Publications by authors named "Zezhi Li"

78 Publications

Sex difference in comorbid depression in first-episode and drug-naïve patients with schizophrenia: Baseline results from the Depression in Schizophrenia in China study.

Psychosom Med 2021 Aug 13. Epub 2021 Aug 13.

Department of Neurology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Qingdao Mental Health Center, Qingdao University, Qingdao, China Shenzhen Kangning Hospital, Shenzhen, Guangdong, China. Department of Neurosurgery, Shanghai Changhai Hospital, Shanghai, China. Shanghai Mental Health Center, Shanghai, China Department of Psychiatry, The First Clinical Medical College, Shanxi Medical University, Taiyuan, China Department of Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China Department of Psychology, University of Chinese Academy of Sciences, Beijing, China.

Objective: Comorbid depression is common in schizophrenia, and sex differences are prominent in many aspects of schizophrenia. However, few studies have investigated sex difference in comorbid depression in schizophrenia. This large sample study aimed to investigate sex differences in first-episode drug-naive (FEDN) patients with schizophrenia comorbid major depressive episode (MDE) (SZ-MDE).

Methods: A total of 996 FEDN patients with schizophrenia (472 males/524 females) were recruited. The 17-item Hamilton Depression Rating Scale (HAMD-17) and Positive and Negative Syndrome Scale (PANSS) were applied.

Results: There was no difference in the prevalence of comorbid MDE between male and female patients with schizophrenia. Among SZ-MDE patients, men had more severe psychotic symptoms (scores of PANSS total scale, negative scale, and general psychopathology scale), more severe depressive symptoms and higher proportion of severe depression than women (all p < 0.001). The early onset age of schizophrenia, smoking and PANSS positive score were the risk factors for comorbid MDE only in female patients with schizophrenia (all p < 0.05). Furthermore, in female patients with SZ-MDE, smoking was associated with the severity category of depression (p = 0.001, OR = 2.70). Multiple variable regression demonstrated HAMD17 score correlated with PANSS general psychopathology (p = 0.01) and total scores (p = 0.04) in female SZ-MDE.

Conclusions: Our results indicate sex differences in proportion of severe depression, clinical symptoms, and factors of comorbid MDE in FEDN patients with schizophrenia. These sex differences have clinical implications for the treatment of depression as related to the nature and severity of psychopathological symptoms in patients with schizophrenia.
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http://dx.doi.org/10.1097/PSY.0000000000000998DOI Listing
August 2021

Reliability and validity of the Chinese version of the CUDOS-M in patients with mood disorders: A multicenter study across China.

J Affect Disord 2021 Nov 18;294:723-729. Epub 2021 Jul 18.

Division of Mood Disorders, Hongkou District Mental Health Center, Shanghai, China; School of Medicine, Shanghai University, Shanghai, China. Electronic address:

Background: A useful scale for identification of mixed features in major depressive episodes (MDE) patients is urgent in China. This study aimed to evaluate the reliability and validity of the Chinese version of the Clinically Useful Depression Outcome Scale supplemented with questions for the DSM-5 mixed features specifier (Chinese-CUDOS-M) in MDE patients.

Methods: A total of 152 MDE patients were recruited and assessed using Chinese-CUDOS-M, Patient Health Questionnaire-9 (PHQ-9) and 32-item Hypomania Checklist (HCL-32). Principal component analysis (PCA) and exploratory factor analysis (EFA) were conducted. The predictive validity was calculated by the area under the receiver operating characteristic curve (AUROC).

Results: The Cronbach's alpha of Chinese-CUDOS-M was 0.85. PCA showed three common factors with eigenvalue greater than 1; the eigenvalue of factor I was 4.96, with 38.1% of variance explanation. Chinese-CUDOS-M depression subscale was associated with PHQ-9 (r = 0.83, p<0.01), and manic subscale was associated with HCL-32 (r = 0.73, p< 0.01). AUROC of the Chinese-CUDOS-M for patients with mixed depression was 0.90 (95%CI: 0.85-0.95), with a cut-off value of 7, sensitivity of 0.95, and specificity of 0.73. Furthermore, AUROC was 0.88 in patients with major depressive disorder (MDD), with a cut-off value of 7, sensitivity of 0.96, and specificity of 0.71. AUROC was 0.92 in bipolar disorder (BD) depression patients, with a cut-off value of 9, sensitivity of 0.89, and specificity of 0.87.

Conclusion: Our study shows that the Chinese-CUDOS-M can identify mixed features in both MDD and BD depression with satisfactory reliability and validity.
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http://dx.doi.org/10.1016/j.jad.2021.07.014DOI Listing
November 2021

HDAC6-mediated Hsp90 deacetylation reduces aggregation and toxicity of the protein alpha-synuclein by regulating chaperone-mediated autophagy.

Neurochem Int 2021 Oct 21;149:105141. Epub 2021 Jul 21.

Department of Neurology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. Electronic address:

Histone deacetylase 6 (HDAC6) has been shown to control major cell response pathways to the cytotoxic ubiquitinated aggregates in some protein aggregation diseases. However, it is not well known whether HDAC6 affects the aggregation process of α-synuclein (α-syn) in Parkinson's disease (PD). Previously, we demonstrated that HDAC6 inhibition exacerbated the nigrostriatal dopamine neurodegeneration and up-regulated α-syn oligomers in a heat shock protein 90 (Hsp90)-dependent manner in PD mouse model. Here, we further showed that HDAC6 overexpression partly improved the behavior deficits of the PD model and alleviated the nigrostriatal dopamine (DA) neurons injury. Furthermore, HDAC6 was found to regulate α-syn oligomers levels through activation of chaperone-mediated autophagy (CMA). During this process, Hsp90 deacetylation mediated the crosstalk between HDAC6 and lysosome-associated membrane protein type 2A. Liquid chromatography-tandem mass spectrometry and mutational analysis showed that acetylation status Hsp90 at the K489 site was a strong determinant for HDAC6-induced CMA activation, α-syn oligomers levels, and cell survival in the cell model of PD. Therefore, our findings uncovered the mechanism of HDAC6 in the PD model that HDAC6 regulated α-syn oligomers levels and DA neurons survival partly through modulating CMA, and Hsp90 deacetylation at the K489 site mediated the crosstalk between HDAC6 and CMA. HDAC6 and its downstream effectors appear as key modulators of the cytotoxic α-syn aggregates, which deserve further investigations to evaluate their values as potential therapeutic targets in PD.
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http://dx.doi.org/10.1016/j.neuint.2021.105141DOI Listing
October 2021

Differences in patterns of metabolic abnormality and metabolic syndrome between early-onset and adult-onset first-episode drug-naive schizophrenia patients.

Psychoneuroendocrinology 2021 Jun 29;132:105344. Epub 2021 Jun 29.

CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China. Electronic address:

Although metabolic abnormalities and metabolic syndrome (MetS) often occur in schizophrenia, few studies have investigated them in early-onset schizophrenia (EOS) patients. To our knowledge, this was the first to compare clinical correlates of metabolic abnormalities between first-episode drug-naïve (FEDN) EOS and adult-onset schizophrenia (AOS) patients. A total of 489 Chinese FEDN schizophrenia patients (116 EOS and 373 AOS) and 451 healthy controls were recruited in this cross-sectional study. Blood pressure, waist circumference (WC), Body mass index (BMI), total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDLC), low density lipoprotein cholesterol (LDLC), glucose, hemoglobin A1c (HbA1c), insulin and insulin resistance were measured. The Positive and Negative Syndrome Scale (PANSS) was applied to evaluate the clinical symptoms of schizophrenia patients, and higher scores on PANSS indicate increased severity. EOS patients had lower rates of: MetS, elevated WC, hypertriglyceridemia, hypercholesterolemia, and hyper-LDLC than EOS patients (all p < 0.05). In EOS patients, WC was positively associated with PANSS general psychopathology score (p = 0.04). In AOS patients, WC (p = 0.01; p = 0.02) and glucose (p < 0.001; p < 0.001) were positively associated with PANSS general psychopathology and total score. HOMA-IR was positively associated with PANSS total score (p = 0.04). Systolic BP, triglycerides and HDLC were main contributors to MetS in AOS (all p < 0.05), but not in EOS. BMI was a risk factor of MetS in EOS, while BMI and HOMA-IR were risk factors of MetS in AOS (all p < 0.05). Our results indicate differences in metabolic abnormalities patterns, risk factors and their association with clinical characteristics between Chinese EOS and AOS patients. DATA AVAILABILITY STATEMENT: The datasets that support the findings of this study are not publically available due to ongoing analyses for further publications, but are available from the corresponding author X.Z. upon reasonable request.
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http://dx.doi.org/10.1016/j.psyneuen.2021.105344DOI Listing
June 2021

Comorbid major depression in first-episode drug-naïve patients with schizophrenia: Analysis of the Depression in Schizophrenia in China (DISC) study.

J Affect Disord 2021 Nov 5;294:33-38. Epub 2021 Jul 5.

CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing, China. Electronic address:

Background: Depression is very common in patients with schizophrenia, but few studies have investigated the diagnosed major depressive episode (MDE) in first episode and drug naive (FEDN) schizophrenia. To our best knowledge, this is the first large sample study to examine the prevalence, clinical correlates and associated factors of diagnosed MDE in FEDN schizophrenia, as well as the relationship between depressive symptoms and psychopathological symptoms in these schizophrenia patients.

Methods: A total of 996 FEDN schizophrenia patients were recruited. The 17-item Hamilton Depression Rating Scale (HAMD17) and Positive and Negative Syndrome Scale (PANSS) were used to assess the severity of depression and psychopathology, respectively.

Results: Our results demonstrated that MDE coexisted in nearly half (49.30%) of FEDN schizophrenia patients. Male gender, smoking, PANSS general psychopathology and early age of onset were associated with MDE in patients with FEDN schizophrenia (all p<0.05). In schizophrenia patients with MDE, oridinal logistic regression showed that men (OR=6.65, 95%CI: 4.12-10.45, p<0.001) and smoking (OR=1.94, 95%CI: 1.25-3.01, p=0.003) were positively associated with severity category of depression (all p<0.05), while multivariate regression showed that HAMD17 total score was significantly associated with the PANSS general psychopathology (B=0.06, t=2.72, p=0.007) and total scores (B=0.04, t=2.57, p=0.01).

Conclusion: Our study shows that the prevalence of comorbid MDE is high in FEDN schizophrenia patients. Some demographic and clinical variables are associated with the severity of depression in these schizophrenia patients.
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http://dx.doi.org/10.1016/j.jad.2021.06.075DOI Listing
November 2021

Fear and depressive symptoms amid COVID-19: A cross-sectional pilot study among adult population in Bangladesh.

Heliyon 2021 Jul 24;7(7):e07395. Epub 2021 Jun 24.

Department of Neurosurgery, Changhai Hospital, Shanghai, China.

Background: Fear is a primary emotional reaction to the deadly coronavirus disease which might be an associated factor for developing depressive symptoms. This study aimed to assess the level and associated factors of fear and depression amid the COVID-19 pandemic among the adult population of Bangladesh.

Methods: After providing informed consent, 1050 participants completed the cross-sectional online survey tool. Depressive symptoms and fear were assessed through the PHQ-9 and validated fear of COVID-19 scale (FCV-19S), respectively. Linear regression analysis was performed to predict potential factors of fear and depression.

Results: The study finds that females had higher scores for fear of COVID-19 scale (β1' = 1.81; 95% CI: 1.15 to 2.47) and Patient Health Questionnaire (β2' = 1.92; 95% CI: 0.95 to 2.88) than their male counterpart. Respondents considering the virus to be extremely dangerous had higher scores for FCV-19S (β1' = 1.55; 95% CI: 0.66 to 2.44) and PHQ-9 (β2 = 1.59; 95% CI: 0.25 to 2.92). Similarly, respondents considering themselves unsafe and very worried about the virus had increased scores for both FCV-19S and PHQ-9. On other hand, people those were reluctant to use masks (β1' = -1.58; 95% CI: -3.12 to -0.04) or seek doctors' advice (β1' = -0.93; 95% CI: -1.83 to -0.02) if COVID-19 symptoms appear, had comparatively lower scores for FCV-19S.

Conclusions: Fear of COVID-19 and depression were found to be associated with some specific knowledge, attitude & preparedness towards COVID-19 which should be adequately addressed in public health strategies to prevent the virus.
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http://dx.doi.org/10.1016/j.heliyon.2021.e07395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225288PMC
July 2021

Smoking affects the patterns of metabolic disorders and metabolic syndrome in patients with first-episode drug-naive schizophrenia - a large sample study based on Chinese Han population.

Int J Neuropsychopharmacol 2021 Jun 21. Epub 2021 Jun 21.

Department of Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China.

Objective: Although metabolic disorders and smoking are common in schizophrenia, few studies investigated the effects of smoking on metabolic disorders or metabolic syndrome (MetS) in schizophrenia patients, especially in first-episode drug-naïve (FEDN) patients. To investigate the differences in metabolic disorders and MetS between smoking and non-smoking FEDN schizophrenia patients.

Methods: A total of 428 FEDN schizophrenia patients and 435 controls were recruited. Blood pressure, waist circumference, body mass index (BMI), lipid profiles and glucose metabolism were measured. The psychopathology was evaluated by Positive and Negative Syndrome Scale (PANSS).

Results: FEDN schizophrenia patients had higher smoking rate than controls (23.8% vs. 14.0%, p<0.001). After adjusting for confounding variables, the prevalence of MetS, overweight, hypertension, hypertriglyceridemia, elevated insulin and insulin resistance in smoking patients were higher than those in non-smoking patients, while overweight and hypertension in the smoking controls were higher than those in non-smoking controls (all p<0.05). In smoking patients, triglyceridemia, HDLC and fasting blood glucose were the main contributing components to MetS, while in non-smoking patients, waist circumference, systolic BP, triglyceridemia, HDLC and fasting blood glucose were the main contributing components to MetS. In smoking patients, BMI and HOMA-IR were associated factors of MetS (both p<0.05). In non-smoking patients, sex, BMI, insulin and HOMA-IR were associated factors of MetS (all p<0.05).

Conclusions: Our study indicates that smoking schizophrenia patients have a higher prevalence of MetS and metabolic disorders than non-smoking patients. Moreover, smoking and non-smoking patients have different contributing components and associated factors for MetS.
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http://dx.doi.org/10.1093/ijnp/pyab038DOI Listing
June 2021

Correction to: Major Depressive Disorder: Advances in Neuroscience Research and Translational Applications.

Neurosci Bull 2021 Jun;37(6):904

Clinical Research Center and Division of Mood Disorders of Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China.

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http://dx.doi.org/10.1007/s12264-021-00694-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192640PMC
June 2021

Gene expression signatures differentiating major depressive disorder from subsyndromal symptomatic depression.

Aging (Albany NY) 2021 05 8;13(9):13124-13137. Epub 2021 May 8.

Clinical Research Center, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.

Subsyndromal symptomatic depression (SSD) and major depressive disorder (MDD) have been classified as distinct diseases, due to their dissimilar gene expression profiles and responses to venlafaxine. To identify specific biomarkers of these two diseases, we conducted a secondary analysis of the gene expression signatures of SSD patients, MDD patients and healthy controls (n=8/group) from the study of Yi et al. Global, individual, specific, enrichment and co-expression analyses were used to compare the transcriptomic profiles of peripheral blood lymphocytes from the three groups. The global and individual analyses revealed that different genes were up- and downregulated in the SSD and MDD groups. Through our specific analysis, we identified 1719 and 3278 differentially expressed genes specifically associated with MDD and SSD, respectively. Enrichment and co-expression analyses demonstrated that the genes specific to MDD were enriched in pathways associated with hormone levels and immune responses, while those specific to SSD were associated with immune function. The specific hub gene for the MDD co-expression network was transmembrane protein 132B (TMEM132B), while the hub genes for SSD were actin-related protein 2/3 complex (ARPC2) and solute carrier family 5 member 5 (SLC5A5). This bioinformatic analysis has provided potential biomarkers that can distinguish SSD from MDD.
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http://dx.doi.org/10.18632/aging.202995DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148500PMC
May 2021

PAID study design on the role of PKC activation in immune/inflammation-related depression: a randomised placebo-controlled trial protocol.

Gen Psychiatr 2021 5;34(2):e100440. Epub 2021 Apr 5.

Clinical Research Center and Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Inflammation that is mediated by microglia activation plays an important role in the pathogenesis of depression. Microglia activation can lead to an increase in the levels of proinflammatory cytokines, including TNF-α, which leads to neuronal apoptosis in the specific neural circuits of some brain regions, abnormal cognition and treatment-resistant depression (TRD). Protein kinase C (PKC) is a key regulator of the microglia activation process. We assume that the abnormality in PKC might result in abnormal microglia activation, neuronal apoptosis, significant changes in emotional and cognitive neural circuits, and TRD. In the current study, we plan to target at the PKC signal pathway to improve the TRD treatment outcome.

Methods And Analysis: This is a 12-week, ongoing, randomised, placebo-controlled trial. Patients with TRD (N=180) were recruited from Shanghai Mental Health Center, Shanghai Jiao Tong University. Healthy control volunteers (N=60) were recruited by advertisement. Patients with TRD were randomly assigned to 'escitalopram+golimumab (TNF-α inhibitor)', 'escitalopram+calcium tablet+vitamin D (PKC activator)' or 'escitalopram+placebo' groups. We define the primary outcome as changes in the 17-item Hamilton Depression Rating Scale (HAMD-17). The secondary outcome is defined as changes in anti-inflammatory effects, cognitive function and quality of life.

Discussion: This study might be the first randomised, placebo-controlled trial to target at the PKC signal pathway in patients with TRD. Our study might help to propose individualised treatment strategies for depression.

Trial Registration Number: The trial protocol is registered with ClinicalTrials.gov under protocol ID 81930033 and ClinicalTrials.gov ID NCT04156425.
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http://dx.doi.org/10.1136/gpsych-2020-100440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8030460PMC
April 2021

PAID study design on the role of PKC activation in immune/inflammation-related depression: a randomised placebo-controlled trial protocol.

Gen Psychiatr 2021 5;34(2):e100440. Epub 2021 Apr 5.

Clinical Research Center and Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Inflammation that is mediated by microglia activation plays an important role in the pathogenesis of depression. Microglia activation can lead to an increase in the levels of proinflammatory cytokines, including TNF-α, which leads to neuronal apoptosis in the specific neural circuits of some brain regions, abnormal cognition and treatment-resistant depression (TRD). Protein kinase C (PKC) is a key regulator of the microglia activation process. We assume that the abnormality in PKC might result in abnormal microglia activation, neuronal apoptosis, significant changes in emotional and cognitive neural circuits, and TRD. In the current study, we plan to target at the PKC signal pathway to improve the TRD treatment outcome.

Methods And Analysis: This is a 12-week, ongoing, randomised, placebo-controlled trial. Patients with TRD (N=180) were recruited from Shanghai Mental Health Center, Shanghai Jiao Tong University. Healthy control volunteers (N=60) were recruited by advertisement. Patients with TRD were randomly assigned to 'escitalopram+golimumab (TNF-α inhibitor)', 'escitalopram+calcium tablet+vitamin D (PKC activator)' or 'escitalopram+placebo' groups. We define the primary outcome as changes in the 17-item Hamilton Depression Rating Scale (HAMD-17). The secondary outcome is defined as changes in anti-inflammatory effects, cognitive function and quality of life.

Discussion: This study might be the first randomised, placebo-controlled trial to target at the PKC signal pathway in patients with TRD. Our study might help to propose individualised treatment strategies for depression.

Trial Registration Number: The trial protocol is registered with ClinicalTrials.gov under protocol ID 81930033 and ClinicalTrials.gov ID NCT04156425.
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http://dx.doi.org/10.1136/gpsych-2020-100440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8030460PMC
April 2021

Metformin Attenuates the Metabolic Disturbance and Depression-like Behaviors Induced by Corticosterone and Mediates the Glucose Metabolism Pathway.

Pharmacopsychiatry 2021 May 25;54(3):131-141. Epub 2021 Feb 25.

Department of Neurology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Metabolism disturbances are common in patients with depression. The drug metformin has been reported to exhibit antidepressant activity. The purpose of this study was to investigate metabolism disturbances induced by corticosterone (CORT) and determine if metformin can reverse these effects and their accompanying depression-like behaviors.

Methods: Rats were exposed to corticosterone with or without metformin administration. Depression-like behaviors were tested. Gene expression was confirmed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis. In addition, the metabolites were quantified by LC-MS/MS analysis.

Results: Metformin attenuated the depression-like behaviors induced by CORT. Furthermore, metformin reversed disturbances in body weight, serum glucose, and triglyceride levels, as well as hepatic TG levels induced by CORT. Metformin normalized the alterations in the expression of glucose metabolism-related genes (, , , , , , , ) and insulin resistance-related genes (, ) in the muscles and livers of rats induced by CORT. Metabolomic analysis showed that metformin reversed the effects of CORT on 11 metabolites involved in the pathways of the tricarboxylic acid cycle, glycolysis, and gluconeogenesis (3-phospho-D-glycerate, β-D-fructose 6-phosphate, D-glucose 6-phosphate, and pyruvate).

Conclusion: Our findings suggest that metformin can attenuate metabolism disturbances and depression-like behaviors induced by CORT mediating the glucose metabolism pathway.
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http://dx.doi.org/10.1055/a-1351-0566DOI Listing
May 2021

Major Depressive Disorder: Advances in Neuroscience Research and Translational Applications.

Neurosci Bull 2021 Jun 13;37(6):863-880. Epub 2021 Feb 13.

Clinical Research Center and Division of Mood Disorders of Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China.

Major depressive disorder (MDD), also referred to as depression, is one of the most common psychiatric disorders with a high economic burden. The etiology of depression is still not clear, but it is generally believed that MDD is a multifactorial disease caused by the interaction of social, psychological, and biological aspects. Therefore, there is no exact pathological theory that can independently explain its pathogenesis, involving genetics, neurobiology, and neuroimaging. At present, there are many treatment measures for patients with depression, including drug therapy, psychotherapy, and neuromodulation technology. In recent years, great progress has been made in the development of new antidepressants, some of which have been applied in the clinic. This article mainly reviews the research progress, pathogenesis, and treatment of MDD.
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http://dx.doi.org/10.1007/s12264-021-00638-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192601PMC
June 2021

Disturbances of affective cognition in mood disorders.

Sci China Life Sci 2021 Jun 8;64(6):938-941. Epub 2021 Feb 8.

Clinical Research Center & Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China.

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http://dx.doi.org/10.1007/s11427-020-1898-2DOI Listing
June 2021

Disturbances of affective cognition in mood disorders.

Sci China Life Sci 2021 Jun 8;64(6):938-941. Epub 2021 Feb 8.

Clinical Research Center & Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China.

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http://dx.doi.org/10.1007/s11427-020-1898-2DOI Listing
June 2021

The antitumor role of a newly discovered α-d-glucan from Holotrichia diomphalia Bates as a selective blocker of aldolase A.

Carbohydr Polym 2021 Mar 18;255:117532. Epub 2020 Dec 18.

Shaanxi Key Laboratory of Natural Products & Chemical Biology, School of Chemistry & Pharmacy, Northwest A&F University, Yangling, 712100, China; Department of Pharmacology and Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, School of Pharmacy, Fourth Military Medical University, Xi'an, China. Electronic address:

Aldolase A (ALDOA) facilitated aerobic glycolysis in cancer cells is a potential target in the treatment of hepatocellular carcinoma (HCC). However, only few effective inhibitors of ALDOA have been reported until now. In this research, we found a polysaccharide called HDPS-4II from Holotrichia diomphalia Bates, which can specifically bind to ALDOA with a dissociation constant of 2.86 μM. HDPS-4II with a molecular weight of 19 kDa was a linear triple-helix glucan composed of ɑ-d-1,4-Glcp and ɑ-d-1,6-Glcp in a ratio of 1.0:10.0. HDPS-4II significantly inhibited aldolase enzyme activity, glycolysis, and further inhibited the expression of phosphorylated AMPKα in HCC cells. Through analyzing ALDOA-overexpressing and -knockdown cells, it was confirmed that ALDOA mediated the viability and glycolysis inhibition of HDPS-4II. Moreover, HDPS-4II administration markedly inhibited tumor growth in mice xenografted with HCCs. These findings suggest that HDPS-4II, as an ALDOA antagonist, is a promising remedy in the treatment and prevention of HCC.
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http://dx.doi.org/10.1016/j.carbpol.2020.117532DOI Listing
March 2021

TRIM27-mediated ubiquitination of PPARγ promotes glutamate-induced cell apoptosis and inflammation.

Exp Cell Res 2021 03 30;400(1):112437. Epub 2020 Dec 30.

Neurology Department, Renji Hospital, Shanghai Jiaotong University Medical School, Shanghai, 200127, China. Electronic address:

Neurotoxicity induced by glutamate (Glu) is often used to study the signaling mechanism of neurological disorders. The identification of specific genetic factors that cause Glu-induced neurotoxicity provides evidence for the common pathways of neuronal apoptosis and inflammation. TRIM27 has been found to induce apoptosis and inflammation. Nevertheless, there is little evidence that TRIM27 is associated with Glu-induced neurotoxicity. We found that TRIM27 expression was increased in epilepsy patients and in HT22 cells following Glu treatment. Glu-mediated cell apoptosis, decreased PPARγ expression, and increased levels of cleaved Caspase-3 and IL-1β expression in HT22 cells were significantly inhibited by TRIM27 knockdown. TRIM27 overexpression significantly induced cell apoptosis and expression of cleaved Caspase-3 and IL-1β, but inhibited PPARγ expression in HT22 cells, which were reversed by ROZ, suggesting the involvement of PPARγ in TRIM27-mediated cell apoptosis and inflammation in HT22 cells. Mechanically, TRIM27 ubiquitinates and degrades PPARγ, following induces cleaved Caspase-3 and IL-1β expression. Clinically, increased expression of TRIM27 in epilepsy patients was associated with decreased PPARγ expression. Taken together, our study suggests that TRIM27-mediated ubiquitination of PPARγ promotes Glu-induced HT22 cell apoptosis and IL-1β release.
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http://dx.doi.org/10.1016/j.yexcr.2020.112437DOI Listing
March 2021

Sex differences in metabolic disorder patterns of first-episode drug-naive patients with schizophrenia.

Psychoneuroendocrinology 2021 02 16;124:105061. Epub 2020 Nov 16.

Shenzhen Kangning Hospital, Shenzhen, Guangdong, China; CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing, China. Electronic address:

Although metabolic disorders are common in schizophrenia, few studies investigated sex differences in metabolic disorder. This study aimed to examine the sex differences in the clinical correlates of metabolic disorders and MetS in patients with first-episode drug-naïve (FEDN) schizophrenia. A total of 257 FEDN schizophrenia patients and 118 controls were recruited. Body mass index (BMI), waist circumference (WC) and blood pressure were measured. Fasting blood samples were drawn to detect triglycerides, cholesterol, high density lipoprotein cholesterol (HDLC), low density lipoprotein cholesterol (LDLC), blood glucose, glycosylated hemoglobin (HbA1c) and insulin. The Positive and Negative Syndrome Scale (PANSS) was applied to assess the clinical symptoms. There was sex difference in the prevalence of high BMI and dyslipidemia of schizophrenia patients. Female patients had lower prevalence of high BMI (p = 0.03) and hypertriglyceridemia (p = 0.006), but had higher prevalence of hypo-HDLC (p = 0.005), compared with male patients. Further, there were sex differences in the relationship between metabolic parameters and psychopathological dimensions. In male patients, WC was associated with positive symptoms and negative symptoms (r = 0.26, p = 0.02; r = 0.26, p = 0.02). In female patients, BMI (r = 0.26, p = 0.01), WC (r = 0.30, p = 0.004) and HAb1c were associated with positive symptoms (r = 0.27, p = 0.008). Insulin (r = 0.24, p = 0.02; r = 0.23, p = 0.04) and HOMA-IR (r = 0.29, p = 0.004; r = 0.25, p = 0.02) were associated with positive symptoms and general psychopathology symptoms. The contribution of clinical and metabolic components to MetS was almost same between male and female patients. Our study demonstrates sex difference in metabolic disorder patterns in schizophrenia patients.
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http://dx.doi.org/10.1016/j.psyneuen.2020.105061DOI Listing
February 2021

MicroRNA-195 predicts olanzapine response in drug-free patients with schizophrenia: A prospective cohort study.

J Psychopharmacol 2021 01 4;35(1):23-30. Epub 2020 Dec 4.

Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Disturbances of microRNA-195 have been implicated in the pathogenesis of schizophrenia. However, microRNA-195 levels in schizophrenia are controversial.

Aims: To the best of our knowledge, this is the first study to examine microRNA-195 levels in untreated schizophrenia patients and their relationship to olanzapine response.

Methods: We recruited 81 untreated schizophrenia patients and 96 healthy controls. The patients received 2 months olanzapine treatment. MicroRNA-195 levels in peripheral blood mononuclear cells were measured using quantitative real-time polymerase chain reaction testing. Psychiatric symptoms were assessed using the Positive and Negative Syndrome Scale.

Results: No significant differences in microRNA-195 levels were found between patients and healthy controls ( 0.05). Olanzapine significantly reduced microRNA-195 levels after 2 months treatment ( 0.003). Interestingly, microRNA-195 levels decreased significantly in responders ( 0.010), but not in non-responders ( 0.05). Both baseline microRNA-195 levels ( 0.027,  0.030) and the reduction rate of microRNA-195 levels ( 0.034,  0.044) were positively associated with the reduction rate of Positive and Negative Syndrome Scale total score and general psychopathological subscale score. Multiple stepwise regression analysis revealed that baseline microRNA-195 level was an independent contributor to the reduction in Positive and Negative Syndrome Scale total score and the general psychopathological subscale score ( 0.018,  0.030). Finally, logistic regression analysis suggested that baseline microRNA-195 level can serve as a biomarker for response to olanzapine ( 0.037).

Conclusions: Our data indicate that microRNA-195 level may predict symptomatic improvement and olanzapine response in schizophrenia patients, suggesting that microRNA-195 should be considered as a potential therapeutic target for antipsychotics.
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http://dx.doi.org/10.1177/0269881120959617DOI Listing
January 2021

Public mental health under the long-term influence of COVID-19 in China: Geographical and temporal distribution.

J Affect Disord 2020 12 24;277:893-900. Epub 2020 Aug 24.

CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, 16 Lincui Road, Chaoyang, Beijing 100101, China. Electronic address:

Background: The mental health status caused by major epidemics is serious and lasting. At present, there are few studies about the lasting mental health effects of COVID-19 outbreak. The purpose of this study was to investigate the mental health of the Chinese public during the long-term COVID-19 outbreak.

Methods: A total of 1172 online questionnaires were collected, covering demographical information and 8 common psychological states: depression, anxiety, somatization, stress, psychological resilience, suicidal ideation and behavior, insomnia, and stress disorder. In addition, the geographical and temporal distributions of different mental states were plotted.

Results: Overall, 30.1% of smokers increased smoking, while 11.3% of drinkers increased alcohol consumption. The prevalence rates of depression, anxiety, mental health problems, high risk of suicidal and behavior, clinical insomnia, clinical post-traumatic stress disorder symptoms, moderate-to-high levels of perceived stress were 18.8%, 13.3%, 7.6%, 2.8%, 7.2%, 7.0%, and 67.9%, respectively. Further, the geographical distribution showed that the mental status in some provinces/autonomous regions/municipalities was relatively more serious. The temporal distribution showed that the psychological state of the participants was relatively poorer on February 20, 24 to 26 and March 25, especially on March 25.

Limitations: This cross-sectional design cannot make causal inferences. The snowball sampling was not representative enough.

Conclusion: Our findings suggest that the prevalence rate of mental disorders in the Chinese public is relatively low in the second month of the COVID-19 pandemic. In addition, people's mental state is affected by the geographical and temporal distributions.
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http://dx.doi.org/10.1016/j.jad.2020.08.045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444470PMC
December 2020

The prevalence of psychiatric symptoms of pregnant and non-pregnant women during the COVID-19 epidemic.

Transl Psychiatry 2020 09 19;10(1):319. Epub 2020 Sep 19.

CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.

Coronavirus disease 2019 (COVID-19) is rapidly spreading worldwide, with a staggering number of cases and deaths. However, available data on the psychological impacts of COVID-19 on pregnant women are limited. The purposes of this study were to assess the prevalence of psychiatric symptoms among pregnant women, and to compare them with non-pregnant women. From February 28 to March 12, 2020, a cross-sectional study of pregnant and non-pregnant women was performed in China. The online questionnaire was used to collect information of participants. The mental health status was assessed by patient health questionnaire, generalized anxiety disorder scale, insomnia severity index, somatization subscale of the symptom checklist 90, and post-traumatic stress disorder (PTSD) checklist-5. Totally, 859 respondents were enrolled, including 544 pregnant women and 315 non-pregnant women. In this study, 5.3%, 6.8%, 2.4%, 2.6%, and 0.9% of pregnant women were identified to have symptoms of depression, anxiety, physical discomfort, insomnia, and PTSD, respectively. However, the corresponding prevalence rates among non-pregnant women were 17.5%, 17.5%, 2.5%, 5.4%, 5.7%, respectively. After adjusting for other covariates, we observed that pregnancy was associated a reduced risk of symptoms of depression (OR = 0.23; 95% CI: 0.12-0.45), anxiety (OR = 0.26; 95% CI: 0.16-0.42), insomnia (OR = 0.19; 95% CI: 0.06-0.58), and PTSD (OR = 0.15; 95% CI: 0.04-0.53) during the COVID-19 epidemic. Our results indicate that during the COVID-19 epidemic in China, pregnant women have an advantage of facing mental problems caused by COVID-19, showing fewer depression, anxiety, insomnia, and PTSD symptoms than non-pregnant women.
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http://dx.doi.org/10.1038/s41398-020-01006-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501755PMC
September 2020

The prevalence of psychiatric symptoms of pregnant and non-pregnant women during the COVID-19 epidemic.

Transl Psychiatry 2020 09 19;10(1):319. Epub 2020 Sep 19.

CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.

Coronavirus disease 2019 (COVID-19) is rapidly spreading worldwide, with a staggering number of cases and deaths. However, available data on the psychological impacts of COVID-19 on pregnant women are limited. The purposes of this study were to assess the prevalence of psychiatric symptoms among pregnant women, and to compare them with non-pregnant women. From February 28 to March 12, 2020, a cross-sectional study of pregnant and non-pregnant women was performed in China. The online questionnaire was used to collect information of participants. The mental health status was assessed by patient health questionnaire, generalized anxiety disorder scale, insomnia severity index, somatization subscale of the symptom checklist 90, and post-traumatic stress disorder (PTSD) checklist-5. Totally, 859 respondents were enrolled, including 544 pregnant women and 315 non-pregnant women. In this study, 5.3%, 6.8%, 2.4%, 2.6%, and 0.9% of pregnant women were identified to have symptoms of depression, anxiety, physical discomfort, insomnia, and PTSD, respectively. However, the corresponding prevalence rates among non-pregnant women were 17.5%, 17.5%, 2.5%, 5.4%, 5.7%, respectively. After adjusting for other covariates, we observed that pregnancy was associated a reduced risk of symptoms of depression (OR = 0.23; 95% CI: 0.12-0.45), anxiety (OR = 0.26; 95% CI: 0.16-0.42), insomnia (OR = 0.19; 95% CI: 0.06-0.58), and PTSD (OR = 0.15; 95% CI: 0.04-0.53) during the COVID-19 epidemic. Our results indicate that during the COVID-19 epidemic in China, pregnant women have an advantage of facing mental problems caused by COVID-19, showing fewer depression, anxiety, insomnia, and PTSD symptoms than non-pregnant women.
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http://dx.doi.org/10.1038/s41398-020-01006-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501755PMC
September 2020

The interaction of ASAH1 and NGF gene involving in neurotrophin signaling pathway contributes to schizophrenia susceptibility and psychopathology.

Prog Neuropsychopharmacol Biol Psychiatry 2021 01 19;104:110015. Epub 2020 Jun 19.

Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Psychotic Disorders, Shanghai, China; Key Laboratory of Translational Psychiatry, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, China. Electronic address:

The neurodevelopmental hypothesis of schizophrenia has been widely accepted. In light of our previous microarray data, two neurodevelopment-related genes were focused on inclduing the N-acylsphingosine amidohydrolase 1 gene (ASAH1) and the nerve growth factor gene (NGF). The evidence that ASAH1 and NGF are associated with schizophrenia is far from conclusive. Furthermore, their interactions in schizophrenia have not been investigated. Total 413 patients and 578 controls were included. Eleven single-nucleotide polymorphisms (SNPs) in ASAH1 and NGF were selected. A multifactor dimensionality reduction (MDR) was applied to investigate gene-gene interactions in schizophrenia, and the traditional odds ratio methods was applied to validate it. The effects of ASAH1, NGF and their interaction on the severity of the disease were analyzed by 3 × 3 covariance analysis of (ANCOVA). The biological interaction between ASAH1 and NGF was examined. KEGG was used to identify the related signaling pathways. After correction by Bonferroni, there were no differences in the genotypic, allelic, or haplotypic frequencies of 11 SNPs between patients and controls. However, the interaction of certain SNPs had effect on susceptibility to schizophrenia, including two high-risk and one low-risk genotypic combinations (OR = 1.49 [1.11-2.00]; OR = 1.45 [1.09-1.92], and OR = 0.64 [0.41-0.98]). ASAH1-rs7830490 and its interaction with NGF-rs4332358 were associated with the general psychopathological subscale score (F  = 3.94, p  = 0.01; F  = 2.36, p  = 0.03). We also found that ASAH1 and NGF interacted with CaMK2B involving in the neurotrophin signaling pathway. Our results suggest that the interaction of ASAH1 and NGF with CaMK2B involved in neurotrophin signaling pathway may contribute to schizophrenia susceptibility and psychopathology.
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http://dx.doi.org/10.1016/j.pnpbp.2020.110015DOI Listing
January 2021

Sex difference in cognitive impairment in drug-free schizophrenia: Association with miR-195 levels.

Psychoneuroendocrinology 2020 09 7;119:104748. Epub 2020 Jun 7.

Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:

Objective: There is evidence that microRNA-195 (miR-195) is associated with schizophrenia (SZ) and cognition, but the relationship between miR-195 and cognitive impairment in SZ is still unknown. Sex differences in both microRNA (miRNA) expression and cognition were found in SZ. We aim to investigate whether sex moderates the relationship between miR-195 levels and cognition in SZ.

Methods: We recruited 121 drug-free SZ patients and 129 healthy controls. miR-195 expression levels in peripheral blood mononuclear cells (PBMCs) were measured using qRT-PCR. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was performed to assess cognitive function. MANCOVA, ANCOVA, correlation analysis and hierarchical linear regression analysis were used to test the effect of sex on the aforementioned variables.

Results: All RBANS scores significantly decreased in patients compared to healthy controls (all p < 0.001); ANCOVA analysis demonstrated female SZ patients had lower delayed memory score (F = 15.36, p < 0.001) and total score (F = 5.26, p = 0.024) than male patients. There was no diagnosis, sex or sex by diagnosis interaction effect on miR-195 levels (all p > 0.05). Interestingly, correlation analysis showed significant negative association between miR-195 and attention score (r = -0.389, p = 0.019), delayed memory score (r= -0.351, p = 0.036), and total score (r = -0.386, p = 0.020) only in female patients. Hierarchical regression analysis showed sex by miR-195 interaction was a significant predictor of the RBANS total score (ΔR2 = 0.042, F(1, 67) = 4.71, p = 0.033).

Conclusion: Our data indicate that miR-195 is associated with cognitive impairment in female SZ patients, and it may be involved in the underlying mechanism of sex differences in cognitive impairment in SZ.
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http://dx.doi.org/10.1016/j.psyneuen.2020.104748DOI Listing
September 2020

Exposure to low concentration of trifluoromethanesulfonic acid induces the disorders of liver lipid metabolism and gut microbiota in mice.

Chemosphere 2020 Nov 1;258:127255. Epub 2020 Jun 1.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, 310032, China. Electronic address:

Trifluoromethanesulfonic acid (TFMS) is the shortest chain perfluorinated compound. Recently, it has been identified as a persistent and mobile organic chemical with a maximum concentration of 1 μg/L in the environment. However, its toxicological mechanism remains unclear. In this study, to evaluate the liver and intestinal toxicity of TFMS in mammals, male mice were orally exposed to 0, 1, 10 and 100 μg/kg for 12 weeks. Our results showed that TFMS exposure reduced the epididymal fat weight in mice, caused the decrease of serum and liver triglyceride (TG) level and the increase of serum low density lipoprotein (LDL) level. Also, we observed the inflammatory cell infiltration in the liver of mice exposed to 10 μg/kg and 100 μg/kg TFMS, which was coupled with the increased mRNA expression levels of inflammatory factors such as COX2, TNF-α, IL-1β in the liver. In addition, the mRNA expression levels of lipid metabolism-related genes (PPAR-α, ACOX, SCD1, PPAR-γ, etc.) were significantly decreased in the liver of mice after exposure to both doses of TFMS. We also found TFMS exposure caused the imbalance of cecal gut microbiota and change of cecal microbiota diversity. KEGG pathway predictions showed that the exposure of 100 μg/kg TFMS changed the synthesis and degradation of ketone bodies, benzoate degradation and several other metabolic pathways. Our findings indicated that TFMS exposure disturbed the liver lipid metabolism possibly via altering the gut microbiota.
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http://dx.doi.org/10.1016/j.chemosphere.2020.127255DOI Listing
November 2020

Interrelationships Between BDNF, Superoxide Dismutase, and Cognitive Impairment in Drug-Naive First-Episode Patients With Schizophrenia.

Schizophr Bull 2020 12;46(6):1498-1510

CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.

The pathogenesis and etiology of schizophrenia (SCZ) remains unclear. Accumulating studies showed that complex interrelationships between brain-derived neurotrophic factor (BDNF) and an imbalanced redox system has a crucial role in the psychopathology of SCZ. However, the influence of the interrelationships of BDNF and superoxide dismutase (SOD) on cognitive impairment and clinical symptomatology in drug-naive first-episode (DNFE) SCZ patients has not been studied thoroughly. Serum BDNF levels, plasma total SOD, manganese-SOD (Mn-SOD), copper/zinc-containing SOD (CuZn-SOD) activities, and malondialdehyde (MDA) levels were measured in 327 DNFE patients with SCZ and 391 healthy controls. Cognitive functions were measured using the Repeatable Battery for the Assessment of Neuropsychological status (RBANS) and clinical symptoms were evaluated by the Positive and Negative Syndrome Scale (PANSS). Compared with the controls, the DNFE patients had increased activities of total SOD and CuZn-SOD, and reduced levels of BDNF and MDA. BDNF levels were positively correlated with CuZn-SOD activity in patients. In addition, we found that elevated Mn-SOD and CuZn-SOD activities were related to PANSS depression factor. Moreover, an interactive effect of BDNF levels and Mn-SOD activity was associated with attentional index score in the patients. Therefore, our findings suggested that interrelationships between BDNF and antioxidant mechanisms might underlie the pathological mechanisms of cognitive impairments and symptomatology in the DNFE patients with SCZ.
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http://dx.doi.org/10.1093/schbul/sbaa062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707068PMC
December 2020

Letter to the Editor "A longitudinal study on the mental health of general population during the COVID-19 epidemic in China".

Brain Behav Immun 2020 07 6;87:132-133. Epub 2020 May 6.

CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, 16 Lincui Road, Chaoyang, Beijing 100101, China. Electronic address:

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http://dx.doi.org/10.1016/j.bbi.2020.05.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201232PMC
July 2020

Neuregulin 3 rs10748842 polymorphism contributes to the effect of body mass index on cognitive impairment in patients with schizophrenia.

Transl Psychiatry 2020 02 11;10(1):62. Epub 2020 Feb 11.

CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.

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 (β = 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: β = 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.
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http://dx.doi.org/10.1038/s41398-020-0746-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026092PMC
February 2020

Depression-like behaviors are accompanied by disrupted mitochondrial energy metabolism in chronic corticosterone-induced mice.

J Steroid Biochem Mol Biol 2020 06 8;200:105607. Epub 2020 Feb 8.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, 310032, China. Electronic address:

Stress exerts its negative effects by interference with mitochondrial energy production in rodents, and is able to impair mitochondrial bioenergetics. However, the underlying mechanism that stress hormone impacts depression-like behaviors and mitochondrial energy metabolism is still not well understood. Here, we investigated the changes of depression-like behaviors and mitochondrial energy metabolism induced by chronic corticosterone (CORT). The results showed that after treatment with CORT for 6 weeks, mice displayed depression-like behaviors, which were identified by tail suspension test, forced swimming test and open field test. Then, the livers were isolated and tested by RNA sequencing and metabolome analysis. RNA sequencing showed 354 up-regulated genes and 284 down-regulated genes, and metabolome analysis revealed 280 metabolites with increased abundances and 193 metabolites with reduced abundances in the liver of mice after CORT, which were closely associated with lipid metabolism and oxidative phosphorylation in mitochondria. Based on these findings, the changes of mitochondrial energy metabolism were investigated, and we revealed that CORT condition inhibited glycolysis and fatty acid degradation pathway, and activated synthesis of triacylglycerol, leading to the reduced levels of acetyl-CoA and attenuated TCA cycle. Also, the pathways of NAD synthesis were inhibited, resulting in the reduced activity of sirtuin 3 (SIRT3). Thus, all of these observations disrupted the function of mitochondria, and led to the decrease of ATP production. Our findings uncover a novel mechanism of stress on depression-like behaviors and mitochondrial energy metabolism in rodents.
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http://dx.doi.org/10.1016/j.jsbmb.2020.105607DOI Listing
June 2020

Interaction between TNF-α and oxidative stress status in first-episode drug-naïve schizophrenia.

Psychoneuroendocrinology 2020 04 30;114:104595. Epub 2020 Jan 30.

The First Clinical Medical College, Nanjing Medical University, Nanjing, China; Department of Neurology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, China. Electronic address:

There has been evidence that the disturbances of TNF-α and the oxidative stress (OxS) status are involved in the mechanism of schizophrenia. However, the results of their levels in schizophrenia are still controversial, and their interactions have not yet been examined, especially in first-episode drug-naïve (FEDN) patients. We therefore applied Enzyme-linked immunosorbent assays (ELISAs) method to compare peripheral blood serum TNF-α, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and malondialdehyde (MDA) levels in 119 FEDN patients with schizophrenia and 135 healthy controls. We found that TNF-α and MDA were higher, whereas GSH-Px was lower, in FEDN patients with schizophrenia compared to healthy controls (TNF-α, 2.21 ± 0.33 vs. 2.11 ± 0.36, Bonferroni p = 0.04; MDA, 2.95 ± 0.87 vs. 2.68 ± 0.76, Bonferroni p = 0.04, GSH-Px, 177.33 ± 28.84 vs. 188.32 ± 29.34, Bonferroni p = 0.03). Furthermore, TNF-α levels had an independent positive association with negative symptoms (r = 0.37, Bonferroni p < 0.001). Finally, GSH-Px levels were negatively associated with the presence of schizophrenia (B =-0.014, Wald statistic = 9.22, p = 0.002, 95 %CI = 0.97-0.99), while the interaction of TNF-α with MDA was a risk factor for schizophrenia (B = 0.22, Wald statistic = 10.06, p = 0.002, 95 %CI = 1.09-1.43). Our results suggest that TNF-α and disturbance of oxidative stress status as well as their interaction may be involved in the pathophysiology of schizophrenia.
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http://dx.doi.org/10.1016/j.psyneuen.2020.104595DOI Listing
April 2020
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