Adipose-derived mesenchymal stem cells protect against CMS-induced depression-like behaviors in mice via regulating the Nrf2/HO-1 and TLR4/NF-κB signaling pathways.

Increasing studies show that inflammatory processes may be involved in depressive disorders. Nuclear factor erythroid-2 related factor 2 (Nrf2) modulates tissue microglial M1 phenotypic changes to the M2 phenotype, which is implicated in protection against inflammatory diseases. We have reported that the adipose-derived mesenchymal stem cells (ADSCs) display anti-inflammatory activity. In this study we explored whether the mechanism of anti-inflammatory activity of ADSCs was related to Nrf2. ADSCs were isolated from mouse fat pads and intravenously administered to chronic mild stress (CMS)-exposed C57BL/6 mice at the dose of 1 × 106 once a week for 3 weeks. We showed that ADSC administration significantly remedied CMS-induced depressive-like behaviors in sucrose preference test, tail suspension test, and forced swim test accompanied by suppressing microglial activation and the expression of inflammatory factors including MCP-1, TNF-α, IL-1ß, and IL-6. Furthermore, ADSC administration promoted both the expression of BDNF and TrkB, and promoted Nrf2/HO-1 signaling but suppressed TLR4/NF-κB signaling in brain tissue. In order to elucidate the role of Nrf2/HO-1 signaling in ADSC-caused neuroprotection, Nrf2-modified ADSCs were cocultured with BV2 microglial cells, then exposed to lipopolysaccharide (LPS). Downregulation of Nrf2 in ADSCs decreased the protective effects of ADSCs against LPS-induced microglial activation and M1 polarization. Nrf2 overexpression in ADSCs markedly suppressed LPS-induced TLR4 and NF-κB expression in microglial cells. These results suggest a possible antidepressive mechanism correlated with microglial polarization for anti-inflammatory agents, which may provide a new microglia-targeted strategy for depression therapy.

Venlafaxine inhibits apoptosis of hippocampal neurons by up-regulating brain-derived neurotrophic factor in a rat depression model.

The effect of venlafaxine on the expression of brain-derived neurotrophic factor (BDNF) in rat hippocampal neurons was studied, as well as its inhibitory effect on apoptosis of hippocampal neurons. Differences in behavioral ability between the depression model group and the venlafaxine treatment group were observed in behavioral, sucrose-water and open field tests. The rat hippocampal tissue was sliced, stained and observed for BDNF distribution by immunohistochemistry. Apoptosis of hippocampal neurons was detected by TUNEL. BDNF expression in the hippocampal tissue was detected by Western blot. Injury and apoptosis of the hippocampal tissue were observed by electron microscopy. Behavioral test showed that venlafaxine effectively improved the behavioral abilities of depressed rats. Immunohistochemistry showed that venlafaxine markedly increased BDNF expression in the rat hippocampus. TUNEL showed that venlafaxine markedly inhibited apoptosis of hippocampal neurons, which was also confirmed by electron microscopic observation of the pathologic sections. Venlafaxine improved the expression of BDNF by influencing the PI3k/PKB/eNOS pathway and repressed the apoptosis of hippocampal neurons.

Clinical evaluation of the efficacy and safety of tandospirone versus sertraline monotherapy for social anxiety disorder: a randomized open-label trial.

OBJECTIVE: Although selective serotonin reuptake inhibitors are now established as first-line pharmacotherapy for social anxiety disorder (SAD), other agents with different mechanisms have shown promise in treating SAD. The aim of this study was to examine the efficacy and safety of tandospirone in treating adolescents with SAD. METHODS: Adolescent patients meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for SAD were randomly assigned (1:1) to open-label treatment with either tandospirone or sertraline for 8 weeks. The primary outcome measures were changes from baseline in the Hamilton Anxiety (HAM-A) scale and response using the Clinical Global Impression of Improvement (CGI-I) scale. RESULTS: The adjusted mean change in HAM-A scores from baseline was indicating a significant improvement over baseline in both treatment arms (p < 0.0001). The mean CGI-I scale score at week was with no significant difference between the two arms (p = 0.42). Rates of response were 48.6% for tandospirone and 55.6% for sertraline using the CGI-I. Response rates were 37.1% for tandospirone and 41.7% for sertraline using a HAM-A response criterion (≥50% reduction). The adjusted mean change in Social Phobia Inventory scores from baseline was indicating a significant improvement over baseline in both treatment arms (p < 0.0001). CONCLUSIONS: Tandospirone is safe and effective and appears non-inferior to sertraline for SAD in youths.

Early outcomes, associated factors and predictive values of clinical outcomes of tandospirone in generalized anxiety disorder: a post-hoc analysis of a randomized, controlled, multicenter clinical trial.

OBJECTIVE: To examine the early outcomes, associated factors and predictive values of clinical outcomes of different tandospirone doses in patients with a generalized anxiety disorder (GAD). METHODS: This was a posthoc analysis of "a randomized, controlled multicenter clinical trial of the efficacy and safety of different doses of tandospirone on GAD". A total of 274 patients with GAD were included and randomized into the high-dose (tandospirone 60 mg/d) and low-dose (tandospirone 30 mg/d) groups for a 6-week treatment. The Hamilton Anxiety (HAMA), Clinical Global Impression-Severity (CGI-S), Short-Form-12 (SF-12) scales were used for assessment. The trial was registered at clinical trail.gov (NCT01614041). RESULTS: (1) In the first week of treatment, 35.8% of patients in the high-dose group fulfilled the early onset criteria, which was significantly higher than 19.0% found in the low-dose group (p = 0.002). In the second week of treatment, 22.6% of patients in the high-dose group achieved an early response, versus 12.4% in the low-dose group, indicating a significant difference (p = .026). (2) Factors associated with early onset at week 1 included baseline HAMA total score (OR = 0.916, 95%CI 0.882-0.952), age (OR = 0.974, 95%CI 0.950-0.998), drug dose (30 mg vs. 60 mg; OR = 0.298, 95%CI 0.156-0.568) and SF-12 physiological total score (OR = 1.030, 95%CI 1.010-1.050). (3) Early onset was significantly associated with response rate (OR = 18.34, 95%CI 12.10-27.81), remarkable response rate (OR = 27.56, 95%CI 11.65-65.17) and recovery rate (OR = 11.85, 95%CI 4.98-28.18). Group (high dose group vs. low dose group) (χ2 = 8.535, p = .003) and baseline HAMA total score (χ2 = 70.840, p < .001) were independent predictors of onset time. CONCLUSIONS: The early outcomes of high-dose tandospirone in the treatment of GAD are better than those of the low-dose group. Patients with younger age at onset, milder anxiety symptoms and better physiological functions administered high-dose tandospirone showed rapid onset, great early outcomes, high recovery rate and good prognosis. Drug onset time had a good predictive effect on treatment outcome.

Difference in proinflammatory cytokines produced by monocytes between patients with major depressive disorder and healthy controls.

BACKGROUND: Immune activation and suppression in patients with major depressive disorders (MDD) have been both reported in different studies. We assume that these findings may indicate innate immunological tolerance in MDD, with subclinical elevated level of proinflammatory cytokines and the decrease in innate immune response while encountering pathogens. METHODS: Peripheral monocytes of 50 untreated patients with MDD and 40 healthy controls were isolated and cultured, with or without 10 ng/ml lipopolysacchride (LPS) for 6 h (6 h, LPS+/-), and with LPS for 18 h (18, LPS+). The cell culture supernatants were collected to measure concentrations of tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and interleukin 1 beta (IL-1ß). RESULTS: The baseline concentrations of IL-6 and IL-1ß (6 h, LPS-) were significantly higher in the MDD group than those in the control group. There was no significant difference of TNF-α between the two groups. The fold changes of LPS-induced secretion of IL-6 and TNF-α from monocytes cultured for 6 and 18 h were all lower in the patient groups, and that was true for IL-1ß as monocytes cultured for 18 h. LIMITATIONS: Given the gap between the results of in vitro experiments and the actual response that happens in vivo when the immune system encounters pathogens from the external world, future research should include in vivo methods to test the results of the current study. CONCLUSIONS: Patients with MDD may have subclinical inflammation during a depressive episode, and the reduced response to LPS in monocytes indicates innate immunological tolerance.

[Effects of paroxetine with or without zolpidem on depression with insomnia: a multi-center randomized comparative study].

OBJECTIVE: To compare the effects of paroxetine with or without zolpidem on depression with insomnia. METHODS: 229 consecutive outpatients with the diagnosis of major depression based on the CCMD-3 criteria who visited the departments of mental counseling, psychiatric, or neurology in 11 general hospitals the country over during a period of 4 weeks, were randomly allocated into 2 groups: paroxetine + zolpidem group (Group A, treated with paroxetine 10 - 20 mg/d and zolpidem 10 mg/d H. d. for 4 weeks) and paroxetine group (Group B, treated with paroxetine only), among which 221 underwent intention-to-treat analysis and 207 underwent completer analysis (CA). Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale-17 (HAMD-17), Pittsburg sleep quality index (PSQI), and 36-item Short Form Health Survey (SF-36) were used to evaluate the outcomes. RESULTS: One week after the beginning of treatment the reduction of PSQI score of Group A was 5.7, showing an improvement of sleep quality, significantly higher than that of Group B (1.6), and 4 weeks later the reduction of PSQI of Group A was 9.7 +/- 3.6, significantly higher than that of Group B (6.0 +/- 3.5, both P = 0.000). Four weeks after the beginning of treatment, the HAMD reduction rate of Group A was 68.5%, significantly higher than that of Group B (56.8%, P < 0.01), and the HAMA reduction rate of Group A was 66.2%, significantly higher than that of Group B (57.1%, P < 0.01), and the SF-36 score of Group A was 66 +/- 19 (last observation carry forward analysis) or 67 +/- 19 (CA), significantly higher than those of Group B (38 +/- 16 or 67 +/- 19 respectively, both P = 0.000). CONCLUSION: selective serotonin reuptake inhibitor antidepressant combined with hypnotic augments the effects of antidepressant on the depressive and anxiety symptoms.

The link between long noncoding RNAs and depression.

The major depressive disorder (MDD) is a relatively common mental disorder from which that hundreds of million people have suffered, leading to displeasing life quality, which is characterized by health damage and even suicidal thoughts. The complicated development and functioning of MDD is still under exploration. Long noncoding RNA (lncRNAs) are highly expressed in the brain, could affect neural stem cell maintenance, neurogenesis and gliogenesis, brain patterning, synaptic and stress responses, and neural plasticity. The dysregulation of certain lncRNAs induces in neurodevelopmental, neurodegenerative and neuroimmunological disorders, primary brain tumors, and psychiatric diseases. Although advances have been made, no fully satisfactory treatments for major depression are available, further investigation is requested. And recently data showed that the expression level of the majority of lncRNAs demonstrated a clear tendency of upregulation, and the certain dysregulated miRNAs and lncRNAs in the MDD have been proved to have a co-synergism mechanism, that is why we speculate lncRNA might get the capability to regulate MDD. Few identified lncRNAs have been deeply studied in detailed experiments up until now, little predictions of their function have been raised, and further researches is calling for discover their signal pathway and related regulatory networks.

[A study of mental health issues in the objects of substance abstinence who got labor education and rehabilitation].

OBJECTIVE: To investigate the personality and mental health of the objects of substance (caffeine, cocaine, hallucinogens and so on) abstinence who got labor education and rehabilitation. METHODS: 258 male objects and 250 female objects of substance abstinence selected randomly from institutions of labor education and rehabilitation were assessed with MMPI and SCL-90. RESULTS: MMPI tests indicated the personality abnormality in the objects. SCL-90 tests manifested the mental health abnormality of them compared with Chinese models, especially in the female objects. CONCLUSION: More attention should be paid on the mental health of the objects of substance abstinence.

Venlafaxine inhibits apoptosis of hippocampal neurons by up-regulating brain-derived neurotrophic factor in a rat depression model.

OBJECTIVE: To study the effect of venlafaxine on the expression of brain-derived neurotrophic factor (BDNF) in rat hippocampal neurons, as well as its inhibitory effect on apoptosis of hippocampal neurons. METHODS: Differences in behavioral ability between the depression model group and the Venlafaxine treatment group were observed using behavioral, sucrose-water and open field tests. The rat hippocampal tissue was sliced, stained and observed for BDNF distribution by immunohistochemistry. Apoptosis of hippocampal neurons was detected by TUNEL. BDNF expression in the hippocampal tissue was detected by Western blot. Injury and apoptosis of the hippocampal tissue were observed by electron microscopy. RESULTS: Behavioral test showed that venlafaxine effectively improved the behavioral abilities of depressed rats. Immunohistochemistry showed that venlafaxine markedly increased the BDNF expression in the rat hippocampus. TUNEL showed that venlafaxine markedly inhibited apoptosis of hippocampal neurons, which was also confirmed by electron microscopic observation of the pathologic sections. CONCLUSION: Venlafaxine improved the expression of BDNF through working on PI3k/PKB/eNOS pathway and repressed the apoptosis of hippocampal neurons.

Efficacy of venlafaxine extended-release monotherapy for first-episode depression with painful physical symptoms.

Pain is the most common symptom reported in both the general population and the general medical setting. The aim of this study is to evaluate the effectiveness, tolerance, and safety of venlafaxine extended-release (XR) monotherapy in treating first-episode outpatients fulfilling the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) criteria for major depressive disorder with associated painful physical symptoms. Of the 102 outpatients enrolled, 86 (84.3%) completed the study. Venlafaxine XR treatment (75-225 mg/day) was followed by a significant decrease in the total scores for the 17-item Hamilton Depression Rating Scale from baseline to the second weekend (t value=16.12, P<0.0001) and at every subsequent visit (weeks 4, 6, and 8, all P<0.0001). Significant differences were also found in the mean Visual Analog Scales for overall pain and the mean medical outcomes study pain measures from baseline to the second weekend (t value=14.99, P<0.0001; t value=12.59, P<0.0001) and at every visit (all P<0.0001). At the end of the eighth week, venlafaxine XR achieved response and remission rates of 68.6 and 40.2%, respectively. The remission rate for pain responders (improvement in Visual Analog Scale overall pain from baseline to last observation ≥50%) was significantly greater than that for pain nonresponders (56.1 vs. 20.0%, P<0.0001). The most common (≥10%) adverse events were nausea (31.4%), dizziness (26.5%), and somnolence (22.5%). Venlafaxine XR is possibly an effective and safe option in the treatment of depression and associated painful physical symptoms.