Mitochondrial Biomarkers and Metabolic Syndrome in Bipolar Disorder.

The object of this study is test whether mitochondrial blood-based biomarkers are associated with markers of metabolic syndrome in bipolar disorder, hypothesizing higher lactate but unchanged cell-free circulating mitochondrial DNA levels in bipolar disorder patients with metabolic syndrome. In a cohort study, primary testing from the FondaMental Advanced Centers of Expertise for bipolar disorder (FACE-BD) was conducted, including 837 stable bipolar disorder patients. The I-GIVE validation cohort consists of 237 participants: stable and acute bipolar patients, non-psychiatric controls, and acute schizophrenia patients. Multivariable regression analyses show significant lactate association with triglycerides, fasting glucose and systolic and diastolic blood pressure. Significantly higher levels of lactate were associated with presence of metabolic syndrome after adjusting for potential confounding factors. Mitochondrial-targeted metabolomics identified distinct metabolite profiles in patients with lactate presence and metabolic syndrome, differing from those without lactate changes but with metabolic syndrome. Circulating cell-free mitochondrial DNA was not associated with metabolic syndrome. This thorough analysis mitochondrial biomarkers indicate the associations with lactate and metabolic syndrome, while showing the mitochondrial metabolites can further stratify metabolic profiles in patients with BD. This study is relevant to improve the identification and stratification of bipolar patients with metabolic syndrome and provide potential personalized-therapeutic opportunities.

Mitochondrion-targeted RNA therapies as a potential treatment strategy for mitochondrial diseases.

Mitochondrial diseases are one of the largest groups of neurological genetic disorders. Despite continuous efforts of the scientific community, no cure has been developed, and most treatment strategies rely on managing the symptoms. After the success of coronavirus disease 2019 (COVID-19) mRNA vaccines and accelerated US Food and Drug Administration (FDA) approval of four new RNAi drugs, we sought to investigate the potential of mitochondrion-targeting RNA-based therapeutic agents for treatment of mitochondrial diseases. Here we describe the causes and existing therapies for mitochondrial diseases. We then detail potential RNA-based therapeutic strategies for treatment of mitochondrial diseases, including use of antisense oligonucleotides (ASOs) and RNAi drugs, allotopic therapies, and RNA-based antigenomic therapies that aim to decrease the level of deleterious heteroplasmy in affected tissues. Finally, we review different mechanisms by which RNA-based therapeutic agents can be delivered to the mitochondrial matrix, including mitochondrion-targeted nanocarriers and endogenous mitochondrial RNA import pathways.

Evaluation of postmortem microarray data in bipolar disorder using traditional data comparison and artificial intelligence reveals novel gene targets.

Large-scale microarray studies on post-mortem brain tissues have been utilized to investigate the complex molecular pathology of bipolar disorder. However, a major challenge in characterizing the dysregulation of gene expression in patients with bipolar disorder includes the lack of convergence between different studies, limiting comprehensive understanding from individual results. In this study, we aimed to identify genes that are both validated in published literature and are important classification features of unsupervised machine learning analysis of Stanley Brain Bank microarray database, followed by augmented intelligence method to identify distinct patient molecular subgroups. Through combining traditional literature approaches and machine learning, we identified TBL1XR1, SMARCA2, and CHMP5 to be replicated in 3 of the 4 studies included our analysis. The expression of these genes segregated unique subgroups of patients with bipolar disorder. Our study suggests the involvement of PPARγ pathway regulation in patients with bipolar disorder.

Association of Multivitamin and Mineral Supplementation and Risk of Cardiovascular Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Multiple studies have attempted to identify the association between multivitamin/mineral (MVM) supplementation and cardiovascular disease (CVD) outcomes, but the benefits remain controversial. We performed a systematic review and meta-analysis of the associations between MVM supplementation and various CVD outcomes, including coronary heart disease (CHD) and stroke. METHODS AND RESULTS: We conducted a comprehensive search of Medline, Embase, and the Cochrane Library for studies published between January 1970 and August 2016. We included clinical trials and prospective cohort studies in the general population evaluating associations between MVM supplementation and CVD outcomes. Data extraction and quality assessment were independently conducted by 2 authors, and a third author resolved discrepancies. Eighteen studies with 2 019 862 participants and 18 363 326 person-years of follow-up were included in the analysis. Five studies specified the dose/type of MVM supplement and the rest did not. Overall, there was no association between MVM supplementation and CVD mortality (relative risk [RR], 1.00; 95% confidence interval [CI], 0.97-1.04), CHD mortality (RR, 1.02; 95% CI, 0.92-1.13), stroke mortality (RR, 0.95; 95% CI, 0.82-1.09), or stroke incidence (RR, 0.98; 95% CI, 0.91-1.05). There was no association between MVM supplements and CVD or CHD mortality in prespecified subgroups categorized by mean follow-up period, mean age, period of MVM use, sex, type of population, exclusion of patients with history of CHD, and adjustment for diet, adjustment for smoking, adjustment for physical activity, and study site. In contrast, MVM use did seem to be associated with a lower risk of CHD incidence (RR, 0.88; 95% CI, 0.79-0.97). However, this association did not remain significant in the pooled subgroup analysis of randomized controlled trials (RR, 0.97; 95% CI, 0.80-1.19). CONCLUSIONS: Our meta-analysis of clinical trials and prospective cohort studies demonstrates that MVM supplementation does not improve cardiovascular outcomes in the general population.