Effects of notoginsenoside R1 on attenuating depressive behavior induced by chronic stress in rats through induction of PI3K/AKT/NF-κB pathway.

Chronic unpredictable mild stress (CUMS) can cause a series of depressive symptoms in depression patients. Recently, notoginsenoside R1 (NGR1) has been reported to play crucial roles in the anti-inflammatory, antioxidant, and anti-apoptotic. However, the role and mechanisms of NGR1 in improving symptoms of depressive behavior remain unknown. Evaluating and identifying its value and exploring the mechanisms of NGR1 on CUMS-induced depressive behavior were the aims of this study. Here, rats were separated into five different groups and treated with or without different concentrations of the NGR1. Then, the body weight, sucrose preference rate, immobility time, crossing number, rearing number, and grooming number were determined to evaluate the effect of NGR1 on improving the depressive behavior of CUMS rats. Subsequently, the morphology of hippocampal neurons and protein expression of brain-derived neurotrophic factor in each group were examined by hematoxylin and eosin staining and western blot to show the neuroprotective effects of NGR1. Furthermore, the mRNA and protein expression of TNF-α, IL-6, and IL-1ß were also detected by quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay to verify the anti-inflammatory effects of NGR1 on CUMS rats. In addition, the cell apoptosis-related proteins were examined to reveal that NGR1 can inhibit cell apoptosis in CUMS rats. Moreover, it was confirmed that NGR1 attenuated the symptoms of depressive behavior by mediated PI3K/Akt/NF-κB pathway. Together, this study shows that NGR1 improves depressive behavior induced by chronic stress in rats through activation of PI3K/AKT/NF-κB pathway.

Identifying Plasma Biomarkers with high specificity for major depressive disorder: A multi-level proteomics study.

BACKGROUND: There are currently no objective diagnostic biomarkers for major depressive disorder (MDD) due to the biological complexity of the disorder. The existence of blood-based biomarkers with high specificity would be convenient for the clinical diagnosis of MDD. METHODS: A comprehensive plasma proteomic analysis was conducted in a highly homogeneous cohort [7 drug-naïve MDD patients and 7 healthy controls (HCs)], with bioinformatics analysis combined with machine learning used to screen candidate proteins. Verification of reproducibility and specificity was conducted in independent cohorts [60 HCs and 74 MDD, 42 schizophrenia (SZ) and 39 bipolar I disorder (BD-I) drug-naïve patients]. Furthermore, verification of consistency was accomplished by proteomic analysis of postmortem brain tissue from 16 MDD patients and 16 HCs. RESULTS: Levels of C-reactive protein (CRP), antithrombin III (ATIII), inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) and vitamin D-binding protein (VDB) were significantly higher in MDD patients, both in the discovery cohort and independent replication cohort. In comparison with SZ or BD-I patients, two proteins (VDB and ITIH4) were significantly elevated only in MDD patients. In addition, increased VDB and ITIH4 were observed consistently in both plasma and postmortem dorsolateral prefrontal cortex tissues of MDD patients. Furthermore, a panel consisting of all four plasma proteins was able to distinguish MDD patients from HCs or SZ or BD-I patients with the highest accuracy. CONCLUSION: Plasma ITIH4 and VDB may be potential plasma biomarkers of MDD with high specificity. The four-protein panel is more suitable as a potential clinical diagnostic marker for MDD.

Neurocognition and social cognition in remitted first-episode schizophrenia: correlation with VEGF serum levels.

BACKGROUND: Accumulating evidence suggests that serum vascular endothelial growth factor (VEGF) in many neurobiological processes potentially contributes to the pathophysiology of psychiatric disorders, particularly cognitive decline. The purpose of this study was to explore the differences in neurocognition, social cognition and VEGF among remitted first-episode schizophrenic patients, non-remitters and normal control subjects. Moreover, we investigated the association between serum VEGF levels and cognitive functions. METHOD: 65 remission (RS) and 45 nonremission patients (NRS) after first-episode schizophrenia, as well as 58 healthy controls (HC) were enrolled in this study. Social cognition was assessed using the Chinese Facial Emotion Test (CFET); neurocognition was measured with a test battery consisting of Hopkins Verbal Learning Test-Revised, Verbal Fluency Test, Trail Making Tests, Digit Span Tests (DST) and Stroop Tests. Blood samples were collected for VEGF measurements. Data was analyzed with SPSS 22.0 (Chicago, IL, USA). RESULTS: On nearly all neurocognitive tests (except for DST), RS performed significantly worse than HC but better than NRS (P < 0.05). NRS, but not RS, exhibited markedly poorer social cognition than HC (except for Happiness and Surprise subscales of the CFET) (P < 0.05). VEGF levels showed a gradient change among three groups (HC > RS > NRS). CONCLUSION: Compared to HC, RS demonstrated poorer neurocognitive but intact social cognition functioning. These results indicate that VEGF levels decreased gradually with the severity of cognitive impairment in schizophrenia. VEGF may be involved in the pathological mechanism of cognitive performance in RS.

Elevated serum vascular endothelial growth factor in treatment-resistant schizophrenia treated with electroconvulsive therapy: Positive association with therapeutic effects.

OBJECTIVES: As the name implies, vascular endothelial growth factor (VEGF) enhances angiogenesis, promotes vascular permeability, and stimulates neurogenesis in the adult brain. Furthermore, animal model studies have shown that electroconvulsive therapy (ECT), which is primarily utilised in cases of treatment-resistant schizophrenia (TRS), regulates the expression of VEGF. The current study focuses largely on the effect of ECT on VEGF serum concentration, and the relationship between VEGF and therapeutic effects in patients diagnosed with TRS. METHODS: Participants comprised 40 TRS patients and 43 healthy controls. Clinical severity was assessed (i.e. 1 day before commencement of ECT and 1 day following ECT) using the positive and negative syndrome scale (PANSS). Blood samples were also collected for VEGF measurements at corresponding time points. RESULTS: Pre-treatment serum VEGF levels were significantly lower in TRS patients compared to healthy controls. VEGF concentrations increased significantly following ECT, whereas no difference was found in controls. Moreover, there was a positive correlation between the change in VEGF and therapeutic effects. CONCLUSIONS: Elevated serum VEGF in TRS treated with ECT is positively associated with therapeutic effects, suggesting that alterations in VEGF levels may constitute an index by which to evaluate the improvement in clinical condition.

Altered serum levels of glial cell line-derived neurotrophic factor in male chronic schizophrenia patients with tardive dyskinesia.

OBJECTIVES: Many research indicate that the tardive dyskinesia (TD) is generally linked with long-term antipsychotic therapy for schizophrenia. Glial cell line-derived neurotrophic factor (GDNF) is a critical role in the protection of catecholaminergic, dopaminergic, and cholinergic neurons. Thus, we examined the serum GDNF levels in schizophrenia patients with TD (WTD) and without TD (NTD) and compared with healthy controls (HC), respectively. METHODS: Totally 75 males with schizophrenia were recruited into this study. All were measured by the Diagnostic and Statistical Manual of Mental Disorders, fifth edition, the Positive and Negative Syndrome Scale, and the Abnormal Involuntary Movement Scale (AIMS). The patient group was divided into two subgroups: WTD (n = 32) and NTD (n = 43) according to the AIMS score. Fifty-three healthy controls matching in age and gender were also enlisted from the region. GDNF levels were examined with sandwich enzyme-linked immunosorbent assay. RESULTS: Analysis of variance indicated significant differences between the three groups (P = 0.012); GDNF levels in the WTD group were significantly different from those in the NTD (P = 0.030) and HC (P = 0.003) groups. CONCLUSION: Decreased GDNF levels in TD patients indicated that alterations in neurotrophic factors may be involved in the pathophysiology of TD, but the exact mechanisms need further investigation.

Baseline serum vascular endothelial growth factor levels predict treatment response to antipsychotic medication in patients with schizophrenia.

Vascular endothelial growth factor (VEGF) is implicated in angiogenesis, blood flow, and neuroplasticity, which have previously been shown to contribute to schizophrenia and the mechanisms of action of antipsychotic medication. The aim of the present study was to investigate whether baseline serum VEGF levels predict treatment responses to antipsychotic medication. Drug-free adults with schizophrenia were administered monotherapy with atypical antipsychotic drugs for 6 weeks. Participants' psychiatric symptoms were assessed using the positive and negative symptom scale (PANSS) before and after treatment. Blood samples for VEGF measurements were collected from 201 participants comprising 83 healthy controls and 118 patients (i.e. only on admission). Baseline VEGF levels in adults with schizophrenia were significantly lower than those in the control group (t = 3.656, df = 199, P < 0.001). In particular, pretreatment VEGF levels were significantly higher in patients responding to drug treatment at follow-up (≥ 50% reduction in initial PANSS total) (t = 4.743, df = 116, P < 0.001). The predictive power of serum VEGF levels was investigated using receiver operating characteristic curves. The area under the curve was 0.774 (95% confidence interval 0.688-0.846); for fixed specificity of 78.8%, the corresponding sensitivity was 63.5%. Results from this preliminary experiment suggest high baseline serum concentrations of VEGF may predict a better response to antipsychotic medications in adults with schizophrenia. Further studies using larger sample sizes are needed to verify the findings.

Altered serum levels of vascular endothelial growth factor in first-episode drug-naïve and chronic medicated schizophrenia.

There is much evidence of a relationship between alterations in the brain's regional cellular energy metabolism and blood flow in schizophrenic. Vascular endothelial growth factor (VEGF) plays a role in the pathogenesis of neuropsychiatric illnesses. So, we compared serum VEGF levels in drug-naïve first-episode psychotic (FEP) and chronically medicated schizophrenic to examine if a correlation existed between VEGF and psychopathological symptoms. The serum VEGF levels were assessed in 46 FEP patients, 47 chronic medicated patients and 50 healthy controls. Symptoms of schizophrenia were evaluated with the Positive and Negative Syndrome Scale (PANSS) and sandwich enzyme-linked immunosorbent assay (ELISA) was used to measure serum VEGF levels. VEGF levels were significantly lower in FEP patients compared to both chronically medicated schizophrenic patients and healthy controls, while VEGF levels in chronically medicated patients were markedly higher than in healthy controls. Furthermore, a significant correlation was detected between the levels and the PANSS negative subscale among patient groups. However, no significant correlation was observed between VEGF and clinical variables in patients. This study suggested that imbalanced neurotrophic factors may be associated with the onset of schizophrenia, but subsequent increased VEGF may be related to medication or other factors in disease progression.