{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T18:02:08Z","timestamp":1793296928478,"version":"4.5.0"},"posted":{"date-parts":[[2023,9,14]]},"group-title":"Neuroscience","reference-count":72,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,9,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Our results show a trending increase in mtDNAcn in patients with MDD, which reaches significance when one study with outlying demographic characteristics is excluded. Overall, there was no effect of BD on mtDNAcn, however, further subgroup and meta-regression analysis indicated the effects on mtDNAcn are dependent on BD type.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Together our data suggest whole blood\/leukocyte 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. Further study of blood mtDNAcn could predict downstream health outcomes or treatment responsivity in individuals with mood disorders.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2023.09.13.557572","type":"posted-content","created":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T21:50:17Z","timestamp":1694728217000},"source":"Crossref","is-referenced-by-count":3,"title":["Whole blood mitochondrial copy number in clinical populations with mood disorders: a meta-analysis"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0138-3141","authenticated-orcid":false,"given":"Cali A.","family":"Calarco","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swarnapali M.","family":"Keppetipola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gautam","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2819-4276","authenticated-orcid":false,"given":"Andrea G.","family":"Shipper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9419-2079","authenticated-orcid":false,"given":"Mary Kay","family":"Lobo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2023091903350825000_2023.09.13.557572v1.1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2018.00410"},{"key":"2023091903350825000_2023.09.13.557572v1.2","first-page":"4715","article-title":"Mitochondrial Alterations and Neuropsychiatric Disorders","volume":"18","year":"2012","journal-title":"Curr Med Chem"},{"key":"2023091903350825000_2023.09.13.557572v1.3","doi-asserted-by":"crossref","first-page":"104632","DOI":"10.1016\/j.psyneuen.2020.104632","article-title":"Molecular markers of neuroendocrine function and mitochondrial biogenesis associated with early life stress","volume":"116","year":"2020","journal-title":"Psychoneuroendocrinology"},{"key":"2023091903350825000_2023.09.13.557572v1.4","first-page":"1","article-title":"Dysfunctional mitochondrial processes contribute to energy perturbations in the brain and neuropsychiatric symptoms","volume":"13","year":"2023","journal-title":"Front Pharmacol"},{"key":"2023091903350825000_2023.09.13.557572v1.5","doi-asserted-by":"publisher","DOI":"10.1097\/PSY.0000000000000545"},{"key":"2023091903350825000_2023.09.13.557572v1.6","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.yfrne.2018.01.001","article-title":": An energetic view of stress: Focus on mitochondria","volume":"49","year":"2018","journal-title":"Front Neuroendocrinol"},{"key":"2023091903350825000_2023.09.13.557572v1.7","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.cophys.2018.02.006","article-title":"Mitochondrial dynamics and metabolic homeostasis","volume":"3","year":"2018","journal-title":"Curr Opin Physiol"},{"key":"2023091903350825000_2023.09.13.557572v1.8","doi-asserted-by":"publisher","DOI":"10.1097\/FBP.0000000000000505"},{"key":"2023091903350825000_2023.09.13.557572v1.9","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.brainresbull.2022.01.009","article-title":"Repeated social defeat stress inhibits development of hippocampus neurons through mitophagy and autophagy","volume":"182","year":"2022","journal-title":"Brain Res Bull"},{"key":"2023091903350825000_2023.09.13.557572v1.10","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.bbr.2017.04.022","article-title":"Major depressive disorder mediates accelerated aging in rats subjected to chronic mild stress","volume":"329","year":"2017","journal-title":"Behav Brain Res"},{"key":"2023091903350825000_2023.09.13.557572v1.11","doi-asserted-by":"crossref","first-page":"100634","DOI":"10.1016\/j.jadr.2023.100634","article-title":"Inflammation and mitochondrial dysfunction in affective disorders-novel understandings, novel treatments?","volume":"14","year":"2023","journal-title":"J Affect Disord Reports"},{"key":"2023091903350825000_2023.09.13.557572v1.12","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-59121-0"},{"key":"2023091903350825000_2023.09.13.557572v1.13","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2017.48"},{"key":"2023091903350825000_2023.09.13.557572v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2016.06.040"},{"key":"2023091903350825000_2023.09.13.557572v1.15","doi-asserted-by":"crossref","first-page":"121922","DOI":"10.1016\/j.lfs.2023.121922","article-title":"Manipulating mitochondrial dynamics in the NTS prevents diet-induced deficits in brown fat morphology and activity","volume":"328","year":"2023","journal-title":"Life Sci"},{"key":"2023091903350825000_2023.09.13.557572v1.16","doi-asserted-by":"publisher","DOI":"10.1080\/15622975.2016.1197423"},{"key":"2023091903350825000_2023.09.13.557572v1.17","doi-asserted-by":"publisher","DOI":"10.1007\/s10863-014-9584-6"},{"key":"2023091903350825000_2023.09.13.557572v1.18","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.pnpbp.2017.06.036","article-title":"The interplay between inflammation, oxidative stress, DNA damage, DNA repair and mitochondrial dysfunction in depression","volume":"80","year":"2018","journal-title":"Prog Neuro-Psychopharmacology Biol Psychiatry"},{"key":"2023091903350825000_2023.09.13.557572v1.19","first-page":"1","article-title":"Mitochondria DNA copy number, mitochondria DNA total somatic deletions, Complex I activity, synapse number, and synaptic mitochondria number are altered in schizophrenia and bipolar disorder","volume":"12","year":"2022","journal-title":"Transl Psychiatry"},{"key":"2023091903350825000_2023.09.13.557572v1.20","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.jad.2015.05.060","article-title":"Mitochondrial complex I and III mRNA levels in bipolar disorder","volume":"184","year":"2015","journal-title":"J Affect Disord"},{"key":"2023091903350825000_2023.09.13.557572v1.21","doi-asserted-by":"publisher","DOI":"10.1111\/acps.12417"},{"key":"2023091903350825000_2023.09.13.557572v1.22","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2020.00164"},{"key":"2023091903350825000_2023.09.13.557572v1.23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mito.2021.06.010","article-title":": Blood Mitochondrial DNA Copy Number: What Are We Counting?","volume":"60","year":"2021","journal-title":"Mitochondrion"},{"key":"2023091903350825000_2023.09.13.557572v1.24","doi-asserted-by":"publisher","DOI":"10.1101\/gr.269381.120"},{"key":"2023091903350825000_2023.09.13.557572v1.25","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.mito.2021.10.008","article-title":": Blood biomarkers for assessment of mitochondrial dysfunction: An expert review","volume":"62","year":"2022","journal-title":"Mitochondrion"},{"key":"2023091903350825000_2023.09.13.557572v1.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2020.06.004"},{"key":"2023091903350825000_2023.09.13.557572v1.27","doi-asserted-by":"publisher","DOI":"10.1016\/S1673-8527(08)60099-5"},{"key":"2023091903350825000_2023.09.13.557572v1.28","first-page":"1","article-title":"Characterization of mitochondrial DNA quantity and quality in the human aged and Alzheimer\u2019s disease brain","volume":"16","year":"2021","journal-title":"Mol Neurodegener"},{"key":"2023091903350825000_2023.09.13.557572v1.29","doi-asserted-by":"crossref","first-page":"405","DOI":"10.4103\/1673-5374.379045","article-title":"Mitochondrial DNA methylation and mitochondria-related epigenetics in neurodegeneration","volume":"19","year":"2024","journal-title":"Neural Regen Res"},{"key":"2023091903350825000_2023.09.13.557572v1.30","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-23276-8"},{"key":"2023091903350825000_2023.09.13.557572v1.31","doi-asserted-by":"crossref","first-page":"112831","DOI":"10.1016\/j.ecoenv.2021.112831","article-title":"Decreased mitochondrial DNA copy number in nerve cells and the hippocampus during nicotine exposure is mediated by autophagy","volume":"226","year":"2021","journal-title":"Ecotoxicol Environ Saf"},{"key":"2023091903350825000_2023.09.13.557572v1.32","doi-asserted-by":"publisher","DOI":"10.4161\/auto.25468"},{"key":"2023091903350825000_2023.09.13.557572v1.33","doi-asserted-by":"crossref","unstructured":"Caspani G , Seb\u0151k V , Sultana N , Swann JR , Bailey A (2021): Metabolic phenotyping of opioid and psychostimulant addiction: A novel approach for biomarker discovery and biochemical understanding of the disorder. Br J Pharmacol 1\u201329.","DOI":"10.1111\/bph.15475"},{"key":"2023091903350825000_2023.09.13.557572v1.34","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.psychres.2018.08.014","article-title":": Mitochondrial DNA copy number of peripheral blood in bipolar disorder: The present study and a meta-analysis","volume":"269","year":"2018","journal-title":"Psychiatry Res"},{"key":"2023091903350825000_2023.09.13.557572v1.35","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1080\/15622975.2021.1938214","article-title":": Circulating cell-free mitochondrial DNA in brain health and disease: A systematic review and meta-analysis","volume":"23","year":"2022","journal-title":"World J Biol Psychiatry"},{"key":"2023091903350825000_2023.09.13.557572v1.36","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1080\/15622975.2019.1588993","article-title":"Mitochondrial DNA copy number, damage, repair and degradation in depressive disorder","volume":"21","year":"2020","journal-title":"World J Biol Psychiatry"},{"key":"2023091903350825000_2023.09.13.557572v1.37","first-page":"2009","article-title":"Leukocyte mitochondrial DNA (mtDNA) content is associated with depression in old women","volume":"53","year":"2011","journal-title":"Arch Gerontol Geriatr"},{"key":"2023091903350825000_2023.09.13.557572v1.38","doi-asserted-by":"crossref","first-page":"110656","DOI":"10.1016\/j.pnpbp.2022.110656","article-title":"Whole blood mitochondrial DNA copy number in depression and response to electroconvulsive therapy","volume":"121","year":"2023","journal-title":"Prog Neuro-Psychopharmacology Biol Psychiatry"},{"key":"2023091903350825000_2023.09.13.557572v1.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2015.03.008"},{"key":"2023091903350825000_2023.09.13.557572v1.40","unstructured":"Higgins J , Thomas J, J C , Cumpston M , Li T , Page M , Welch V (Eds.) (2022): Cochrane Handbook for Systematic Reviews of Interventions, 6.3. Cochrane. Retrieved from www.training.cochrane.org\/handbook"},{"key":"2023091903350825000_2023.09.13.557572v1.41","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2288-14-1"},{"key":"2023091903350825000_2023.09.13.557572v1.42","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v036.i11"},{"key":"2023091903350825000_2023.09.13.557572v1.43","doi-asserted-by":"publisher","DOI":"10.1186\/S12888-018-1736-5"},{"key":"2023091903350825000_2023.09.13.557572v1.44","doi-asserted-by":"publisher","DOI":"10.1111\/pcn.12163"},{"key":"2023091903350825000_2023.09.13.557572v1.45","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.pnpbp.2013.09.002","article-title":"Leukocyte mitochondrial DNA copy number in bipolar disorder","volume":"48","author":"45","year":"2014","journal-title":"Prog Neuro-Psychopharmacology Biol Psychiatry"},{"key":"2023091903350825000_2023.09.13.557572v1.46","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.jpsychires.2020.11.016","article-title":"Differences in mitochondrial DNA copy number between patients with bipolar I and II disorders","volume":"145","year":"2022","journal-title":"J Psychiatr Res"},{"key":"2023091903350825000_2023.09.13.557572v1.47","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0131080"},{"key":"2023091903350825000_2023.09.13.557572v1.48","doi-asserted-by":"publisher","DOI":"10.1038\/srep41926"},{"key":"2023091903350825000_2023.09.13.557572v1.49","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-017-3899-8"},{"key":"2023091903350825000_2023.09.13.557572v1.50","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-014-1458-9"},{"key":"2023091903350825000_2023.09.13.557572v1.51","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwv175"},{"key":"2023091903350825000_2023.09.13.557572v1.52","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-017-0048-8"},{"key":"2023091903350825000_2023.09.13.557572v1.53","doi-asserted-by":"crossref","first-page":"105993","DOI":"10.1016\/j.psyneuen.2022.105993","article-title":"Mitochondrial DNA as a marker for treatment-response in post-traumatic stress disorder","volume":"148","year":"2023","journal-title":"Psychoneuroendocrinology"},{"key":"2023091903350825000_2023.09.13.557572v1.54","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.pnpbp.2015.06.012","article-title":"Mitochondrial DNA copy number is reduced in male combat veterans with PTSD","volume":"64","year":"2016","journal-title":"Prog Neuro-Psychopharmacology Biol Psychiatry"},{"key":"2023091903350825000_2023.09.13.557572v1.55","doi-asserted-by":"publisher","DOI":"10.1097\/PSY.0000000000000544"},{"key":"2023091903350825000_2023.09.13.557572v1.56","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2015.04.002"},{"key":"2023091903350825000_2023.09.13.557572v1.57","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2014.12.025"},{"key":"2023091903350825000_2023.09.13.557572v1.58","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-017-0001-9"},{"key":"2023091903350825000_2023.09.13.557572v1.59","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2021.04.002"},{"key":"2023091903350825000_2023.09.13.557572v1.60","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2020.00164"},{"key":"2023091903350825000_2023.09.13.557572v1.61","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1159\/000515594","article-title":": Neuroinflammation in Mood Disorders: Role of Regulatory Immune Cells","volume":"28","year":"2021","journal-title":"Neuroimmunomodulation"},{"key":"2023091903350825000_2023.09.13.557572v1.62","first-page":"1","article-title":"Inflammation as a treatment target in mood disorders: review","volume":"6","year":"2020","journal-title":"BJPsych Open"},{"key":"2023091903350825000_2023.09.13.557572v1.63","doi-asserted-by":"crossref","first-page":"112616","DOI":"10.1016\/j.psychres.2019.112616","article-title":"Investigation of mitochondrial DNA copy number in patients with major depressive disorder","volume":"282","year":"2019","journal-title":"Psychiatry Res"},{"key":"2023091903350825000_2023.09.13.557572v1.64","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-021-01508-2"},{"key":"2023091903350825000_2023.09.13.557572v1.65","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0089680"},{"key":"2023091903350825000_2023.09.13.557572v1.66","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2019.00408"},{"key":"2023091903350825000_2023.09.13.557572v1.67","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.bbi.2021.09.003","article-title":"Low peripheral mitochondrial DNA copy number during manic episodes of bipolar disorders is associated with disease severity and inflammation","volume":"98","year":"2021","journal-title":"Brain Behav Immun"},{"key":"2023091903350825000_2023.09.13.557572v1.68","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1093\/ijnp\/pyab095","article-title":"Mitochondrial DNA Copy Number Is Associated With Treatment Response and Cognitive Function in Euthymic Bipolar Patients Receiving Valproate","volume":"25","year":"2022","journal-title":"Int J Neuropsychopharmacol"},{"key":"2023091903350825000_2023.09.13.557572v1.69","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1111\/bdi.12640","article-title":"Plasma glutathione suggests oxidative stress is equally present in early- and late-onset bipolar disorder","volume":"21","year":"2019","journal-title":"Bipolar Disord"},{"key":"2023091903350825000_2023.09.13.557572v1.70","first-page":"1","article-title":"Telomere length and mitochondrial DNA copy number in bipolar disorder: identification of a subgroup of young individuals with accelerated cellular aging","volume":"12","year":"2022","journal-title":"Transl Psychiatry"},{"key":"2023091903350825000_2023.09.13.557572v1.71","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp051"},{"key":"2023091903350825000_2023.09.13.557572v1.72","doi-asserted-by":"publisher","DOI":"10.1038\/tpj.2009.12"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2023.09.13.557572","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T05:13:49Z","timestamp":1768454029000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2023.09.13.557572"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,14]]},"references-count":72,"URL":"https:\/\/doi.org\/10.1101\/2023.09.13.557572","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1016\/j.psychres.2023.115662","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2023,9,14]]},"subtype":"preprint"}}