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Background Dynamic interpersonal therapy (DIT) is a brief, structured psychodynamic psychotherapy with demonstrated efficacy in treating major depressive disorder (MDD). The aim of the study was to determine whether DIT is an acceptable and efficacious treatment for MDD patients in China. Method Patients were randomized to 16-week treatments with either DIT plus antidepressant medication (DIT + ADM; n = 66), general supportive therapy plus antidepressant medication (GST + ADM; n = 75) or antidepressant medication alone (ADM; n = 70). The Hamilton Depression Rating Scale (HAMD) administered by blind raters was the primary efficacy measure. Assessments were completed during the acute 16-week treatment and up to 12-month posttreatment. Results The group × time interaction was significant for the primary outcome HAMD (F = 2.900, df1 = 10, df2 = 774.72, p = 0.001) in the acute treatment phase. Pairwise comparisons showed a benefit of DIT + ADM over ADM at weeks 12 [least-squares (LS) mean difference = −3.161, p = 0.007] and 16 (LS mean difference = −3.237, p = 0.004). Because of the unexpected high attrition during the posttreatment follow-up phase, analyses of follow-up data were considered exploratory. Differences between DIT + ADM and ADM remained significant at the 1-, 6-, and 12-month follow-up (ps range from 0.001 to 0.027). DIT + ADM had no advantage over GST + ADM during the acute treatment phase. However, at the 12-month follow-up, patients who received DIT remained less depressed. Conclusions Acute treatment with DIT or GST in combination with ADM was similarly efficacious in reducing depressive symptoms and yielded a better outcome than ADM alone. DIT may provide MDD patients with long-term benefits in symptom improvement but results must be viewed with caution.

Na Zhu,1,&ast; WeiHua Zhang,2,&ast; Jia Huang,3 Yousong Su,3 JingFang Lu,3 Lu Yang,3 YiFan Shi,3 ShaoHua Hu,4,&ast; Jun Chen,3,5,&ast; Yiru Fang3,5,6,&ast; 1Department of Psychiatry, Shanghai Pudong New Area Mental Health Center, Tong Ji University School of Medicine, Shanghai, People’s Republic of China; 2Department of Psychiatry, Taizhou Second People’s Hospital, Taizhou, People’s Republic of China; 3Clinical Research Center, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4Department of Psychiatry, First Affiliated Hospital, Zhejiang University School of Medicine, The Key Laboratory of Mental Disorder Management of Zhejiang Province, Hangzhou, People’s Republic of China; 5Shanghai Key Laboratory of Psychotic Disorders, Shanghai, People’s Republic of China; 6State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, CAS, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: ShaoHua Hu; Jun Chen, Email dorhushaohua@zju.edu.cn; doctorcj2010@gmail.comBackground: Cognitive impairment is one of the core features of bipolar depression. A unified, reliable, and valid assessment tool is key to screening and assessing cognitive impairment. The THINC-Integrated Tool (THINC-it) is a simple and quick battery for screening cognitive impairment in patients with major depressive disorder. However, the use of the tool has not been validated in patients with bipolar depression.Methods: The cognitive functions of 120 patients with bipolar depression and 100 healthy controls were evaluated using the THINC-it tool including Spotter, Symbol Check, Codebreaker, Trials, and the only one subjective test (PDQ-5-D) and five corresponding standard tests. A psychometric analysis of the THINC-it tool was performed.Results: The overall Cronbach’s alpha coefficient of the THINC-it tool was 0.815. The intra-group correlation coefficient (ICC) of retest reliability ranged from 0.571 to 0.854 (P< 0.001), while the correlation r of parallel validity ranged from 0.291 to 0.921 (P< 0.001). There were significant differences in the two groups Z-scores of THINC-it total score, Spotter, Codebreaker, Trails, and PDQ-5-D (P< 0.05). Construct validity was analyzed using exploratory factor analysis (EFA). The Kaiser-Meyer-Olkin (KMO) value was 0.749. Using Bartlett’s Sphericity test, the χ2 (10) value was 198.257 (P< 0.001). The factor loading coefficients of Spotter, Symbol Check, Codebreaker, and Trails on the common factor 1 were − 0.724, 0.748, 0.824, and − 0.717, respectively, and the factor loading coefficient of PDQ-5-D on the common factor 2 was 0.957. Results revealed that the correlation coefficient of the two common factors was 0.125.Conclusion: The THINC-it tool has good reliability and validity in assessing patients with bipolar depression.Keywords: bipolar disorder, cognitive impairment, reliability, THINC-it tool, validity

Background: Antipsychotics are known to be associated with metabolic syndromes (MetS). Chlorpromazine (CPZ) and Clozapine (CLZ) are currently the most commonly used antipsychotics in low-income districts of China. However, potential differences in the long-term effects of CPZ and CLZ on MetS in schizophrenia inpatients are not well understood. Here, we aimed to identify any MetS profile differences between long-term schizophrenia patients who were prescribed either CPZ or CLZ at a primary psychiatric hospital. Methods: We recruited a total of 204 male schizophrenia patients who received either CPZ or CLZ. We measured their weight, height, body mass index (BMI), waist circumference (WC), diastolic blood pressure (DBP), and systolic blood pressure (SBP), as well as their biochemical indicators, including fasting blood glucose (FBS), triglycerides (TG), cholesterol (TC), high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c). Results: The MetS prevalence in the CPZ and CLZ groups was 31% and 37.5%, respectively. The CLZ group had significantly higher DBP levels and a higher incidence of dyslipidemia (HDL-c) but lower HDL-c and TC levels than the CPZ group. We also determined that smoking history, BMI, and duration of hospitalisation were risk factors for the development of MetS. Moreover, we found that CPZ and CLZ were correlated with the same risk for developing MetS and that BMI was a vital risk factor of MetS for both the CPZ and CLZ groups. Conclusion: Long-term CPZ and CLZ prescriptions were associated with similar profiles for developing MetS of schizophrenia patients.

Background: Hyodeoxycholic acid (HDCA) is a natural secondary bile acid with enormous pharmacological effects, such as modulating inflammation in neuron. However, whether HDCA could suppress microglial inflammation has not been elucidated yet. Aims: To determine the anti-microglial inflammatory effect of HDCA in lipopolysaccharide (LPS) models and its mechanisms. Methods: The effect of HDCA was evaluated in LPS-stimulated BV2 microglial cells in vitro and the cortex of LPS-treated mice in vivo. Immunohistochemistry and immunofluorescence were used to visualize the localization of nuclear factor kappa light-chain enhancer of activated B cells (NF-κB) and ionized calcium-binding adaptor protein-1 (Iba-1), respectively. The mRNA expression of inflammatory cytokines was measured by RT-qPCR. The protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), takeda G-coupled protein receptor 5 (TGR5), and the phosphorylation of protein kinase B (AKT), NF-κB, and inhibitor of NF-κB protein α (IκBα) was examined by Western blot. Results: HDCA inhibited the inflammatory responses in LPS-treated BV2 cells and in the cortex of LPS-treated mice, evidenced by decreased production of inflammatory mediators such as iNOS, COX-2, tumor necrosis factor (TNF-α), interleukin (IL)-6, and IL-1β. Further study demonstrated that HDCA repressed the phosphorylation, nuclear translocation, and transcriptional activity of NF-κB and inhibited the activation of AKT in BV-2 cells induced by LPS. Meanwhile, addition of TGR5 inhibitor, triamterene, abolished the effects of HDCA on TGR5, AKT, and NF-κB. Conclusion: The present study demonstrated that HDCA prevents LPS-induced microglial inflammation in vitro and in vivo, the action of which is via regulating TGR5/AKT/NF-κB signaling pathway.

Nutritional supplementations have been widely used as adjunctive treatments for schizophrenia. However, among these supplementations, of which the most beneficial is currently unknown. This study aimed to compare and rank the effectiveness of nutritional supplementations in the adjunctive treatments of schizophrenia. The four nutritional supplementations evaluated were: 1) folate acid or vitamin B12; 2) vitamin D; 3) N-acetyl cysteine (NAC); 4) Omega-3 polyunsaturated fatty acid, including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). 17 eligible RCTs with 1165 participants were included in this network meta-analysis based on study criteria. NAC supplementation was significantly more efficacious than folic acid or vitamin B12 [MD (95% CI): -6.6 (-10.8, -2.4)] and omega-3 polyunsaturated fatty acid [MD (95% CI): -5.1(-9.9, -0.8)] supplementation in the term of PANSS score changes. There were no significant differences in the PANSS score changes between NAC and vitamin D [MD (95% CI): -5.2 (-10.9, 0.5)] supplementations. The estimated ranking probabilities of treatments showed that NAC might be the most effective adjunctive intervention over all nutritional supplementations. These results indicate that NAC could improve PANSS score and it may be among the most effective nutritional supplementations in schizophrenia patients.

Background: Most patients with the major depressive disorder (MDD) have varying degrees of impaired social functioning, and functional improvement often lags behind symptomatic improvement. However, it is still unclear if certain neurobiological factors underlie the deficits of social function in MDD. The aim of this study was to investigate the biomarkers of social function in MDD using structural magnetic resonance imaging (MRI). Methods: 3T anatomical MRI was obtained from 272 subjects including 46 high-functioning (high-SF, Sheehan Disability Scale (SDS) rating < 18) and 63 low-functioning (low-SF, SDS score ≥ 18) patients with MDD and 163 healthy controls (HC). Voxel-based morphometry (VBM) was employed to locate brain regions with grey matter (GM) volume differences in relation to social function in MDD. Regions showing GM differences in relation to social function at baseline were followed up longitudinally in a subset of 38 patients scanned after 12-week treatment. Results: Volume of right parahippocampal gyrus (rPHG) was significantly reduced in low-SF patients with MDD when compared to high-SF ones (FDR-corrected p < 0.05). Over 12 weeks of follow-up, though SF improved overall, the high and low-SF subgroups continued to differ in their SF, but had no progressive changes in PHG volume. Limitations: Limited functional assessment, high drop-out rate and median-based grouping method. Conclusions: Greater GM volume (GMV) of the rPHG may mark better social function in patients with MDD.

The relationship between thyroid function and depression has long been recognized, but little is known about the effect of thyroid function on the risk of readmission after hospitalization for major depressive disorder (MDD). This retrospective cohort study was aimed to explore the effect of thyroid function on psychiatric readmission after hospitalization for MDD. Data was derived from electronic medical records (EMR) of the Shanghai Mental Health Center (SMHC), Shanghai, China. Univariate and multivariate logistic regression analyses were conducted in subjects aged ≥ 18 years who had been hospitalized for MDD between January 1, 2007, and May 31, 2019. Of the 1803 eligible patients, 85 and 132 patients experienced psychiatric readmission within 90 days and 180 days after discharge respectively. Multivariate analyses showed that serum FT3 level (aOR=1.271; 95%CI=1.051-1.537) and comorbidity of thyroid disease (aOR=2,179; 95%CI=1.136-4.179) was independently associated with the risk of 90-day and 180-day readmission respectively. These findings indicated that high serum FT3 levels and comorbidity of thyroid disease could increase the risk of readmission after hospitalization for MDD. It is warranted to provide routine assessment and intervention of the thyroid function during the treatment of depression so as to prevent re-hospitalization.