Methods for online calibration of Q-matrix and item parameters for polytomous responses in cognitive diagnostic computerized adaptive testing.

The ability to rapidly provide examinees with detailed and effective diagnostic information is a critical topic in psychology. Knowing what diagnostic criteria the examinees have met enables the practitioner to seek the solution to help them in a timely manner, and this can be achieved by cognitive diagnostic computerized adaptive testing (CD-CAT). However, the pervasive challenge of replenishing items in the CD-CAT item bank limits its practical application. Online calibration is a means to address item replenishment, but in CD-CAT, most existing online calibration methods that jointly calibrate the Q-matrix and item parameters of the new items are developed only for dichotomous responses and are time-consuming. Notably, previous studies pay no attention to polytomously scored items that are frequently observed in testing, even though they can offer additional evidence for the examinees' diagnosis. To fill this gap, we propose a SCAD-based method (SCAD-EM) to calibrate the Q-matrix and item parameters of the new items with polytomous response data in order to promote the application of CD-CAT in practice. The performance of the SCAD-EM was investigated in two comprehensive simulation studies and compared against the revised single-item estimation method (SIE-BIC). Results indicated that the SCAD-EM produces a higher calibration accuracy for the category-level Q-matrix and is computationally more efficient across all conditions, but it produces a lower calibration accuracy for the item-level Q-matrix. An empirical study further demonstrated the utility of the SCAD-EM and the SIE-BIC methods in calibrating new items with a real dataset. The advantages of the proposed method, its limitations, and possible future research directions are offered at the end.

Clinicodemographic correlates of psychotic features in bipolar disorder - a multicenter study in China.

BACKGROUND: Psychotic symptoms are prevalent in patients with bipolar disorder (BD). However, nearly all previous studies on differences in sociodemographic and clinical factors between patients with (BD P +) and without (BD P-) psychotic symptoms were conducted in Western populations, and limited information is known in China. METHOD: A total of 555 patients with BD from seven centers across China were recruited. A standardized procedure was used to collect patients' sociodemographic and clinical characteristics. The patients were divided into BD P + or BD P- groups based on the presence of lifetime psychotic symptoms. Mann-Whitney U test or chi-square test was used to analyze differences in sociodemographic and clinical factors between patients with BD P + and BD P-. Multiple logistic regression analysis was conducted to explore factors that were independently correlated with psychotic symptoms in BD. All the above analyses were re-conducted after the patients were divided into BD I and BD II group according to their types of diagnosis. RESULTS: A total of 35 patients refused to participate, and the remaining 520 patients were included in the analyses. Compared with patients with BD P-, those with BD P + were more likely to be diagnosed with BD I and mania/hypomania/mixed polarity in the first mood episode. Moreover, they were more likely to be misdiagnosed as schizophrenia than major depressive disorder, were hospitalized more often, used antidepressants less frequently, and used more antipsychotics and mood stabilizers. Multivariate analyses revealed that diagnosis of BD I, more frequent misdiagnosis as schizophrenia and other mental disorders, less frequent misdiagnosis as major depressive disorder, more frequent lifetime suicidal behavior, more frequent hospitalizations, less frequent use of antidepressants, more frequent use of antipsychotics and mood stabilizers were independently correlated with psychotic symptoms in BD. After dividing the patients into BD I and BD II groups, we observed notable differences in sociodemographic and clinical factors, as well as clinicodemographic correlates of psychotic features between the two groups. CONCLUSIONS: Differences in clinical factors between patients with BD P + and BD P- showed cross-cultural consistency, but results on the clinicodemographic correlates of psychotic features were not. Notable differences between patients with BD I and BD II were found. Future work exploring the psychotic features of BD needs to take types of diagnosis and cultural differences into consideration. TRIAL REGISTRATION: This study was first registered on the website of the ClinicalTrials.gov ( https://clinicaltrials.gov/ ) on 18/01/2013. Its registration number is NCT01770704.

Application of case-based learning in psychology teaching: a meta-analysis.

BACKGROUND: Case-based learning (CBL) has been found to be effective for many subjects, but there is currently a lack of evidence regarding its utility in psychology education. The present study investigated whether CBL pedagogy can improve students' academic performance in psychology courses compared to the traditional teaching methods. METHODS: A systematic review and meta-analysis were conducted to investigate the effectiveness of CBL in psychology teaching. Databases including PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), the VIP database, and Wanfang data were searched to find eligible randomized controlled trials. Pooled effect estimates were calculated using Hedges' g under the random effects model, and a subgroup analysis was carried to investigate the heterogeneity among studies. RESULTS: Fifteen studies with 2172 participants, 1086 in the CBL group and 1086 in the traditional lecture-based teaching group, were included in the meta-analysis. Students in the CBL group scored significantly higher on exams than those in the lecture-based group [Hedges' g = 0.68, 95%CI (0.49, 0.88), p < 0.00]. Relatively high heterogeneity was noted among the included studies. Publication bias was examined by the funnel plot and Egger's test, but did not significantly influence the stability of the results. A subsequent evaluation using the trim-and-fill method confirmed that no single study was skewing the overall results. A qualitative review of the included studies suggested that most students in the CBL group were satisfied with the CBL teaching mode. CONCLUSIONS: This meta-analysis indicated that the CBL pedagogy could be effective in psychology education, and might help increase students' academic scores, while encouraging a more engaging and cooperative learning environment. At present, the application of CBL in psychology education is in its initial stage. Problems related to the curriculum itself, research methodology, and challenges faced by both teachers and learners have confined its practice. Fully tapping into the strengths of CBL in psychology teaching will require additional work and advancing research.

Efficacy, Safety, and Tolerability of Ansofaxine (LY03005) Extended-Release Tablet for Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled, Dose-Finding, Phase 2 Clinical Trial.

BACKGROUND: Ansofaxine (LY03005) extended-release tablet is a potential triple reuptake inhibitor of serotonin, norepinephrine, and dopamine. This study assessed the efficacy, safety, and appropriate dosage of ansofaxine for the treatment of major depressive disorder (MDD). METHODS: A multicenter, randomized, double-blind, placebo-controlled, dose-finding, Phase 2 clinical trial was conducted in China. Eligible patients with MDD (18-65 years) were randomly assigned to receive fixed-dose ansofaxine extended-release tablets (40, 80, 120, or 160 mg/d) or placebo for 6 weeks. The primary outcome measure was a change in the total score on the 17-item Hamilton Depression Rating Scale from baseline to week 6. RESULTS: A total of 260 patients were recruited from October 2015 to September 2017, and 255 patients received the study drug as follows: 40 mg (n = 52), 80 mg (n = 52), 120 mg (n = 51), and 160 mg (n = 51) ansofaxine and placebo (n = 49). Significant differences were found in mean changes in 17-item Hamilton Depression Rating Scale total scores at week 6 in the 4 ansofaxine groups vs placebo (-12.46; χ2 = -9.71, P = .0447). All doses of ansofaxine were generally well-tolerated. Treatment-related adverse events occurred in 141 patients (303 cases), yielding incidence rates of 51.92%, 65.38%, 56.86%, and 62.75% in the 40-, 80-, 120-, and 160-mg ansofaxine groups and 38.78% in the placebo group. CONCLUSION: Active doses (40, 80, 120, and 160 mg/d) of ansofaxine in a controlled setting were safe, tolerated, and effective in improving depression symptoms in MDD patients.

Alterations in Plasma Lipidomic Profiles in Adult Patients with Schizophrenia and Major Depressive Disorder.

Background and Objectives: Lipidomics is a pivotal tool for investigating the pathogenesis of mental disorders. However, studies qualitatively and quantitatively analyzing peripheral lipids in adult patients with schizophrenia (SCZ) and major depressive disorder (MDD) are limited. Moreover, there are no studies comparing the lipid profiles in these patient populations. Materials and Method: Lipidomic data for plasma samples from sex- and age-matched patients with SCZ or MDD and healthy controls (HC) were obtained and analyzed by liquid chromatography-mass spectrometry (LC-MS). Results: We observed changes in lipid composition in patients with MDD and SCZ, with more significant alterations in those with SCZ. In addition, a potential diagnostic panel comprising 103 lipid species and another diagnostic panel comprising 111 lipid species could distinguish SCZ from HC (AUC = 0.953) or SCZ from MDD (AUC = 0.920) were identified, respectively. Conclusions: This study provides an increased understanding of dysfunctional lipid composition in the plasma of adult patients with SCZ or MDD, which may lay the foundation for identifying novel clinical diagnostic methods for these disorders.

Prescription practices in the treatment of agitation in newly hospitalized Chinese schizophrenia patients: data from a non-interventional naturalistic study.

BACKGROUND: Data on the pharmacological management of acute agitation in schizophrenia are scarce. The aim of this study is to investigate the prescription practices in the treatment of agitation in Chinese patients with schizophrenia. METHODS: We conducted a large, multicenter, observational study in 14 psychiatry hospitals in China. Newly hospitalized schizophrenia patients with the PANSS-EC total score ≥ 14 and a value ≥4 on at least one of its five items were included in the study. Their drug treatments of the first 2 weeks in hospital were recorded by the researchers. RESULTS: Eight hundred and 53 patients enrolled in and 847 (99.30%) completed the study. All participants were prescribed antipsychotics, 40 (4.72%) were prescribed benzodiazepine in conjunction with antipsychotics and 81 were treated with modified electric convulsive therapy (MECT). Four hundred and 12 (48.64%) patients were prescribed only one antipsychotic, in the order of olanzapine (120 patients, 29.13%), followed by risperidone (101 patients, 24.51%) and clozapine (41 patients, 9.95%). About 435 (51.36%) participants received antipsychotic polypharmacy, mostly haloperidol + risperidone (23.45%), haloperidol+ olanzapine (17.01%), olanzapine+ ziprasidone (5.30%), haloperidol + clozapine (4.37%) and haloperidol + quetiapine (3.90%). Binary logistic regression analysis suggests that a high BARS score (OR 2.091, 95%CI 1.140-3.124), severe agitation (OR 1.846, 95%CL 1.266-2.693), unemployment or retirement (OR 1.614, 95%CL 1.189-2.190) and aggressiveness on baseline (OR 1.469, 95%CL 1.032-2.091) were related to an increased antipsychotic polypharmacy odds. Male sex (OR 0.592, 95%CL 0.436-0.803) and schizophrenia in older persons (age ≥ 55 years, OR 0.466, 95%CL 0.240-0.902) were less likely to be associated with antipsychotic polypharmacy. CONCLUSION: The present study demonstrates that monotherapy and polypharmacy display equally common patterns of antipsychotic usage in managing agitation associated with schizophrenia in China. The extent and behavioral activities of agitation and several other factors were associated with polypharmacy.

Transcutaneous electrical acupoint stimulation for post-traumatic stress disorder: Assessor-blinded, randomized controlled study.

AIM: Transcutaneous electrical acupoint stimulation (TEAS) has the potential to alleviate post-traumatic stress disorder (PTSD). The purpose of this study was to determine whether adding TEAS to sertraline or cognitive behavioral therapy (CBT) could improve the anti-PTSD efficacy. METHODS: In this randomized controlled trial, 240 PTSD patients (60 in each group) were assigned to receive simulated TEAS combined with sertraline (group A) or with CBT (group B), active TEAS combined with CBT (group C), or active TEAS combined with CBT plus sertraline (group D) for 12 weeks. The outcomes were measured using the Clinician-Administered PTSD Scale, PTSD Check List-Civilian Version, and 17-item Hamilton Rating Scale for Depression. RESULTS: While PTSD symptoms reduced over time in all patients, groups C and D had markedly greater improvement in both PTSD and depressive measures than groups A and B in all post-baseline measurement points, with moderate to very large effect sizes of 0.484-2.244. Groups C and D also had a significantly higher rate than groups A and B on clinical response (85.0% and 95.0% vs 63.3% and 60.0%, P < 0.001) and on remission (15.0% and 25.0% vs 3.3% and 1.7%, P < 0.001). The incidence of adverse events was similar between groups A and D and between groups B and C. CONCLUSIONS: Additional TEAS augments the anti-PTSD and antidepressant efficacy of antidepressants or CBT, without increasing the incidence of adverse effects. TEAS could serve as an effective intervention for PTSD and comorbid depression. This trial was registered with www.chictr.org (no.: ChiCTR1800017255).

Repetitive transcranial magnetic stimulation inhibits Sirt1/MAO-A signaling in the prefrontal cortex in a rat model of depression and cortex-derived astrocytes.

Repetitive transcranial magnetic stimulation (rTMS) is a useful monotherapy for depression or adjunctive therapy for resistant depression. However, the anti-depressive effects of different parameters and the underlying mechanisms remain unclear. Here, we aimed to assess the effect of rTMS with different parameters (1/5/10 Hz, 0.84/1.26 T) on the depressive-like behaviors, 5-hydroxytryptamine (5-HT), 5-HIAA (5-hydroxyindoleacetic acid) and DA and NE levels, and monoamine oxidase A (MAO-A) activity in chronic unpredictable stress-treated rats, along with the expression of sirtuin 1 (Sirt1) and MAO-A in the prefrontal cortex (PFC) and cortex-derived astrocytes from new-born rats. Moreover, the depressive-like behaviors were monitored following the transcranial injection of the Sirt1 inhibitor EX527 (1 mM) daily for 1 week. We found that rTMS treatment (5/10 Hz, 0.84/1.26 T) ameliorated depressive-like behaviors, increased 5-HT, DA and NE levels, decreased the 5-HIAA level and Sirt1 and MAO-A expression, and reduced MAO-A activity in the PFC. The depressive-like behaviors were also ameliorated after the transcranial injection of EX527. Importantly, rTMS (5/10 Hz, 0.84/1.26 T) inhibited Sirt1 and MAO-A expressions in astrocytes and Sirt1 knockdown with short hairpin RNA decreased MAO-A expression in astrocytes. These results suggest that the inhibition of Sirt1/MAO-A expression in astrocytes in the PFC may contribute to the different anti-depressive effects of rTMS with different parameters, and may also provide a novel insight into the mechanisms underlying major depressive disorder.

A Case of Fronto-Temporal Dementia (FTD) Masquerading as Mood Disorder.

A 56-year old Chinese female was referred to an academic medical center with atypical, treatment-resistant depression that continued for approximately 3 years after her sister's death. Comprehensive evaluation including neurocognitive testing, EEG, spinal tap, HIV testing and brain MRI revealed behavioral variant of fronto-temporal dementia (bvFTD) with significant frontal and temporal lobe atrophy.This patient's unusual clinical presentation emphasizes the overlap between depression and bvFTD, and underlines the importance of prompt, accurate diagnosis to minimize often-ineffective pharmacological interventions and caregiver burnout.

Peony-Glycyrrhiza Decoction for Antipsychotic-Related Hyperprolactinemia in Women With Schizophrenia: A Randomized Controlled Trial.

OBJECTIVES: An herbal preparation called peony-glycyrrhiza decoction (PGD) may have the potential in reducing antipsychotic-related hyperprolactinemia (hyperPRL). This double-blind, randomized placebo-controlled study aimed to reevaluate the efficacy of PGD against antipsychotic-related hyperPRL. METHODS: Ninety-nine schizophrenic women who were under antipsychotic therapy and had symptomatic hyperPRL were randomly assigned to additional treatment with placebo (n = 50) or PGD (n = 49, 45 g/d) for 16 weeks. The severity of hyperPRL, psychosis, and abnormal involuntary movements was assessed at baseline and weeks 8 and 16 using standard instruments including the Prolactin Related Adverse Event Questionnaire. Blood levels of prolactin (PRL) and related pituitary and sex hormones were measured at the same time points. RESULTS: Peony-glycyrrhiza decoction treatment produced a significantly greater reduction of the Prolactin Related Adverse Event Questionnaire score at weeks 8 and 16 and a greater improvement on abnormal involuntary movements at end point compared with placebo, without altering the severity of psychosis. The group treated with PGD showed significantly higher proportion of having overall improvement on hyperPRL symptoms (χ = 4.010, P = 0.045) and menstrual resumption (χ = 4.549, P = 0.033) at week 8 than placebo. Serum PRL levels were similar in the 2 groups. CONCLUSIONS: Peony-glycyrrhiza decoction is effective in reducing antipsychotic-related hyperPRL and abnormal involuntary movement symptoms, but no reduction in blood PRL concentrations was observed. The underlying mechanisms of PGD's effects need further investigation (trial registration of NCT01852331 at www.clinicaltrials.gov).

Peony-Glycyrrhiza Decoction, an Herbal Preparation, Inhibits Clozapine Metabolism via Cytochrome P450s, but Not Flavin-Containing Monooxygenase in In Vitro Models.

Our previous studies have shown the therapeutic efficacy and underlying mechanisms of Peony-Glycyrrhiza Decoction (PGD), an herbal preparation, in treating antipsychotic-induced hyperprolactinemia in cultured cells, animal models, and human subjects. In the present study, we further evaluated pharmacokinetic interactions of PGD with clozapine (CLZ) in human liver microsomes (HLM), recombinantly expressed cytochrome P450s (P450s), and flavin-containing monooxygenases (FMOs). CLZ metabolites, N-demethyl-clozapine and clozapine-N-oxide, were measured. PGD, individual peony and glycyrrhiza preparations, and the two individual preparations in combination reduced production of CLZ metabolites to different extents in HLM. While the known bioactive constituents of PGD play a relatively minor role in the kinetic effects of PGD on P450 activity, PGD as a whole had a weak-to-moderate inhibitory potency toward P450s, in particular CYP1A2 and CYP3A4. FMOs are less actively involved in mediating CLZ metabolism and the PGD inhibition of CLZ. These results suggest that PGD has the capacity to suppress CLZ metabolism in the human liver microsomal system. This suppression is principally associated with the inhibition of related P450 activity but not FMOs. The present study provides in vitro evidence of herb-antipsychotic interactions.

Quetiapine Ameliorates Schizophrenia-Like Behaviors and Protects Myelin Integrity in Cuprizone Intoxicated Mice: The Involvement of Notch Signaling Pathway.

BACKGROUND: White matter disturbances and myelin impairment are key features of schizophrenia. The antipsychotic drug quetiapine can promote the maturation of oligodendrocytes, but the molecular mechanisms remain largely unknown. METHODS: The schizophrenia-like behaviors, degrees of demyelination, and levels of Notch signaling molecules in forebrains of adult male C57BL/6 mice were examined after fed with cuprizone (0.2% wt/wt) in the presence or absence of 10mg/kg/d quetiapine for 6 weeks. These parameters were also observed after the transcranial injection of Notch signaling inhibitor MW167 (1mM) daily during the last week of the treatment period. RESULTS: Quetiapine ameliorated the schizophrenia-like behaviors and decreased expression of myelin basic protein and inhibition of Notch signaling molecules, such as Notch1, Hes1, and Hes5, in the forebrain that induced by cuprizone. These beneficial effects of quetiapine were abolished by MW167. CONCLUSIONS: The antipsychotic and myelin protective effects of quetiapine are mediated by Notch signaling in a mouse model of cuprizone-induced demyelination associated with schizophrenia-like behaviors. The Notch pathway might therefore be a novel target for the development of antipsychotic drugs.

Gastrodin alleviates cerebral ischemic damage in mice by improving anti-oxidant and anti-inflammation activities and inhibiting apoptosis pathway.

Gastrodin (GAS), an active constituent of the Chinese herbal medicine Tianma, has anti-oxidant and anti-inflammation activities but its protective effect to the prevention of neurotoxicity induced by ischemic stroke is unclear. In the present study, middle cerebral artery occlusion (MCAO) was used to establish a mice ischemic stroke model. Infarct volume ratio and neurobehavioral score were evaluated, Nissl staining was performed and the expression of cleaved Caspase 3, Bax and B cell lymphoma 2 (Bcl-2) were assessed at 24 h or 7 days after reperfusion. In addition, the total superoxide dismutase (SOD) activity and malondialdehyde (MDA) content, as well as the expression of Nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), SOD1, phospho-Akt and total Akt and TNF-α and IL-1ß in the ischemic hemispheres were also observed at 6 h after reperfusion to assess oxidative stress and inflammatory changes after GAS treatment. It was found that GAS, especially at high dose (100 mg/kg) reduced tested neuronal injury and neurobehavioral deficient in MCAO mice. Enhanced expression of cleaved Caspase 3 and Bax and decreased expression of Bcl-2 by MCAO were also reversed by GAS. Moreover, GAS treatment decreased the MDA content and the expression of TNF-α and IL-1ß, and increased amount of SOD activity and the expression of HO-1 and SOD1 in GAS-treated ischemic brain. Furthermore, GAS significantly increased Akt phosphorylation and Nrf2 expression. These results support the neuroprotective effects of GAS, and the activation of Akt/Nrf2 pathway may play a critical role in the pharmacological action of GAS.

Gastrodin ameliorates depressive-like behaviors and up-regulates the expression of BDNF in the hippocampus and hippocampal-derived astrocyte of rats.

Gastrodin (GAS), a main constituent of a Chinese herbal medicine Tian ma, has been shown to be effective in treating various mood disorders. The purpose of the present study was to assess the effects of GAS on alleviating depressive-like behaviors in a rat model of chronic unpredictable stress (CUS) and regulating the expression of BDNF in the hippocampus and hippocampal-derived astrocyte from Sprague-Dawley (SD) rats. Following CUS, rats were intraperitoneally administered gastrodin (50, 100, or 200 mg/kg daily) or vehicle for 2 weeks. Rats were then experienced sucrose preference test and forced swim test. The expressions of GFAP and BDNF in the hippocampus were evaluated. In addition, hippocampal astrocytes were isolated from neonatal SD rats and exposed to different concentrations of GAS (sham, 5, 10, 20, 50 and 100 µg/mL) for 48 and 72 h before the cell viability and the levels of pERK1/2 and BDNF were analyzed. Furthermore, the cell viability was also tested after exposure to serum-free condition that contain different concentrations of GAS for 48 and 72 h. GAS administration (100 and 200 mg/kg daily) reversed depressive-like behaviors in rats exposed to CUS paradigm and restored the expression of GFAP and BDNF in the hippocampus. Moreover, in vitro experiments revealed that GAS did not increase the cell viability of astrocytes but protected it from 72 h's serum-free damage at the dosage 20 µg/mL. Increased levels of ERK1/2 phosphorylation and BDNF protein were also observed after GAS (20 µg/mL) treatment for 72 h. These results indicate that gastrodin possesses antidepressant effect. The changes of the astrocyte activation and the level of BDNF may play a critical role in the pharmacological action of GAS.

Efficacy and safety of prolonged-release trazodone in major depressive disorder: a multicenter, randomized, double-blind, flexible-dose trial.

OBJECTIVE: To investigate the efficacy, safety, and clinical benefit of prolonged-release trazodone (Trittico) in the treatment of major depressive disorder (MDD). METHODS: In this study, 363 Chinese patients with MDD were randomized 1:1 to receive either prolonged-release trazodone (150-450 mg) or placebo treatment for 6 weeks. The primary efficacy measurement was the change of the 17-item Hamilton Depression Rating Scale (HAMD-17) total score from baseline to the end of the study. The secondary efficacy measurements were the response and remission rates, the Clinical Global Impression - Improvement of Illness (CGI-I) score at the end of the study, and the change of the HAMD-14 total score and quality of sleep [evaluated by the Pittsburgh Sleep Quality Index (PSQI) scale] during the study period. RESULTS: The mean maximum daily dose was 273.11 mg for the trazodone group and 290.92 mg for the placebo group. At the end of the study, there was a significant difference between the two groups in the HAMD-17 change score (trazodone vs. placebo: -11.07 vs. -8.29, p < 0.001). Trazodone showed advantages at 1 week of treatment, and the effect lasted until the end of the study (week 6). The response and remission rates of the trazodone group were significantly higher than those in the placebo group (response rate: 59.6 vs. 37.2%, p < 0.001; remission rate: 35.5 vs. 22.2%, p = 0.005). The majority of the adverse reactions of trazodone were mild to moderate, and the most frequent adverse reactions (≥5%) were dizziness, dry mouth, somnolence, and nausea. CONCLUSIONS: Prolonged-release trazodone was more effective than placebo in MDD and was well tolerated.

The gut microbiome from middle-aged women with depression modulates depressive-like behaviors and plasma fatty acid metabolism in female middle-aged mice.

BACKGROUND: Intestinal dysbacteriosis has frequently been involved in the context of depression. Nonetheless, only scant information is available about the features and functional changes of gut microbiota in female middle-aged depression (MAD). OBJECTIVE: This study aims to explore whether there are characteristic changes in the gut microbes of female MAD and whether these changes are associated with depressive-like behaviors. Meanwhile, this study observed alterations in the lipid metabolism function of gut microbes and further examined changes in plasma medium- and long-chain fatty acids (MLCFAs) in mice that underwent fecal microbiota transplantation (FMT). METHODS: Stool samples obtained from 31 MAD, along with 24 healthy individuals (HC) were analyzed by 16 S rRNA gene sequencing. Meanwhile, 14-month-old female C57BL/6J mice received antibiotic cocktails and then oral gavage of the microbiota suspension of MAD or HC for 3 weeks to reconstruct gut microbiota. The subsequent depressive-like behaviors, the composition of gut microbiota, as well as MLCFAs in the plasma were evaluated. RESULTS: A noteworthy disruption in gut microbial composition in MAD individuals compared to HC was observed. Several distinct bacterial taxa, including Dorea, Butyricicoccus, and Blautia, demonstrated associations with the demographic variables. A particular microbial panel encompassing 49 genera effectively differentiated MAD patients from HC (AUC = 0.82). Fecal microbiome transplantation from MAD subjects led to depressive-like behaviors and dysfunction of plasma MLCFAs in mice. CONCLUSIONS: These findings suggest that microbial dysbiosis is linked to the pathogenesis of MAD, and its role may be associated with the regulation of MLCFAs metabolism.

The Role of Total White Blood Cell Count in Antipsychotic Treatment for Patients with Schizophrenia.

BACKGROUND: Total white blood cell count (TWBCc), an index of chronic and low-grade inflammation, is associated with clinical symptoms and metabolic alterations in patients with schizophrenia. The effect of antipsychotics on TWBCc, predictive values of TWBCc for drug response, and role of metabolic alterations require further study. METHODS: Patients with schizophrenia were randomized to monotherapy with risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone, perphenazine or haloperidol in a 6-week pharmacological trial. We repeatedly measured clinical symptoms, TWBCc, and metabolic measures (body mass index, blood pressure, waist circumference, fasting blood lipids and glucose). We used mixed-effect linear regression models to test whether TWBCc can predict drug response. Mediation analysis to investigate metabolic alteration effects on drug response. RESULTS: At baseline, TWBCc was higher among patients previously medicated. After treatment with risperidone, olanzapine, quetiapine, perphenazine, and haloperidol, TWBCc decreased significantly (p < 0.05). Lower baseline TWBCc predicted greater reductions in Positive and Negative Syndrome Scale (PANSS) total and negative scores over time (p < 0.05). We found significant mediation of TWBCc for effects of waist circumference, fasting low-density lipoprotein cholesterol, and glucose on reductions in PANSS total scores and PANSS negative subscale scores (p < 0.05). CONCLUSION: TWBCc is affected by certain antipsychotics among patients with schizophrenia, with decreases observed following short-term, but increases following long-term treatment. TWBCc is predictive of drug response, with lower TWBCc predicting better responses to antipsychotics. It also mediates the effects of certain metabolic measures on improvement of negative symptoms. This indicates that the metabolic state may affect clinical manifestations through inflammation.

Paroxetine up-regulates neurogenesis in hippocampus-derived neural stem cell from fetal rats.

Paroxetine is a widely used antidepressant in clinic. Besides its role in inhibition of serotonin reuptake, resent studies indicate that the increase of hippocampal neurogenesis is also involved in its pharmacology. However, only limited data are available in this regard and its effect on the hippocampus-derived neural stem cell (NSCs) has not been well elucidated. In present study, we utilized hippocampus-derived NSCs from fetal rats to investigate the direct effect of paroxetine on the neurogenesis of NSCs and explore the possible cellular and molecular mechanisms. The results showed that paroxetine not only promoted the proliferation of NSCs, but also promoted NSCs to differentiate into neurons other than glial cells. In addition, the elevated protein levels of phosphorylated ERK1/2, Bcl-2, and brain-derived neurotrophic factor were also observed after paroxetine was administered. Furthermore, the proliferative effect and promotion of NSCs differentiating predominantly into neurons of paroxetine was inhibited by U0126, an ERK1/2 phosphorylation inhibitor. In conclusion, these data indicate that paroxetine can promote neurogenesis of neural stem cells, and this effect might be mediated by ERK1/2 signal pathways.

[Influence of coping style and social support on quality of life in patients with impaired glucose tolerance].

OBJECTIVE: To explore how coping style and social support influence the quality of life in patients with impaired glucose tolerance, which act respectively as the internal and external mediating ways. METHODS: A total of 283 patients with impaired glucose tolerance from 6 Three-A hospitals in China were surveyed with self-rating anxiety scale, self-rating depression scale, trait coping style questionnaire, social support scale, and WHOQOL-BREF. RESULTS: Biographic data failed to predict the quality of life in patients with impaired glucose tolerance, while anxiety, depression, social support and coping style significantly influenced their quality of life. CONCLUSION: The fact that emotional disorder, social support and coping style influence the quality of life in patients with type 2 diabetes also exists in patients with impaired glucose tolerance.

Effects of low-frequency rTMS combined with risperidone on the gut microbiome in hospitalized patients with chronic schizophrenia.

Repetitive transcranial magnetic stimulation (rTMS) has been widely used in treating schizophrenia (SCH). However, the effects of the low frequency of rTMS combined with antipsychotics on the gut microbiome in chronic SCH have been poorly investigated. In the present study, psychiatric symptoms were assessed and the stool samples obtained from 33 adult patients with chronic SCH (at baselinephase), 27 after 2 weeks of treatment (rTMS combined with risperidone, SCH-2W), and 37 healthy controls (HC) were analyzed by 16S rRNA gene sequencing. We found that the reduction of phylum Proteobacteria, family Enterobacteriaceae and genera Escherichia-Shigella as well as the increase of genera norank_f_Lachnospiraceae might be related to the antipsychotic effect of rTMS combined with risperidone. These findings indicate that the brain-gut-microbiota axis might be involved in the therapeutic effect of rTMS combined with antipsychotic drugs.