Association between mitochondrial DNA levels and depression: a systematic review and meta-analysis.

BACKGROUND: Mitochondrial dysfunction leading to disturbances in energy metabolism has emerged as one of the risk factors in the pathogenesis of depression. Numerous studies have identified alterations in the content of mitochondrial DNA (mtDNA) in peripheral blood and cerebrospinal fluid of individuals with depression. Researchers have sought to establish a clear association between mtDNA and depression. Consequently, we conducted a comprehensive meta-analysis to assess the existing evidence regarding the impact of mtDNA on depression. METHODS: This study conducted a thorough search of the following databases up to March 13, 2023: PubMed, Embase, the Cochrane Library, the Web of Science, Wanfang Database, SINOMED, the China Science and Technology Journal Database, and China National Knowledge Infrastructure. The meta-analysis was carried out using RevMan (version 5.4) and Stata (version 16.0) software. In addition, publication bias was assessed with funnel plots, Begg's test and Egger's test. RESULTS: Our analysis included data from 10 articles, including 12 studies for further examination. A total of 1400 participants were included in this study, comprising 709 (including 300 males and 409 females) patients with depression and 691 (including 303 males and 388 females) healthy controls. The average age of depressed patients was (42.98 ± 2.55) years, and the average age of healthy people was (41.71 ± 2.6) years. The scales used to assess outcomes are Hamilton-rating scale for Depression(4 articles), Montgomery-Asberg Depression Rating Scale(3 articles), and Mini-Internatioal Neuropsychiatric Interview (1 articles). The meta-analysis revealed significantly higher levels of mtDNA in circulating blood samples and skin fibroblasts of individuals with depression in comparison to healthy controls [standardized mean difference(SMD) = 0.42, 95% confidence intervals(CI): 0.16, 0.67]. CONCLUSIONS: Our study concludes that there is a significant (p < 0.05) increase in mtDNA levels in serum, plasma, and cerebrospinal fluid in individuals with depression. These findings suggest that mtDNA could serve as a potential biomarker for diagnosing depression. REGISTRATION NUMBER: PROSPERO CRD42023414285.

Value of contrast-enhanced MR angiography for the follow-up of treated brain arteriovenous malformations: systematic review and meta-analysis.

OBJECTIVE: To estimate the diagnostic value of contrast-enhanced MR angiography (CE-MRA) in identifying residual brain arteriovenous malformations (AVMs) after treatment. METHODS: We retrieved appropriate references from the electronic databases of PubMed, Web of Science, Embase, and Cochrane Library, and then evaluated the methodology quality of included references using the QUADAS-2 tool. We calculated the pooled sensitivity and specificity by applying a bivariate mixed-effects model and detected the publication bias using Deeks' funnel plot. The values of I2 were used to test heterogeneity and meta-regression analyses were performed to search for the causes of heterogeneity. RESULTS: We included 7 eligible studies containing 223 participants. Compared with a gold standard, the overall sensitivity and specificity of CE-MRA in detecting residual brain AVMs were 0.77 (95% CI 0.65-0.86) and 0.97 (95% CI 0.82-1.00), respectively. Based on the summary ROC curve, the AUC was 0.89 (95% CI 0.86-0.92). Heterogeneity could be observed in our study, especially for the specificity (I2 = 74.23%). Furthermore, there was no evidence of publication bias. CONCLUSIONS: Our study provides evidence that CE-MRA has good diagnostic value and specificity for the follow-up of treated brain AVMs. Nevertheless, considering the small sample size, heterogeneity, and many factors that may affect the diagnostic accuracy, future large-sample, prospective studies are necessary to validate the results. KEY POINTS: • The pooled sensitivity and specificity of contrast-enhanced MR angiography (CE-MRA) in detecting residual arteriovenous malformations (AVMs) were 0.77 (95% CI 0.65-0.86) and 0.97 (95% CI 0.82-1.00). • The four-dimensional CE-MRA showed less sensitivity than the three-dimensional CE-MRA for treated AVMs. • CE-MRA is helpful to identify residual AVMs and reduce excessive DSA during follow-up.

Safety and Efficacy of Edaravone in Patients with Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVE: The efficacy and safety of edaravone for the treatment of amyotrophic lateral sclerosis (ALS) remain unclear. The aim of this meta-analysis was to provide evidence-based medical guidance and advice for the clinical application of edaravone in the treatment of ALS. METHODS: PubMed, Embase, Chinese Biomedical Literature Database (CBM), Cochrane Library and Web of Science were searched through 09 March 2022 for randomized controlled trials (RCTs) on the safety and efficacy of edaravone versus placebo during follow-up of patients with ALS. A summary of the outcome measures with GRADE was performed. This study was registered on PROSPERO (ID: CRD 42022319997). RESULTS: Five RCTs with a total of 566 participants were included, and there was a significant difference (mean difference [MD] 1.33, 95% confidence interval [CI] 0.33-2.34; p = 0.009) in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score between the treatment and placebo groups. The edaravone group had an increased grip strength (MD 0.26, 95% CI 0.03-0.49; p = 0.03) and modified Norris Scale score (MD 2.81, 95% CI 1.18-4.43; p = 0.0007). However, there were no significant differences between groups for the change in forced vital capacity (FVC)% (MD 0.55, 95% CI - 3.15 to 4.24; p = 0.77), pinch strength (MD 0.05, 95% CI - 0.05 to 0.16; p = 0.33) or Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) score (MD - 4.76, 95% CI - 9.56 to 0.03; p = 0.05). The incidence of adverse events (AEs) (risk ratio [RR] 0.09, 95% CI 0.93-1.05; p = 0.65), serious adverse events (SAEs) (RR 0.72, 95% CI 0.52-1.00; p = 0.05) and the number of deaths (risk difference [RD] 0.00, 95% CI - 0.02 to 0.03; p = 0.83) were not statistically different from the placebo group. The quality of evidence was low only for SAEs, and the remaining outcome measures were of moderate quality. CONCLUSIONS: Compared with placebo, edaravone may provide potential clinical benefits in the treatment of ALS and may not increase the number of AEs and deaths. However, due to the low-quality evidence of the included studies and the small sample size, more high-quality and high-standard research evidence is needed to confirm these results. PROTOCOL REGISTRATION: This study was registered on PROSPERO (ID: CRD 42022319997).