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1.
J Affect Disord ; 268: 55-60, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32158007

RESUMO

BACKGROUND: Sex differences between psychotic depression (PD) and non-psychotic depression (NPD) have received little systematic study. This study was conducted to investigate sex difference in patients with psychotic and non-psychotic major depressive disorder in a Chinese Han population. METHODS: In this cross-sectional study, a total of 1718 first-episode and drug-naïve outpatients with major depressive disorder were recruited. Demographic and clinical characteristics were collected. All subjects were rated on the Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA) and the Positive and Negative Syndrome Scale (PANSS). RESULTS: The prevalence of PD in female patients (10.97%) was higher than that in male patients (7.99%). Analysis of variance (ANOVA) showed that female patients were older compared with male patients in NPD group, but there were no significant differences in demographic and clinical variables between female and male PD patients. Further, there were no sex differences in the scores of HAMD, HAMA and positive symptom subscale of PANSS in both PD and NPD groups. Two-way ANOVA showed that PD patients had significantly higher scores on the HAMD, HAMA and positive symptom subscale of PANSS than non-PD patients. However, there were no significant effects of sex and sex* subtypes. LIMITATIONS: The main limitations are cross-sectional design and inability to control selection bias. CONCLUSIONS: Our findings show significant differences in clinical profiles between PD and NPD patients; however, no sex difference has been observed in the either PD or NPD patients.

2.
Schizophr Bull ; 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32185388

RESUMO

Accumulating studies have shown that high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) may improve cognitive dysfunction of the patients with schizophrenia (SCZ), but with inconsistent results. The present study aims to assess the efficacy of different frequencies of neuronavigated rTMS in ameliorating cognitive impairments and alleviating the psychotic symptoms. A total of 120 patients were randomly assigned to 3 groups: 20 Hz rTMS (n = 40), 10 Hz rTMS (n = 40), or sham stimulation (n = 40) for 8 weeks, and then followed up at week 32. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was performed to assess the cognitive functions of the patients at baseline, at the end of week 8, and week 32 follow-up. Psychotic symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS) at baseline and at the end of week 2, week 4, week 6, week 8, and week 32 follow-up. Our results demonstrated that 20 Hz rTMS treatment produced an effective therapeutic benefit on immediate memory of patients with chronic SCZ at week 8, but not in the 10 Hz group. Interestingly, both 10 Hz and 20 Hz rTMS treatments produced delayed effects on cognitive functions at the 6-month follow-up. Moreover, in both 10 Hz rTMS and 20 Hz rTMS, the improvements in RBANS total score were positively correlated with the reduction of PANSS positive subscore at the 6-month follow-up. Stepwise regression analysis identified that the visuospatial/constructional index, immediate memory index, and prolactin at baseline were predictors for the improvement of cognitive impairments in the patients. Our results suggest that add-on HF rTMS could be an effective treatment for cognitive impairments in patients with chronic SCZ, with a delayed effect. Trial registration: clinicaltrials.gov identifier-NCT03774927.

3.
Transl Psychiatry ; 10(1): 79, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32098946

RESUMO

Cognitive impairment is a central aspect of schizophrenia (SCZ) that occurs at the onset of the disease and is related to poor social function and outcome in patients with SCZ. Recent literatures have revealed repetitive transcranial magnetic stimulation (rTMS) to be one of the efficient medical interventions for cognitive impairments. However, no study has been conducted to investigate the treatment effectiveness of 20 Hz rTMS with neuronavigation system administered to the left dorsolateral prefrontal cortex (DLPFC) in patients with schizophrenia. In this randomized, double-blind and sham-controlled study, 56 patients were enrolled in 20 Hz rTMS (n = 28) or sham stimulation (n = 28) over left DLPFC for 8 weeks. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was performed to measure the cognitive function at baseline and after 8 weeks of rTMS treatment. The positive and negative syndrome scales (PANSS) was performed to assess the clinical symptoms at baseline, after 2-week treatment, 4-week treatment, 6-week treatment, and 8-week treatment. Totally, 15 subjects (seven in active group and eight in sham group) dropped out during the trial and the main findings were from completed 41 patients. At 2 weeks, 4 weeks, and 6 weeks, there were no significant differences in PANSS total score and subscores between the sham and treatment groups. At 8 weeks, the 20 Hz rTMS significantly increased the immediate memory score compared with the sham. Furthermore, the improvement in the immediate memory score was correlated with the decrease in the excitement factor score of the patients with SCZ. Our results suggest that 20 Hz rTMS appears to be an effective treatment for improving the cognitive performance and reducing the clinical symptoms of patients with SCZ.

4.
Transl Psychiatry ; 10(1): 62, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32066712

RESUMO

There is evidence that obesity or higher body mass index is correlated with cognitive impairment in schizophrenia. Recent studies have demonstrated that genetic risk factors, such as the NRG3, are correlated with both elevated BMI and reduced cognitive function. In present study, we aimed to determine whether possession of the NRG3 rs10748842 influences the correlation between elevated BMI and reduced cognitive ability in schizophrenia. To our knowledge, this has never been examined before. A total of 625 inpatients with schizophrenia and 400 controls were recruited. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was performed to assess cognitive function. We used multiple analysis of covariance (MANCOVA), analyses of covariance (ANCOVA), Pearson correlations, partial correlations, and multivariate regression analysis to test the influence of NRG3 rs10748842 on the aforementioned variables. All RBANS five sub-scores and total score were lower in patients than those in controls (all p < 0.001). Patients carrying NRG3 rs10748842 TC + CC heterozygous genotype had lower attention score compared to TT homozygous genotype (adjusted F = 4.77, p = 0.029). BMI was positively associated with language score in patients (ß = 0.387, t = 2.59, p = 0.01). Interestingly, we further found positive association between BMI and language score in TT carriers (partial correlations: r = 0.13, adjusted p = 0.004; multivariate regression: ß = 0.42, t = 2.66, p = 0.008), but not in CT + CC carrier (p > 0.05). Our study demonstrated that NRG3 rs10748842 was associated with cognitive impairments, especially attention performance in schizophrenia. Moreover, NRG3 rs10748842 altered the effect of BMI on cognitive impairments as measured by the RBANS language score in chronic patients with schizophrenia.

5.
Transl Psychiatry ; 10(1): 18, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-32066717

RESUMO

Accumulating studies have revealed gender differences in many aspects of schizophrenia (SZ), including obesity and cognitive function. The relationship between obesity and cognitive impairment in SZ has been studied before; however, the results are inconsistent. This study was designed to examine the sex differences in the relationship between body mass index (BMI) and cognitive deficits in Chinese patients with chronic SZ, which have not been investigated yet. 176 chronic patients with SZ (male/female = 108/68) and 200 controls (male/female = 120/80) were enrolled to compare the sex differences in cognitive functions measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), BMI, and their associations. The clinical symptoms were evaluated using the positive and negative syndrome scales (PANSS). Our results showed that male patients had lower BMI and more negative symptoms but fewer positive symptoms than female patients (all p < 0.05). However, there was no significant sex difference in RBANS scores. In male patients, BMI was correlated with age of onset, PANSS general psychopathology, total score, negative symptom, together with RBANS language, visuospatial/construction, and attention. Further regression analysis showed that in male patients, BMI was significantly associated with RBANS language, PANSS general psychopathology, PANSS total score, and age of onset, with adjusted R2 = 0.22. These findings revealed significant sex differences in BMI, cognitive dysfunctions and their association in SZ. Nonetheless, these results should only be considered as preliminary because of the cross-sectional design, which will deserve further replication in first-episode patients using a prospective longitudinal design.

6.
Hum Psychopharmacol ; 35(2): e2724, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32052509

RESUMO

OBJECTIVE: Sex differences in bipolar disorder are well recognized but little attention has been paid to sex differences in homocysteine or hyperhomocysteinemia in bipolar patients. This study compared gender differences in homocysteine levels and rates of hyperhomocysteinemia in Chinese inpatients with bipolar disorder. METHODS: A total of 198 BD patients and 84 healthy controls were enrolled. The Young Mania Rating Scale, Hamilton Depression Rating Scale, and the Clinical Global Impressions-Severity scale were used to assess the affective symptomatology. Fasting plasma Hcy levels were measured by high-performance liquid chromatography. RESULTS: Men had higher homocysteine levels than women and the prevalence of hyperhomocysteinemia in male patients was approximately twice that in female patients. Logistic regression analyses showed that HHcy was associated with less frequent use of valproate in males and being overweight in females. Further correlation analysis and multivariate regression analysis demonstrated that Hcy levels were inversely correlated with valproate treatment in men and positively associated with overweight in women. CONCLUSIONS: In bipolar patients, there are significant differences between sexes in the levels of homocysteine and prevalence of hyperhomocysteinemia. This appears to be associated with lower prevalence of valproate prescribing in men and with being overweight in women.

7.
J Affect Disord ; 266: 671-677, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32056943

RESUMO

BACKGROUND: Some studies have shown that long-term exposure to job stress could result in burnout, and BDNF polymorphism may play an important role in its psychopathological mechanism. However, the inter-relationships between the job-related stress, serum BDNF level, BDNF genotype and job burnout have not been examined. This study was to explore the job stress × BDNF rs2049046 interaction and the role of serum BDNF level in job burnout in a Chinese Han population. METHODS: Using a cross-sectional design, 205 healthy subjects were recruited from a public institution in Beijing and assessed for job stress using the House and Rizzo's Work Stress Scale, and job burnout using the Maslach Burnout Inventory (MBI). The BDNF rs2049046 polymorphism was genotyped and serum BDNF (sBDNF) levels were assayed in all of subjects. RESULTS: The correlations between the job stress score and two burnout subscale scores (emotional exhaustion and cynicism) were significant (both p < 0.001), but not with professional efficacy. There were no significant main effects of the BDNF rs2049046 genotype on burnout, and no significant correlation was observed between sBDNF levels and job burnout. However, the interaction between the job stress and the BDNF rs2049046 genotype (F = 2.709, df = 2, 183, p = 0.032) or between the job stress and sBDNF levels on burnout was significant (t = -2.132, p = 0.035). To be specific, the individuals with the BDNF rs2049046 AT genotype showed a greater susceptibility to the burnout cynicism compared to AA homozygote only in medium-stress group (F = 4.327, df = 1,117, p = 0.015). The individuals who had lower sBDNF showed higher burnout level than those who had higher sBDNF in low-stress group. CONCLUSIONS: Our findings suggest that the BDNF system may interact with job stress to affect burnout, showing that interaction between BDNF rs2049046 and job stress or the interaction between BDNF levels with work stress on certain burnout dimensions.

8.
Vet Immunol Immunopathol ; 221: 110009, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31945652

RESUMO

A 14-day experiment was conducted to explore the pathological process and immune response of soybean meal (SBM) induced enteritis (SBMIE) in grass carp (Ctenopharyngodon idellus). The complete replacement of dietary fish meal (FM) with SBM resulted in a remarkable reduction in final body weight, weight gain ratio, and feed conversion efficiency (p < 0.05). The typical histopathological changes of SBMIE appeared starting at day 4, and progressively increased in severity until day 8, then gradually subsided after day 11. The course of SBMIE could be divided into incubation period (days 1-2), prodromal period (days 3-6), symptomatic period (days 7-10), and convalescent period (days 11-14). Transcription levels of pro-inflammatory cytokines, including IL-1ß, TNF-α, IL-6, IL-8, IL-17A/F1 and IFN-γ2, were up-regulated during the prodromal period, and then down-regulated during the convalescent period. Transcript levels of anti-inflammatory cytokines (IL-10 and TGFß1) and their receptors (IL-10R1 and TßRII), were up-regulated during the prodromal and convalescent periods. Transcript levels of MHCIIß, Igµ, Igτ, TCRδ, TCRß, CD4, and CD8α were altered in SBMIE. Furthermore, expression levels of T-bet, IFN-γ2, RORγ2 and IL-17A/F1 were significantly increased in the initiation of enteritis, whereas the transcript levels of Foxp3 and IL-2/15Ra were significantly up-regulated in the repair of enteritis. In conclusion, grass carp SBMIE is regulated by the adjustment of SBM-based diet intake, and the changes of the above-mentioned genes expression suggest that these genes may be involved in SBMIE.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31931089

RESUMO

OBJECTIVES: Previous studies have shown that cognitive impairment plays a key role in suicide, an important factor leading to premature death in schizophrenia (SCZ) patients. Empathy has received extensive attention recently; however, the relationship of empathy with suicide in schizophrenia is still unknown. The main aim of this study was to investigate the prevalence of suicide attempts and its association with empathy and other characteristics in Chinese chronic SCZ patients. METHODS: The suicide attempt data, together with demographic characteristics and clinical variables were collected from 627 chronic inpatients with schizophrenia. We utilized the Positive and Negative Syndrome Scale (PANSS) for the psychopathological symptoms, and the Interpersonal Reactivity Index (IRI) for affective and cognitive empathy in this study. RESULTS: We found a suicide attempt rate of 11.3% in chronic SCZ patients. Compared to non-attempters, suicide attempters were more likely to be women, had younger age and higher education levels, as well as higher positive symptoms and depressive factor score, but lower negative symptoms of PANSS (all p < .05). Moreover, after controlling the confounding factors, suicide attempters scored higher in Personal Distress subscale of IRI (F1, 455 = 5.446, p = .020) than non-attempters. CONCLUSIONS: The prevalence of suicide attempt is high in chronic SCZ patients. Its risk factors include some demographic and clinical variables. Moreover, suicide attempters experienced stronger personal distress, suggesting that stronger empathy may be a risk factor of suicide.

10.
Clin Neurophysiol ; 131(3): 725-733, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32000073

RESUMO

OBJECTIVE: Cognitive deficits are core symptoms of schizophrenia; however, their pathophysiological mechanisms are still unclear. A sensory gating deficit, as reflected by P50 suppression, has been repeatedly shown in schizophrenia patients, which may be associated with cognitive deficits in this disorder. The present study was to examine the relationship between the P50 suppression and cognitive deficits in patients with schizophrenia, which is still under-investigated. METHOD: We recruited 38 chronic schizophrenia patients and 32 matched healthy controls, and assessed their cognition with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and P50 suppression with the electroencephalography system. RESULTS: The total and its 4 index scores (all p < 0.05) except for the visuospatial/ constructional index of RBANS were significantly lower in patients compared with healthy controls. However, only the language and attention passed Bonferroni corrections. Patients displayed a significantly higher P50 ratio, higher S2 amplitude, and lower S1 amplitude (all p < 0.05) than healthy controls. Interestingly, only in the patients, the S1 amplitude was associated with both language and attention, and the S2 amplitude with both visuospatial/ constructional and language (all p < 0.05), although all of these significances did not pass the Bonferroni corrections. The P50 ratio was not associated with any of the RBANS scores (all p > 0.05). CONCLUSIONS: Our results suggest the P50 suppression deficits in Chinese patients with schizophrenia, which may be associated with cognitive impairments of this illness. Moreover, the amplitude of S1 and the amplitude of S2 may be involved in the different cognitive domain deficits in schizophrenia patients. SIGNIFICANCE: This study suggests that the P50 components may possibly be effective biomarkers for cognitive deficits in patients with schizophrenia.

11.
Dev Comp Immunol ; 106: 103613, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31935401

RESUMO

Teleost fish are the most primitive bony vertebrates that contain B cells; thus, comparative analysis of teleost naïve/mature B cells and plasma cells can provide helpful evidence for understanding the evolution paradigms of these two B-cell subpopulations in vertebrates. In this study, we developed monoclonal antibody against grass carp IgM and identified two different IgM+ cell subsets: IgM+ lymphocytes (Lym), resembling naïve/mature B cells, and IgM+ myeloid cells (Mye), resembling plasma cells. Like plasma cells in mammals, the size of IgM+ Mye is significantly larger than that of IgM+ Lym, as revealed by flow cytometric analysis and transmission electron microscopy. The IgM+ Mye were further verified as plasma cells because they showed gene expression patterns similar with those of human plasma cells and a great capacity to secrete IgM. Like mammalian IgM+ and IgA+ plasma cells, not IgG+ plasma cells, grass carp IgM+ Mye also expressed membrane immunoglobulins, a feature conserved in IgM+ plasma cells in vertebrates. Furthermore, recombinant CD40L or IL-21 alone could induce the plasma cell generation and IgM secretion, while the combination of CD40L and IL-21 had greater effect on IgM secretion, but not on plasma cell generation. This study fills an important gap in the knowledge of plasma cells in teleost fish and provides critical insights into the conserved evolution of IgM+ plasma cells in vertebrates.

12.
Aging (Albany NY) ; 12(2): 1159-1170, 2020 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-31955154

RESUMO

Hydrogen peroxide (H2O2) induces oxidative injury to human osteoblasts. The expression and potential function of circular RNA HIPK3 (circHIPK3) in H2O2-treated human osteoblasts were tested. We show that H2O2 significantly downregulated circHIPK3 in OB-6 cells and primary human osteoblasts. Furthermore, circHIPK3 levels were decreased in the necrotic femoral head tissues of dexamethasone-treated patients. In OB-6 osteoblastic cells and primary human osteoblasts, forced overexpression of circHIPK3 by a lentiviral construct alleviated H2O2-induced viability reduction, cell death and apoptosis. Contrarily, circHIPK3 silencing by targeted shRNA potentiated H2O2-induced cytotoxicity in OB-6 cells and primary human osteoblasts. Moreover, circHIPK3 downregulation by H2O2 induced miR-124 accumulation in OB-6 cells and primary human osteoblasts. On the contrary, miR-124 inhibition by transfection of the miR-124 inhibitor protected human osteoblasts from H2O2. Importantly, forced overexpression of miR-124 by transfection of the miR-124 mimic induced significant cytotoxicity in OB-6 cells and primary human osteoblasts. H2O2 downregulated miR-124's targets, cyclin dependent kinase 6 and Rho-Associated Protein Kinase 1, in human osteoblasts. In conclusion circHIPK3 downregulation mediates H2O2-induced cytotoxicity in human osteoblasts.

13.
Aging (Albany NY) ; 12(2): 1433-1445, 2020 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-31954374

RESUMO

Patients with schizophrenia (SCZ) exhibit higher suicide rates than the general population. However, the molecular mechanism remains poorly understood. Tumor necrosis factor (TNF)-alpha polymorphisms have been repeatedly indicated to play a pathogenetic role in various mental disorders, but none of these studies focused on the susceptibility to suicidal behavior in SCZ. We recruited 1087 chronic inpatients with SCZ and 576 controls to assess the psychopathological symptoms of SCZ using the Positive and Negative Syndrome Scale scales. We selected 2 polymorphisms (-308G>A and -1031C>T) in the TNF-alpha gene and analyzed their associations with SCZ and suicide. Our results showed that TNF-alpha -308G>A and -1031C>T were not related to SCZ and suicide. However, we found that suicide attempters with the C allele carriers exhibited suicidal behaviors significantly later than those with TT genotype in the SCZ patients. The haplotype containing the T allele of the -1031 was significantly associated with the age of suicide initiation. Further logistic regression analysis showed that -1031C>T interacted with psychopathological symptoms and drinking, age of smoking, and related to the initiation age of suicide attempts. Our study demonstrated that the TNF-alpha variants may affect the age at which suicide attempts started among SCZ suicide attempters.

14.
Schizophr Res ; 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31987695

RESUMO

Diabetes is one of the most common comorbid diseases in patients with schizophrenia. The present study examined the prevalence of diabetes and its clinical correlates in a large sample of Chinese patients with schizophrenia, which has not been examined systemically. In this cross-sectional study, a total of 1189 patients (males/females = 938/251; average age: 48.51 ± 10.09 years) were recruited. Fasting blood samples were collected to diagnose diabetes. Psychiatric symptoms were measured with the Positive and Negative Syndrome Scale (PANSS). The prevalence of diabetes was 12.53% with a significant gender difference (males: 10.87% versus females: 18.73%). Compared to patients without diabetes, those with diabetes were older, had a later age of onset, had a higher BMI, had higher positive symptom scores and had higher level of metabolic indices, including triglyceride, cholesterol and HDL cholesterol. After stepwise binary logistic regression analysis, age, BMI, and triglyceride level remained significantly associated with diabetes. This study suggests that diabetes occur with high prevalence in Chinese schizophrenia patients. In addition, age, BMI, and triglyceride level possibly are useful markers predicting an increased risk for diabetes.

15.
J Affect Disord ; 263: 507-515, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31759671

RESUMO

BACKGROUND: The coexistence of subclinical hypothyroidism (SCH) and depression has been intensively examined in the patients receiving thyroxine or antidepressant treatment. This study aimed to investigate the prevalence and clinical correlates of severe SCH in Chinese first-episode drug naïve patients with major depressive disorder (MDD). METHODS: Using a cross-sectional design, we recruited a total of 1706 MDD patients. Depressive symptoms were evaluated using the 17-item Hamilton Depression Rating Scale (HAMD). Severity of anxiety and psychiatric symptoms were evaluated by the Hamilton Anxiety Rating Scale (HAMA) and the Positive and Negative Syndrome Scale (PANSS), respectively. Serum thyroid function parameters were measured by a chemiluminescence immunoassay. Based on the serum thyroid stimulating hormone (TSH) level, SCH was further divided into mild (TSH < 10 mIU/L) and severe SCH (TSH ≥ 10 mIU/L). RESULTS: More patients with severe SCH had severe anxiety, psychotic symptoms, suicide attempts (all p < 0.001), compared with those without severe SCH. Logistic regression showed that suicide attempts and psychiatric symptoms were associated with severe SCH (both p < 0.001). Multiple linear regression showed that age (p < 0.05), BMI (p < 0.001), HAMD score (p < 0.001), HAMA score (p < 0.001), PANSS positive subscore (p = 0.001) and CGI score (p = 0.001) were associated with TSH levels. CONCLUSION: Our findings suggest that suicide attempts and psychiatric symptoms may be associated with severe SCH. Moreover, severe anxiety, depressive and psychotic symptoms, as well as older age and higher BMI are possibly related to elevated TSH levels.

16.
Schizophr Res ; 215: 105-112, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31780341

RESUMO

OBJECTIVE: Cognitive impairment is a core symptom of schizophrenia (SCZ); however, its pathophysiological mechanisms remain unclear. The sensory gating (SG) deficits reflected by P50 inhibition are recurring in SCZ, and this inhibition may be related to the cognitive deficits seen in these individuals. This study aimed to investigate the relationship between P50 inhibition and cognitive dysfunction in SCZ, which has not been fully investigated up to this point. METHODS: A total of 270 individuals with chronic SCZ and 116 healthy controls were enrolled in the study. Psychopathology of SCZ was rated by the positive and negative syndrome scale (PANSS), while cognitive function and P50 inhibition of subjects were assessed by the MATRICS Consensus Cognitive Battery (MCCB) and the electroencephalography system. RESULTS: The MCCB total and its 10 index scores were significantly lower in patients than those in healthy controls (all p < 0.001). SCZ patients had a lower amplitude of S1, and higher P50 ratio than healthy controls (both p < 0.01). However, there were no significant correlations between the P50 ratio and any of the PANSS total and its subscale scores in SCZ patients (all p > 0.05). Moreover, no correlation was found between the P50 components and the MCCB scores (all p > 0.05). CONCLUSIONS: Our findings suggest that the P50 inhibition deficits occur in Chinese individuals with SCZ, which may not be associated with their clinical symptoms and cognitive impairment.

17.
Psychoneuroendocrinology ; 111: 104473, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31655452

RESUMO

Executive dysfunction is increasingly recognized as one of the widely observed dimensions of cognitive impairments in the course of schizophrenia (SCZ). However, the potential molecular pathological mechanisms remain elusive. Previous studies have demonstrated that decreased brain-derived neurotrophic factor (BDNF) and oxidative damage may be associated with the psychopathology and cognitive impairment of SCZ. The present study aims to assess whether the interaction between BDNF and oxidative damage is involved in the disruption of executive function (EF) in patients with chronic SCZ. Serum BDNF and plasma oxidative stress markers were measured in 189 patients and 60 control subjects. EFs were evaluated by Wisconsin card sorting tests (WCST), Stroop word/color test (Stroop), and verbal fluency tests (VFT). The results showed that patients performed worse in the VFT, WCST and Stroop tests than healthy subjects. Moreover, patients had lower activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) and lower BDNF levels, but higher malondialdehyde (MDA) levels than healthy controls. In patients, BDNF was negatively correlated with SOD (p < 0.01). For patients, catalase (CAT) activity was negatively associated with WCST error score (p = 0.02) and BDNF was positively correlated to VFT score (p = 0.02). However, all these correlations between biomarkers and EF domains did not pass Bonferroni corrections. Finally, multiple regression analyses identified BDNF × SOD activity and BDNF × MDA as influencing factors for VFT score in patients (both p < 0.05). Our results highlight the complex interplay between OS parameters and BDNF in the pathophysiology of EF impairment in SCZ, consistent with its neurodevelopmental hypothesis.

18.
Dev Comp Immunol ; 105: 103576, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31846686

RESUMO

Tumor necrosis factor-α (TNF-α) plays crucial roles in cell development, proliferation, apoptosis, inflammation, and immunity. TNF-α genes have been identified in various fish species, however, their biological functions remain to be further clarified. In this study, we identified a novel TNF-α homologue (LcTNF-α2) from large yellow croaker (Larimichthys crocea), which shares a low amino acid sequence identity to the previously reported large yellow croaker TNF-α (LcTNF-α1). The open reading frame of LcTNF-α2 is 714 nucleotides long, encoding a peptide of 237 amino acids (aa). The deduced LcTNF-α2 protein contains a 23-aa transmembrane region, a TACE restriction site at residues T71/L72, a TNF family signature (I108- F135), and two conserved cysteine residues (C39 and C179), as found in other known TNF-α sequences. Both LcTNF-α1 and LcTNF-α2 genes were constitutively expressed in all examined tissues and significantly up-regulated in the spleen and head kidney by Vibrio alginolyticus. Their transcripts were also detected in primary head kidney monocytes/macrophages (MO/Mϕs), lymphocytes (PKLs), granulocytes (PKGs), and large yellow croaker head kidney (LYCK) cell line and significantly increased in these cell types by inactivated Vibrio alginolyticus. Recombinant LcTNF-α1 and LcTNF-α2 proteins (rLcTNF-α1 and rLcTNF-α2) produced in Pichia pastoris not only significantly increased the production of reactive oxygen species (ROS), but also promoted the expression of proinflammatory cytokines (IL-1ß, IL-6,IL-8, and TNF-α1) in MO/Mϕs from large yellow croaker. Even more, after stimulation with rLcTNF-α1 and rLcTNF-α2, the production of nitrogen oxide (NO) and the expression of inducible NO synthase (iNOS) gene were significantly up-regulated. However, only rLcTNF-α1 remarkedly enhanced the phagocytosis of MO/Mϕs and increased the expression of TNF-α2 in MO/Mϕs. These results therefore indicated that LcTNF-α1 and LcTNF-α2 both play roles in promoting activation of head kidney MO/Mϕs.

19.
Sci Rep ; 9(1): 19252, 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31848444

RESUMO

Post-traumatic stress disorder (PTSD) is a psychiatric syndrome that occurs after trauma exposure. Neurotransmitters such as dopamine and oxytocin have been reported to be involved in neuropathology of PTSD. Previous studies indicated that the dopamine-oxytocin interaction may contribute to behavioral disorders. Thus, exploring the epistasis (gene-gene interaction) between oxytocinergic and dopaminergic systems might be useful to reveal the genetic basis of PTSD. In this study, we analyzed two functional single nucleotide polymorphisms (SNPs), rs2268498 for oxytocinergic gene OXTR and rs1801028 for dopaminergic gene DRD2 based on putative oxytocin receptor-dopamine receptor D2 (OTR-DR2) heterocomplex in a Chinese cohort exposed to the 2008 Wenchuan earthquake (156 PTSD cases and 978 controls). Statistical analyses did not find any single variant or gene-environment interaction (SNP × earthquake-related trauma exposure) associated with provisional PTSD diagnosis or symptoms. An OXTR-DRD2 interaction (rs2268498 × rs1801028) was identified to confer risk of provisional PTSD diagnosis (OR = 9.18, 95% CI = 3.07-27.46 and P = 7.37e-05) and further subset analysis indicated that rs2268498 genotypes controlled the association directions of rs1801028 and rs1801028 genotypes also controlled the association directions of rs2268498. Rs2268498 × rs1801028 is also associated with PTSD symptoms (P = 0.043). Our study uncovered a genetic and putative function-based contribution of dopaminergic-oxytocinergic system interaction to PTSD.

20.
Cell Death Dis ; 10(12): 888, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31767834

RESUMO

Activation of nuclear-factor-E2-related factor 2 (Nrf2) cascade can alleviate dexamethasone (DEX)-induced oxidative injury and death of human osteoblasts. A recent study has shown that phosphoglycerate kinase 1 (PGK1) inhibition/depletion will lead to Kelch-like ECH-associated protein 1 (Keap1) methylglyoxal modification, thereby activating Nrf2 signaling cascade. Here, in OB-6 osteoblastic cells and primary human osteoblasts, PGK1 silencing, by targeted shRNA, induced Nrf2 signaling cascade activation, causing Nrf2 protein stabilization and nuclear translocation, as well as increased expression of ARE-dependent genes (HO1, NQO1, and GCLC). Functional studies demonstrated that PGK1 shRNA largely attenuated DEX-induced oxidative injury and following death of OB-6 cells and primary osteoblasts. Furthermore, PGK1 knockout, by the CRISPR/Cas9 method, similarly induced Nrf2 signaling activation and protected osteoblasts from DEX. Importantly, PGK1 depletion-induced osteoblast cytoprotection against DEX was almost abolished by Nrf2 shRNA. In addition, Keap1 shRNA mimicked and nullified PGK1 shRNA-induced anti-DEX osteoblast cytoprotection. At last we show that PGK1 expression is downregulated in human necrotic femoral head tissues of DEX-taking patients, correlating with HO1 depletion. Collectively, these results show that PGK1 depletion protects human osteoblasts from DEX via activation of Keap1-Nrf2 signaling cascade.

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