Efficacy and acceptability of anti-inflammatory agents in major depressive disorder: a systematic review and meta-analysis.

Background: Anti-inflammatory agents have emerged as a potential new therapy for major depressive disorder (MDD). In this meta-analysis, our aim was to evaluate the antidepressant effect of anti-inflammatory agents and compare their efficacy. Methods: We conducted a comprehensive search across multiple databases, including PubMed, Embase, Web of Science, Cochrane Review, Cochrane Trial, and ClinicalTrials.gov, to identify eligible randomized clinical trials. The primary outcome measures of our meta-analysis were efficacy and acceptability, while the secondary outcome measures focused on remission rate and dropout rate due to adverse events. We used odds ratio (OR) and 95% confidence interval (95% CI) to present our results. Results: A total of 48 studies were included in our analysis. In terms of efficacy, anti-inflammatory agents demonstrated a significant antidepressant effect compared to placebo (OR = 2.04, 95% CI: 1.41-2.97, p = 0.0002). Subgroup analyses revealed that anti-inflammatory agents also exhibited significant antidepressant effects in the adjunctive therapy subgroup (OR = 2.17, 95% CI: 1.39-3.37, p = 0.0006) and in MDD patients without treatment-resistant depression subgroup (OR = 2.33, 95% CI: 1.53-3.54, p < 0.0001). Based on the surface under the cumulative ranking curve (SUCRA) value of network meta-analysis, nonsteroidal anti-inflammatory drugs (NSAIDs) (SUCRA value = 81.6) demonstrated the highest acceptability among the included anti-inflammatory agents. Conclusion: In summary, our meta-analysis demonstrates that anti-inflammatory agents have significant antidepressant effects and are well-accepted. Furthermore, adjunctive therapy with anti-inflammatory agents proved effective in treating MDD. Among the evaluated anti-inflammatory agents, NSAIDs exhibited the highest acceptability, although its efficacy is comparable to placebo. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=422004), identifier CRD42023422004.

Side effects and cognitive benefits of buspirone: A systematic review and meta-analysis.

Buspirone, a 5-hydroxytryptamine 1A (5-HT1A) receptor agonist, has been investigated for its use in various diseases. However, knowledge about its side effects and potential cognitive benefits in different conditions is limited. Cognitive impairment is also a prevalent symptom in many diseases, yet effective treatments are still lacking. Therefore, to explore the potential side effects of buspirone and the possible cognitive benefits of buspirone, we conducted a comprehensive search of several databases, including PubMed, Embase, Web of Science, Cochrane Review, Cochrane Trial, and ClinicalTrials.gov, to identify eligible randomized clinical trials. Our primary outcome measures included both side effects (adverse events) and cognitive benefits. For continuous variables, we utilized effect size with a 95% confidence interval (CI), whereas for dichotomous variables, we used odds ratios (OR) with a 95% CI. In total, 16 studies were included in this analysis, with 13 studies reporting on buspirone's side effects and 4 studies focusing on cognitive tasks. In terms of side effects, buspirone exhibited a higher rate of dizziness (OR = 4.66, 95% CI: 2.07-10.47), constipation (OR = 4.11, 95% CI: 1.34-12.55), and gastric distress (OR = 1.97, 95% CI: 1.03-3.78) than the placebo group. Regarding cognitive functions, buspirone showed significant benefits (g = 0.20, 95% CI: 0.06-0.34) while the placebo did not. Subgroup analysis indicated superior performance in visual learning and memory (g = 0.49, 95% CI: 0.21-0.78), logical reasoning (g = 0.42, 95% CI: 0.14-0.71), and attention (g = 0.37, 95% CI: 0.13-0.61) when compared to placebo. Our findings indicated that participants in the buspirone group experienced side effects of dizziness, constipation, and gastric distress in different diseases. Despite these adverse events, however, buspirone demonstrated significant cognitive benefits, particularly in the domains of visual learning and memory, logical reasoning, and attention.

The impact of childhood trauma on emotional distress and the moderating role of sense of coherence among college students in China.

Childhood trauma is strongly linked to emotional distress. However, few studies have explored the impact of sense of coherence (SOC) on the relationship between childhood trauma and emotional distress in college students. This study aimed to explore its impact on the relationship between childhood trauma and emotional distress. Analyzing data from 2307 Chinese college students, we found that SOC moderated the association between childhood trauma and anxiety/depression levels. Females showed higher SOC and lower anxiety/depression despite experiencing more childhood trauma. Multiple linear regression revealed that anxiety was negatively associated with SOC(P < 0.001) and grade(P = 0.027), and positively with childhood trauma(P < 0.001) and male gender(P = 0.004). Similarly, the depression exhibited similar associations. SOC moderated negatively the relationship between CTQ and anxiety, as well as between CTQ and depression. Childhood trauma is associated with increased emotional distress risk among college students, but a strong SOC can reduce this risk.

Abnormal functional connectivity within the prefrontal cortex is associated with multiple plasma lipid species in major depressive disorder.

BACKGROUND: Abnormalities in functional connectivity (FC) in major depressive disorder (MDD) have been widely reported. Analysis of the relationship between FC and plasma lipid profiles would be meaningful in the exploration of pathophysiological mechanisms and helpful for the identification of biomarkers for MDD. METHODS: Patients with MDD (n = 49) and healthy controls (HC, n = 87) were recruited. Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected for FC construction. The plasma lipid profiles were acquired using ultra-performance liquid chromatography (UPLC) and mass spectrometry (MS) analysis and clustered as co-expression modules. The differential FC and lipid modules between HCs and patients with MDD were identified, and then the association between FC and lipid co-expression modules was analyzed using correlation analysis. The modules associated molecular function was explored using metabolite set enrichment analysis (MSEA). RESULTS: MDD-associated FC and lipid co-expression modules were identified. One module was associated with FC values between the right orbital part of the middle frontal gyrus and the opercular part of the left inferior frontal gyrus, which was enriched in lipid sets of diacylglycerols and fatty alcohols; another module was associated with FC values between the right middle frontal gyrus and the right anterior cingulate and paracingulate gyri, which was enriched in lipid sets of glycerophosphocholines and glycerophosphoethanolamines. CONCLUSION: Our results indicated that abnormal FC in the prefrontal cortex is associated with multiple plasma lipid species, which may provide novel clues for exploring the pathophysiology of MDD.

Down-regulated miR-16-2 in peripheral blood is positively correlated with decreased bilateral insula volume in patients with major depressive disorder.

BACKGROUND: The downregulated microRNA-16-2-3p (miR-16-2) had been believed to be associated with major depressive disorder (MDD). This study aimed to investigate the potential of miR-16-2 as a biomarker for MDD by analysing its expression levels, furthermore, to explore the relationship between miR-16-2, clinical symptoms and alterations in grey matter volume (GMV) in MDD patients. METHODS: Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression level of miR-16-2 in 48 drug-naïve patients with MDD and 50 healthy controls (HCs). We conducted ROC curve analysis to assess the diagnostic value of miR-16-2 in MDD, and evaluated its ability to predict antidepressant response by reassessing depressive and anxiety symptoms after treatment. Voxel-based morphometry was carried out to explore alterations in regional GMV that may be associated with MDD. Pearson analysis was used to explore the relationship between miR-16-2 expression, clinical symptoms, and altered GMV in the brains of MDD patients. RESULTS: We found that MDD patients had significantly downregulated miR-16-2 expression, which was negatively correlated with HAMD-17 and HAMA-14 scores, and had great diagnostic value for MDD (AUC = 0.806, 95 % CI: 0.721-0.891). In addition, MDD patients had significantly lower GMV in the bilateral insula and left superior temporal gyrus (STG_L) than HCs. GMV reduction in the bilateral insula was found to be correlated with miR-16-2 expression. CONCLUSIONS: Our findings support the potential value of miRNA-16-2 as a biomarker for MDD. It also suggests that miRNA-16-2 may be associated with abnormal insula and involved in pathophysiological mechanisms of MDD.

Association between genetically determined telomere length and health-related outcomes: A systematic review and meta-analysis of Mendelian randomization studies.

Emerging evidence has shown that leukocyte telomere length (LTL) is associated with various health-related outcomes, while the causality of these associations remains unclear. We performed a systematic review and meta-analysis of current evidence from Mendelian randomization (MR) studies on the association between LTL and health-related outcomes. We searched PubMed, Embase, and Web of Science up to April 2022 to identify eligible MR studies. We graded the evidence level of each MR association based on the results of the main analysis and four sensitive MR methods, MR-Egger, weighted median, MR-PRESSO, and multivariate MR. Meta-analyses of published MR studies were also performed. A total of 62 studies with 310 outcomes and 396 MR associations were included. Robust evidence level was observed for the association between longer LTL and increased risk of 24 neoplasms (the strongest magnitude for osteosarcoma, GBM, glioma, thyroid cancer, and non-GBM glioma), six genitourinary and digestive system outcomes of excessive or abnormal growth, hypertension, metabolic syndrome, multiple sclerosis, and clonal hematopoiesis of indeterminate potential. Robust inverse association was observed for coronary heart disease, chronic kidney disease, rheumatoid arthritis, juvenile idiopathic arthritis, idiopathic pulmonary fibrosis, and facial aging. Meta-analyses of MR studies suggested that genetically determined LTL was associated with 12 neoplasms and 9 nonneoplasm outcomes. Evidence from published MR studies supports that LTL plays a causal role in various neoplastic and nonneoplastic diseases. Further research is required to elucidate the underlying mechanisms and to bring insight into the potential prediction, prevention, and therapeutic applications of telomere length.

Efficacy and acceptability of second-generation antipsychotics with antidepressants in unipolar depression augmentation: a systematic review and network meta-analysis.

Pharmacological treatment of major depressive disorder is often inefficient, and multiple strategies are used for inadequate response to antidepressants. Second-generation antipsychotics are used as augmentation measures in clinical practice; evidence of their efficacy and acceptability is insufficient, and it remains confusing as to which drug should be selected first. In this systematic review and network meta-analysis, we included randomised controlled trials of second-generation antipsychotics used as adjunctive treatment in patients with suboptimal responses. Outcome measures were efficacy (response and remission) and acceptability (dropout due to any reason and adverse events). Thirty-three trials comprising 10 602 participants were included. Regarding efficacy, response rates indicated that all antipsychotics except for ziprasidone were more efficacious than the placebo, with the odds ratios (ORs) ranging from 1.34 for olanzapine and cariprazine [95% credible interval (CrI) 1.04-1.73 and 1.07-1.67, respectively] to 2.17 for risperidone (95% CrI 1.38-3.42). When considering remission, cariprazine was not effective (OR 1.21, 95% CrI 0.96-1.54). For acceptability, quetiapine (OR 0.68, 95% CrI 0.50-0.91), brexpiprazole (OR 0.69, 95% CrI 0.55-0.86), and cariprazine (OR 0.61, 95% CrI 0.46-0.82) were worse than the placebo. With regards to tolerability, only olanzapine (OR 0.51, 95% CrI 0.25-1.07) and risperidone (OR 0.48, 95% CrI 0.10-2.21) showed no significant differences compared with placebo. The administration of adjunctive antipsychotics is associated with high effectiveness and low acceptability. Risperidone and aripiprazole are more efficacious and accepted than other atypical antipsychotics.