Adverse childhood experience and depression: the role of gut microbiota.

Depression is the most common psychiatric disorder that burdens modern society heavily. Numerous studies have shown that adverse childhood experiences can increase susceptibility to depression, and depression with adverse childhood experiences has specific clinical-biological features. However, the specific neurobiological mechanisms are not yet precise. Recent studies suggest that the gut microbiota can influence brain function and behavior associated with depression through the "microbe-gut-brain axis" and that the composition and function of the gut microbiota are influenced by early stress. These studies offer a possibility that gut microbiota mediates the relationship between adverse childhood experiences and depression. However, few studies directly link adverse childhood experiences, gut microbiota, and depression. This article reviews recent studies on the relationship among adverse childhood experiences, gut microbiota, and depression, intending to provide insights for new research.

People with passive sleep delay have more severe depression and sleep problems than those with active sleep delays-a cross-sectional study after the COVID-19 pandemic.

Objective: This study was designed to investigate the effect of different types of sleep delay in depression and sleep characteristics after the pandemic. Meanwhile, risk factors for depression were also explored. Methods: The survey was conducted in Wuhan from March 1 to May 30, 2021, and participants were recruited through a snowball process. A total of 1,583 people with sleep delays responded to the invitation, of which 1,296 were enrolled. Participants filled out a questionnaire including social demographics, sleep characteristics, Social Support Rating Scale (SSRS), Pittsburgh Sleep Quality Index (PSQI) and Patient Health Questionnaire-9 (PHQ-9). Results: There were no significant differences in sex, social support and level of education between the two types of sleep delay (p = 0.961, p = 0.110, p = 0.090), but the average age of the passive sleep delay group was higher (p = 0.015). And most people with active sleep delay were caused by the use of electronic devices (73.6%), while most people with passive sleep delay were caused by work or study tasks (73.2%), with a significant difference between the two groups (p < 0.001). People who actively delayed sleep had more regular sleep (p < 0.001), better sleep quality and longer sleep duration (p < 0.001, p < 0.001). In addition, although they delayed sleep more frequently (p < 0.001), they had significantly lower depression degree than people who passively delayed sleep (p < 0.001). Conclusions: Passive sleep delays, usually caused by work or study, has higher levels of depression and more adverse sleep behaviors than active sleep delay. The findings help further understand the effects of delayed sleep and provide insight for people with delayed sleep to evaluate their own condition. Future studies are required to standardize and accurately classify sleep delay and further explore it.

Nightmares mediate the association between traumatic event exposure and suicidal ideation in frontline medical workers exposed to COVID-19.

BACKGROUND: Trauma experience increases the risk of suicidal ideation, but little is known about potentially psychological mechanisms underlying this relationship. This study aims to examine the relationship between coronavirus disease 2019 (COVID-19)-related traumatic event (CTE) exposure and suicidal ideation among hospital workers, and identify mediating roles of sleep disturbances in this relationship. METHODS: Workers in seven designated hospitals in Wuhan, China, were invited to participate in an online survey from May 27, 2020, to July 31, 2020. Participants completed a self-report questionnaire to evaluate demographic characteristics, level of CTE exposures, nightmare frequency, insomnia severity, symptoms of depression and anxiety, and suicidal ideation. A series of correlation analyses were performed, and a mediation model was generated to examine correlations between CTE exposure, sleep disturbances, and suicidal ideation. RESULTS: A total of 16,220 hospital workers were included in the final analysis, 13.3% of them reported suicidal ideation in the past month. CTE exposure was significantly associated with insomnia severity, nightmare frequency, and suicidal ideation. After controlling potential confounders, nightmares but not insomnia, depression, or anxiety were shown to be independent risk factors for suicidal ideation. Pathway analyses showed that the relationship between CTE exposure and suicidal ideation was fully mediated by nightmares (proportion mediated 66.4%) after adjusting for demographic characteristics and psychological confounders. LIMITATIONS: Cross-sectional design precluded the investigation of causal relationships. CONCLUSIONS: CTE exposure increases risk of hospital workers' suicidal ideation that is mediated by nightmares, suggesting nightmares intervention might be considered as a component when developing suicide prevention strategies.

RGFP966 is protective against lipopolysaccharide-induced depressive-like behaviors in mice by inhibiting neuroinflammation and microglial activation.

Depression is a prevalent mental disorder. However, its pathophysiological mechanism has still remained elusive, and a limited number of effective treatments have been presented. Recent studies have shown that neuroinflammation and microglial activation are involved in the pathogenesis of depression. Histone deacetylase 3 (HDAC3) has neurotoxic effects on several neuropathological conditions. The inhibition of HDAC3 has been reported to induce anti-inflammatory and antioxidant effects. RGFP966 is a highly selective inhibitor of HDAC3. This study aimed to investigate the antidepressant effect of RGFP966 on lipopolysaccharide (LPS)-induced depressive-like behaviors in mice and to explore its possible mechanism. Adult male C57BL/6J mice were utilized in this study. The LPS and RGFP966 were injected intraperitoneally daily for 5 days. The behavior tests were performed to elucidate the depression-like behaviors. Western blot, ELISA and immunofluorescence staining were used to study the HDAC3/TLR4/NLRP3 pathway-related proteins. The results of behavioral tests showed that RGFP966 could improve the LPS-induced depressive-like behaviors in mice. The results of Western blotting showed that RGFP966 treatment downregulated the expression levels of toll-like receptor 4 (TLR4), nucleotide-binding oligomerization domain-like receptor pyrin domain-containing-3 (NLRP3), caspase-1, and interleukin-1ß (IL-1ß) (P < 0.05). Furthermore, the results of immunofluorescence staining showed that RGFP966 treatment inhibited microglial activation in the hippocampus of mice (P < 0.01). These findings suggested that RGFP966 could effectively ameliorate LPS-induced depressive-like behaviors in mice by inhibiting neuroinflammation and microglial activation. The anti-inflammatory mechanism of RGFP966 might be related to the inhibition of the HDAC3/TLR4/NLRP3 signaling pathway. Therefore, inhibition of HDAC3 using RGFP966 could serve as a potential treatment strategy for depression.

Neuropsychiatric manifestations of COVID-19, potential neurotropic mechanisms, and therapeutic interventions.

The coronavirus disease 2019 (COVID-19) pandemic has caused large-scale economic and social losses and worldwide deaths. Although most COVID-19 patients have initially complained of respiratory insufficiency, the presence of neuropsychiatric manifestations is also reported frequently, ranging from headache, hyposmia/anosmia, and neuromuscular dysfunction to stroke, seizure, encephalopathy, altered mental status, and psychiatric disorders, both in the acute phase and in the long term. These neuropsychiatric complications have emerged as a potential indicator of worsened clinical outcomes and poor prognosis, thus contributing to mortality in COVID-19 patients. Their etiology remains largely unclear and probably involves multiple neuroinvasive pathways. Here, we summarize recent animal and human studies for neurotrophic properties of severe acute respiratory syndrome coronavirus (SARS-CoV-2) and elucidate potential neuropathogenic mechanisms involved in the viral invasion of the central nervous system as a cause for brain damage and neurological impairments. We then discuss the potential therapeutic strategy for intervening and preventing neuropsychiatric complications associated with SARS-CoV-2 infection. Time-series monitoring of clinical-neurochemical-radiological progress of neuropsychiatric and neuroimmune complications need implementation in individuals exposed to SARS-CoV-2. The development of a screening, intervention, and therapeutic framework to prevent and reduce neuropsychiatric sequela is urgently needed and crucial for the short- and long-term recovery of COVID-19 patients.

Scutellarin protects against lipopolysaccharide-induced behavioral deficits by inhibiting neuroinflammation and microglia activation in rats.

Depression is a complex and heterogeneous mental disorder. Yet, the mechanisms behind depression remain elusive. Increasing evidence suggests that inflammatory reaction and microglia activation are involved in the pathogenesis of depression. Scutellarin has been found to have anti-inflammatory and antioxidant effects in various diseases. The aim of the present study was to investigate the anti-depressant effects and potential mechanism of scutellarin in the lipopolysaccharide (LPS)-induced depression animal model. The behavioral tests showed that scutellarin administration ameliorated LPS-induced depressive-like behaviors. Additionally, the scutellarin treatment inhibited reactive oxygen species (ROS) generation. Western blot analysis results showed that scutellarin pretreatment suppressed LPS-induced the protein levels of NLRP3, caspase-1, and IL-1ß. Furthermore, immunostaining results showed that scutellarin pretreatment inhibited LPS-induced microglia activation in the hippocampus of rats. These findings suggest that scutellarin effectively improves LPS-induced inflammation-related depressive-like behaviors by inhibiting LPS-induced neuroinflammation and microglia activation, possibly via regulation of the ROS/NLRP3 signaling pathway and microglia activation. Thus, scutellarin may serve as a potential therapeutic strategy for depression.

Abnormal Local Activity and Functional Dysconnectivity in Patients with Schizophrenia Having Auditory Verbal Hallucinations.

Auditory verbal hallucination (AVH) is emphasized as a pathological hallmark of schizophrenia. Neuroimaging studies provide evidence linking AVH to overlapping functional abnormalities in distributed networks. However, no clear conclusion has still been reached. This study aimed to further explore the brain activity of patients with schizophrenia having AVH from both local activity (LA) and functional connectivity (FC) insights, while excluding confounding factors from other positive symptoms. A total of 42 patients with AVH (AVH patients group, APG), 26 without AVH (non-AVH patients group, NPG), and 82 normal controls (NC) underwent resting-state functional magnetic resonance imaging (fMRI). LA measures, including regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuations (fALFF), and FC measures were evaluated to understand the neuroimaging mechanism of AVH. APG showed increased ReHo and fALFF in the bilateral putamen (Put) compared with NPG and NC. FC analysis (using bilateral putamen as seeds) revealed that all patients showed abnormal FC of multiple resting-state network regions, including the anterior and post cingulate cortex, middle frontal gyrus, inferior parietal gyrus, and left angular gyrus. Interestingly, APG showed significantly decreased FC of insula extending to the superior temporal gyrus and inferior frontal gyrus compared with NPG and NC. The present findings suggested a significant correlation of abnormal LA and dysfunctional putamen-auditory cortical connectivity with the neuropathological mechanism of AVH, providing evidence for the functional disconnection hypothesis of schizophrenia.

Silencing of long non-coding RNA CRNDE promotes autophagy and alleviates neonatal hypoxic-ischemic brain damage in rats.

Hypoxic-ischemic (HI) brain damage (HIBD) leads to high neonatal mortality and severe neurologic morbidity. Autophagy is involved in the pathogenesis of HIBD. This study aims to investigate the effect of long non-coding RNA colorectal neoplasia differentially expressed (CRNDE) on HIBD and to validate whether autophagy is involved in this process. A HIBD model in rat pups and a HI model in rat primary cerebrocortical neurons were established. Autophagy was evaluated by western blot. The HIBD in rats was evaluated by hematoxylin and eosin staining, TUNEL staining, triphenyl tetrazolium chloride staining, and morris water maze test. The HI injury in vitro was evaluated by determining cell viability and apoptosis. The results showed that CRNDE expression was time-dependently increased in the brain after HIBD. Administration with CRNDE shRNA-expressing lentiviruses alleviated pathological injury and apoptosis in rat hippocampus, decreased infarct volume, and improved behavior performance of rats subjected to HIBD. Furthermore, CRNDE silencing promoted cell viability and inhibited cell apoptosis in neurons exposed to HI. Moreover, CRNDE silencing promoted autophagy and the autophagy inhibitor 3-methyladenine counteracted the neuroprotective effect of CRNDE silencing on HI-induced neuronal injury both in vivo and in vitro. Collectively, CRNDE silencing alleviates HIBD, at least partially, through promoting autophagy.

Long non-coding RNA CRNDE deteriorates intrauterine infection-induced neonatal brain injury.

BACKGROUND: This study aimed to test the hypothesis that long non-coding RNA (lncRNA) colorectal neoplasia differentially expressed (CRNDE) could exacerbate brain injury caused by intrauterine infection in neonatal rats. METHODS: Intrauterine infection was induced in pregnant rats by lipopolysaccharide (LPS). After delivery, newborn rats with brain injury caused by intrauterine infection were randomly divided into control, control shRNA, and CRNDE shRNA groups. CRNDE expression in serum and amniotic fluid of pregnant rats and neonatal brain tissues were determined by quantitative real-time PCR (qRT-PCR). Morris water maze (MWM) task was used to test the spatial learning and memory ability. Histological examination and apoptosis detection were performed by hematoxylin and eosin (H&E) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, respectively. Immunohistochemistry was conducted to evaluate the activation of astrocytes and microglia. RESULTS: LncRNA CRNDE was highly expressed in serum and amniotic fluid of maternal rats and in brain tissues of offspring rats. Furthermore, shRNA-mediated CRNDE downregulation could rescue the spatial learning and memory ability, improve brain histopathological changes and cell death, and inhibit the activation of astrocytes and microglia caused by LPS. CONCLUSION: CRNDE silencing possessed a cerebral protective effect in neonatal rats with brain injury caused by interauterine infection.

Efficacy and safety of lurasidone versus placebo as adjunctive to mood stabilizers in bipolar I depression: A meta-analysis.

BACKGROUND: Few evidence-based treatments and guidelines reflect greater uncertainty regarding consensus treatment algorithms than those for unipolar disorder. This meta-analysis aimed to evaluate the efficacy and side effects of lurasidone by comparing with placebo in bipolar I depression. METHODS: Electronic databases, such as PubMed, the Cochrane Library, Web of Science, and Embase, were searched until May 30, 2018, for randomized controlled trials on comparison lurasidone therapy with placebo. The primary efficacy assessment included MADRS total score and CGI-BP-S total score, the secondary efficacy assessment included the response and the remission rates and the safety and tolerability were also evaluated applying the Simpson-Angus Scale. RESULTS: The meta-analysis compromised 7 studies. Efficacy analysis suggested that lurasidone was more effective than placebo: MADRS total score (MD:-4.31, 95%CI: (-6.93,-1.7), P = 0.001) and the CGI-BP-S total score (MD:-0.37, 95%CI: (-0.59,-0.15), P = 0.0008) were obtained for both lurasidone-treated and placebo groups. Response rates (RR: 1.73, 95%CI: (1.46, 2.05), P < 0.00001) and Remission rates (RR: 1.57, 95%CI: (1.38, 1.79), P < 0.00001). The safety analysis between lurasidone and placebo showed no difference: at least one event (RR: 1.12, 95% CI :(1.00, 1.26), p = 0.05 and the influence on glucose (MD: 0.35, 95% CI :(-1.09, 1.79), p = 0.63. LIMITATION: The present conclusion is limited by the limited included studies. The different dose of lurasidone should be considered in the future. CONCLUSION: Compared with placebo, adjunctive lurasidone significantly improved depressive symptoms and is very well tolerated with minimal side effects on the endocrine and cardiovascular systems in clinical patients with bipolar I depression. Key words: Bipolar I depression; Lurasidone; Meta-analysis; Remission rates; Adverse effect.

Elevated plasma D-dimer levels are associated with short-term poor outcome in patients with acute ischemic stroke: a prospective, observational study.

BACKGROUND: Elevated levels of plasma D-dimer increase the risk of ischemic stroke, stroke severity, and the progression of stroke status, but the association between plasma D-dimer level and functional outcome is unclear. The aim of this study is to investigate whether plasma D-dimer level is a determinant of short-term poor functional outcome in patients with acute ischemic stroke (AIS). METHODS: This prospective study included 877 Chinese patients with AIS admitted to Renmin Hospital of Wuhan University within 72 h of symptom onset. Patients were categorized by plasma D-dimer level: Quartile 1(≤0.24 mg/L), Quartile 2 (0.25-0.56 mg/L), Quartile 3 (0.57-1.78 mg/L), and Quartile 4 (> 1.78 mg/L). The medical record of each patient was reviewed, and demographic, clinical, laboratory and neuroimaging information was abstracted. Functional outcome at 90 days was assessed with the modified Rankin Scale. RESULTS: Poor outcome was present in 302 (34.4%) of the 877 patients that were included in the study (mean age, 64 years; male, 68.5%). After adjustment for potential confounding variables, higher plasma D-dimer level on admission was associated with poor outcome (adjusted odds ratio 2.257, 95% confidence interval 1.349-3.777 for Q4:Q1; P trend = 0.004). According to receiver operating characteristic (ROC) analysis, the best discriminating factor for poor outcome was a plasma D-dimer level ≥ 0.315 mg/L (area under the ROC curve 0.657; sensitivity 83.8%; specificity 41.4%). CONCLUSION: Elevated plasma D-dimer levels on admission are significantly associated with poor outcome after admission for AIS, suggesting the potential role of plasma D-dimer level as a predictive marker for short-term poor outcome in patients with AIS.

Psychological factors influencing choice of prenatal diagnosis in Chinese multiparous women with advanced maternal age.

OBJECTIVES: To investigate the psychological predictors in Chinese multiparous pregnant women of advanced maternal age (AMA) for choosing aneuploidy screening or diagnostic testing. METHODS: A total of 84 pregnant women of AMA were consecutively enrolled from Renming Hospital, Wuhan University. All participants completed three questionnaires: Zung Self-Rating Anxiety Scale (SAS), Zung Self-Rating Depression Scale (SDS), and Pregnancy Stress Rating Scale (PSRS). Demographic information and the choice of noninvasive prenatal testing (NIPT) versus invasive prenatal diagnosis (PND) were also collected. RESULTS: Thirty-seven chose to have invasive PND, and 47 chose NIPT. Choosing invasive PND, as opposed to NIPT, was associated with lower educational background (χ2 = -2.269, p = .023), higher SAS scores (47.62 ± 7.96 versus 44.21 ± 6.10, p = .029), and higher SDS scores (50.41 ± 9.80 versus 45.96 ± 11.05, p = .058). Logistic regression analysis further showed that the decisive predictors for invasive PND are SAS (OR =1.106, p = .008) scores, scores of factor 3 in PSRS and the stress from changes of shape and motility (OR =0.471, p = .038). Subgroup analysis showed that women with previous negative pregnancy experience had higher scores in factor 2-stress (guarantee of maternal-fetal safety: 1.96 ± 0.63 versus 2.49 ± 0.65, p = .004) and total PSRS scores (1.60 ± 0.4 versus 1.83 ± 0.31, p = .044) than those without. Additionally, unemployment post pregnancy was associated with marginally significant higher PSRS scores (p = .083). CONCLUSIONS: The decision for invasive PND might be swayed by anxiety and attenuated by pregnancy stress originating from worry about changes in fetal shape and motility (measured by SAS and factor 3 score of PSRS, respectively).

Selection and measurement of control antidepressants in clinical tests for Chinese: A systematic review.

OBJECTIVE: The study aims to help domestic application units and research institutions improve their research quality of antidepressant clinical tests by studying and analyzing the current status and problems in selecting control drugs during domestic antidepressant clinical tests and illustrating some key problems that should be noted when selecting the control drug in such researches. METHODS: Considering the current domestic and overseas status of control drug selection in antidepressant clinical tests, various considerations, and misunderstandings on control drug selection in domestic antidepressant clinical tests were clarified and described, and possible factors that may influence the absolute effect of antidepressants were analyzed. Furthermore, problems that should be noted in selecting control drugs for the antidepressant clinical test, especially the placebo control, were stated. RESULTS: During the antidepressant clinical research, selecting placebo controls conform to moral philosophy and safety requirements. To verify the absolute effect of a test drug, a placebo control should be set or 3-arm tests should be conducted as far as possible. Possible factors that may affect the absolute effect of the test drug, including illness severity of the subject at baseline and research scale, should be given consideration. CONCLUSIONS: Application units and research institutions should consider the selection of subjects, control the failure rate, strengthen safety risks, and control and intensify quality control to further improve the overall quality and research level of domestic antidepressant clinical tests.

Adjunctive antidepressant use in schizophrenia in China: A national survey (2002-2012).

OBJECTIVE: This study examined the pattern of adjunctive antidepressant use in schizophrenia patients and its demographic and clinical correlates in a nationwide survey in China. METHODS: Fourteen thousand and thirteen patients in 45 Chinese psychiatric hospitals or centers were interviewed (4,486 in 2002, 5,288 in 2006, and 4,239 in 2012). Patients' sociodemographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. Chi-square test, independent-samples t test, Mann-Whitney U test, and multiple logistic regression analysis were used in data analyses. RESULTS: Antidepressant use was found in 5.2% of the study population with 4.6% in 2002, 4.3% in 2006, and 6.9% in 2012, respectively. A significant increase in use from 2006 to 2012 was found (p < .001). Multiple logistic regression analyses in the whole population revealed that patients receiving adjunctive antidepressants were more likely to be outpatients in tertiary referral centers (level-III hospitals) and who had an earlier age of onset, less severe global illness, but more depressive symptoms. They were less likely to receive first-generation antipsychotics but more likely to receive benzodiazepines (R2  = 0.255, p < .001). CONCLUSIONS: Despite an increasing trend, the frequency of antidepressant use in schizophrenia in China was considerably lower than in Western countries. The benefits and risks associated with concomitant use of antidepressants in schizophrenia need to be studied further.

Electroconvulsive Therapy in Schizophrenia in China: A National Survey.

OBJECTIVE: Little is known about electroconvulsive therapy (ECT) use in the treatment of schizophrenia in China. This study examined the frequency of ECT use, its trend between 2006 and 2012, and its independent demographic and clinical correlates in a nationwide survey in China. METHODS: A total of 5162 inpatients in 45 Chinese psychiatric hospitals/centers were interviewed (2696 in 2006 and 2466 in 2012). Patients' sociodemographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. RESULTS: Electroconvulsive therapy was used in 6.1% of the whole sample; 4.7% in 2006 and 7.7% in 2012 (P < 0.001) with wide interprovince variations. Multiple logistic regression analyses of the whole sample revealed that patients receiving ECT were more likely to be women, receive second-generation antipsychotics, treated in tertiary referral centers (level III hospitals), had a shorter illness duration, and more positive and depressive symptoms (R = 0.181; P < 0.001). CONCLUSIONS: Electroconvulsive therapy for schizophrenia has increased between 2006 and 2012 in China. Its percentage was higher than the figures reported in most other countries. Reasons for the substantial variations in the frequency of ECT across different provinces in China require further investigations.

Abnormal Degree Centrality of Bilateral Putamen and Left Superior Frontal Gyrus in Schizophrenia with Auditory Hallucinations: A Resting-state Functional Magnetic Resonance Imaging Study.

BACKGROUND: Dysconnectivity hypothesis of schizophrenia has been increasingly emphasized. Recent researches showed that this dysconnectivity might be related to occurrence of auditory hallucination (AH). However, there is still no consistent conclusion. This study aimed to explore intrinsic dysconnectivity pattern of whole-brain functional networks at voxel level in schizophrenic with AH. METHODS: Auditory hallucinated patients group (n = 42 APG), no hallucinated patients group (n = 42 NPG) and normal controls (n = 84 NCs) were analyzed by resting-state functional magnetic resonance imaging. The functional connectivity metrics index (degree centrality [DC]) across the entire brain networks was calculated and evaluated among three groups. RESULTS: DC decreased in the bilateral putamen and increased in the left superior frontal gyrus in all the patients. However, in APG, the changes of DC were more obvious compared with NPG. Symptomology scores were negatively correlated with the DC of bilateral putamen in all patients. AH score of APG positively correlated with the DC in left superior frontal gyrus but negatively correlated with the DC in bilateral putamen. CONCLUSION: Our findings corroborated that schizophrenia was characterized by functional dysconnectivity, and the abnormal DC in bilateral putamen and left superior frontal gyrus might be crucial in the occurrence of AH.

Clozapine in schizophrenia and its association with treatment satisfaction and quality of life: Findings of the three national surveys on use of psychotropic medications in China (2002-2012).

OBJECTIVE: We examined the time trends and correlates of clozapine use in schizophrenia patients in China. METHOD: A total of 14,013 patients with schizophrenia treated in 45 psychiatric hospitals/centers nationwide were interviewed in 2002, 2006 and 2012. Patients' socio-demographic and clinical characteristics including psychopathology, medication side effects, satisfaction with treatment and quality of life (QOL) were recorded in a standardized fashion. RESULTS: Clozapine was used in 32.9% of the whole sample; with corresponding figures of 39.7%, 32.5% and 26.4% in 2002, 2006 and 2012 (p<0.001). Families of clozapine users had lower satisfaction with treatment than those of the non-clozapine group, without significant differences with respect to patients' treatment satisfaction and mental or physical QOL. In multiple logistic regression analyses, compared to the non-clozapine group, patients on clozapine had an earlier age of onset, longer illness duration, more global illness severity and drug-induced central nervous system, gastrointestinal and other side effects, lower antipsychotic doses, less delusions and hallucinations, more negative symptoms, were more likely male, inpatients, to have a family history of psychiatric disorders, receive treatments in regional centers and receive antipsychotic polypharmacy, but less likely to have health insurance and receive first-generation antipsychotics and benzodiazepines (R(2)=0.498, p<0.001). CONCLUSIONS: Clozapine was used in one-third of schizophrenia patients in China, with decreasing frequency since 2002. Patients prescribed clozapine had multiple markers of greater global illness severity/chronicity and decreased satisfaction with treatment by the families, but similar QOL and less delusions and hallucinations than patients not prescribed clozapine.

Antipsychotic Medications in Major Depression and the Association with Treatment Satisfaction and Quality of Life: Findings of Three National Surveys on Use of Psychotropics in China Between 2002 and 2012.

BACKGROUND: Optimizing treatment outcomes for depression requires understanding of how evidence-based treatments are utilized in clinical practice. Antipsychotic medications concurrent with antidepressant treatment are frequently used in major depression, but few studies have investigated trends and patterns of their use over time. This study aimed to examine the prescription patterns of antipsychotic medications for major depression in China from 2002 to 2012 and their association with treatment satisfaction and quality of life (QOL). METHODS: A total of 3655 subjects with major depression treated in 45 Chinese psychiatric hospitals/centers nationwide were interviewed between 2002 and 2012. Patients' socio-demographic and clinical characteristics including psychopathology, medication side effects, satisfaction with treatment and QOL were recorded using a standardized protocol and data collection. RESULTS: The frequency of antipsychotic use was 24.9% in the whole sample; the corresponding figures were 17.1%, 20.3%, and 32.8% in 2002, 2006, and 2012, respectively (χ2 = 90.3, df = 2, P < 0.001). Multiple logistic regression analyses revealed that patients on concurrent antipsychotics had significantly more delusions or hallucinations, longer illness duration, greater side effects, and more likely to be treated as inpatients and in major hospitals (i.e., Level-III hospital). Antipsychotic use was associated with lower treatment satisfaction while there was no significant difference with respect to physical and mental QOL between the antipsychotic and nonantipsychotic groups. CONCLUSIONS: Concurrent antipsychotic use was found in about one in four treated depressed patients in China, which has increased over a 10-year period. Considering the association of drug-induced side effects and the lack of patients' and relatives' satisfaction with antipsychotic treatment, further examination of the rationale and appropriateness of the use of antipsychotics in depression is needed.

WSKY, a traditional Chinese decoction, rescues cognitive impairment associated with NMDA receptor antagonism by enhancing BDNF/ERK/CREB signaling.

Warm­supplementing kidney yang (WSKY) is an herbal prescription that has been used in Traditional Chinese Medicine for the treatment of psychiatric conditions. A previous study by our group found that WSKY significantly improved cognitive function of schizophrenia patients. In the present study, the effects of WSKY on cognitive function and their underlying mechanisms were investigated. WSKY was administered to an MK­801­induced rat model of chronic schizophrenia for 14 days. Memory performance was assessed using the Morris water maze (MWM) test. The expression of brain­derived neurotrophic factor (BDNF), activation of cAMP response element binding protein (pCREB/CREB) and activation of extracellular signal­regulated kinase (pERK/ERK) in the hippocampus was detected using western blot analysis. In the acquisition phase of the MWM test, the escape latency was significantly increased in the MK­801­treated group compared with the normal control group (P<0.01). Treatment with WSKY for 14 days at doses of 100 or 250 mg/kg rescued this cognitive impairment (P<0.05). In the probe test, 250 mg/kg WSKY treatment increased the time spent in the target quadrant (P<0.05) and number of platform crossings (P<0.01). Western blot analysis demonstrated that the levels of BDNF expression in the hippocampus of rats without behavioral tests were elevated following 14 days of WSKY treatment, and the effect of WSKY treatment on hippocampal BDNF expression was presented in an inverted U­shaped dose­response pattern. The pERK1/2 in the hippocampus was significantly enhanced following 100 mg/kg (P<0.01) and 250 mg/kg (P<0.01) WSKY treatment, while only 250 mg/kg WSKY increased the phosphorylation of CREB (P<0.01). The results of the present study indicated that WSKY enhances cognitive performance via the upregulation of BDNF/ERK/CREB signaling, and that WSKY has potential therapeutic implications for cognitive impairment of schizophrenia.

Antipsychotic polypharmacy in schizophrenia patients in China and its association with treatment satisfaction and quality of life: findings of the third national survey on use of psychotropic medications in China.

OBJECTIVE: This study examined the use, demographic and clinical correlates of antipsychotic polypharmacy (APP) and its associations with treatment satisfaction and quality of life (QOL) in schizophrenia patients in China. METHOD: A total of 4239 patients in 45 nationwide Chinese psychiatric hospitals/centers were interviewed in 2012 in the third cross-sectional study, with the first two having been conducted in 2002 and 2006. Patients' socio-demographic and clinical characteristics, including psychopathology, side effects, satisfaction with treatment and QOL, were recorded using a standardized protocol and data collection procedure. RESULTS: The proportion of APP prescriptions in 2012 was 34.2%, which was significantly higher than the frequency of APP in 2002 (26.1%) and 2006 (26.4%) (p<0.001). Of patients on APP, 91.1% received two antipsychotics, 8.6% received three and 0.3% received four or more antipsychotics. Multiple logistic regression analyses revealed that compared to those on antipsychotic monotherapy, patients on APP and their families had lower satisfaction with treatment, had higher QOL in the mental domain, younger age of onset, more side effects, higher doses of antipsychotics and were more likely to receive first-generation antipsychotics and less likely to receive benzodiazepines (total R (2)=0.31, p<0.001). CONCLUSIONS: APP was found in about one in three schizophrenia patients. The prevalence of APP seems to have been increasing since 2002. Considering the increased frequency of drug-induced side effects and the patients' and their relatives' dissatisfaction with antipsychotic treatment, further examination of the rationale and appropriateness of APP and its alternatives is warranted.