus region compared to the NC subjects. There was significant?ly difference in the NAA/Cr ratios between the mild GPI dementia and the severe GPI dementia groups on the left hippo?campus region. We found that the NAA/Cr ratios concentrations were positively correlated with Mini Mental state Exami?nation (MMSE) and Montreal Cognitive Assessment scale (MoCA) scores in the left hippocampus region and the mI/Cr ra?tios concentrations were positively correlated. Conclusions GPI Patients have neuronal dysfunction in the bilateral hippo?campus. The severity of cognitive impairments is associated with the severity of the damage in the left side.
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Objective To investigate the sleep architecture in dementia with Lewy bodies (DLB),and study the sleep architecture and cognitive functions in DLB.Methods We described polysomnography (PSG) findings in 34 consecutive subjects diagnosed with DLB.All the patients underwent Mini-Mental State Examination (MMSE),Montreal Cognitive Assessment (MoCA),Clinical Dementia Rating (CDR) to quantify cognitive functions.Results (1)Sleep architecture analysis:DLB group compared to normal control group,the sleep period time (SPT) was reduced (P ＜ 0.05),total sleep time (TST) and sleep efficiency (SE) were decreased,total wake time (TWT) and wake after sleep onset (WASO) were increased,1 non-rapid eye movement (NREM) sleep (TS1),2NREM sleep (TS2),total NREM sleep (TNREMS),and REM sleep (TREMS) time were significantly decreased (P ＜0.01).(2)The DLB patients were divided into groups based on MMSE,MoCA,qnd CDR scores,the sleep architecture of each group was no significant difference (P ＞ 0.05).Conclusions Patients with DLB exists sleep architecture disorder.The cognitive functions and sleep architecture changes in patients with DLB have no obvious correlation.It is different from other degenerative dementia.
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Objective To study the interaction of BDNF gene C270T polymorphism and estrogen receptor alpha (ERα)gene Xba Ⅰ loci and Pvu Ⅱ loci polymorphism in late-onset Alzheimer's disease(LOAD)pathogenesis in southern Chinese Han population.Methods BNDF gene C270T locus,ERα gene Xba Ⅰ site and Pvu Ⅱ site polymorphisms were examined in 203 LOAD patients and normal controls using PCR-RFLP technique.Results There was an interaction be-tween BDNF gene and ERα gene,and BDNF gene C270T locus CC genotype and the ERa gene Xba Ⅰ locus xx genotype increased the LOAD incidance risk(OR=2.38,95%CI:1.02～5.53).Conclusions BDNF gene and ERα gene are in-teracted each other in the pathogenesis of LOAD.Patients carrying both BDNF gene C270T locus CC genotype and the ERα gene Xba Ⅰ locus xx genotypes might have an increased risk for LOAD.