Whole blood mitochondrial copy number in clinical populations with mood disorders: A meta-analysis Blood mitochondrial copy number and mood disorders

Major depressive disorder (MDD) and bipolar disorder (BD), are globally prevalent, contributing to significant disease burden and adverse health outcomes. These mood disorders are associated with changes in many aspects of brain reward pathways, yet cellular and molecular changes in the brain are not readily available in clinical populations. Therefore, the use of biomarkers as proxies for changes in the brain are necessary. The proliferation of mitochondria in blood has emerged as a potentially useful biomarker, yet a clear consensus on how these mood disorders impact mitochondrial DNA copy number (mtDNAcn) has not been reached. To determine the current available consensus on the relationship of mood disorder diagnosis and blood mtDNcn, we performed a meta-analysis of available literature measuring this biomarker. Following PRISMA guidelines for a systematic search, 22 papers met inclusion criteria for meta-analysis (10 MDD, 10 BD, 2 both MDD and BD). We extracted demographic, disorder, and methodological information with mtDNAcn. Using the metafor package for R, calculated effect sizes were used in random effects or meta regression models for MDD and BD. Overall, our data suggest blood mtDNAcn may be a useful biomarker for mood disorders, with MDD and BD Type II associated with higher mtDNAcn, and BD Type I associated with lower mtDNAcn. Initially, we observed a trending increase in mtDNAcn in patients with MDD, which reached significance when one study with outlying demographic char-acteristics was excluded. Subgroup and meta-regression analysis indicated the relationship between mtDNAcn and diagnosis in patients with BD is dependent on BD type, while no relationship is detectable when BD types are mixed. Further study of blood mtDNAcn could predict downstream health outcomes or treatment responsivity in individuals with mood disorders.