Blood-based mitochondrial respiratory chain function in major depression

Abstract Mitochondrial dysfunction has been implicated in major depressive disorder (MDD). A measure of mitochondrial respiratory chain (RC) enzymatic activity—the Mitochondrial Health Index (MHI)—has previously been found to correlate with stress and emotional states in caregivers. We here report m...

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Autores principales:	Johan Fernström, Synthia H. Mellon, Marlon A. McGill, Martin Picard, Victor I. Reus, Christina M. Hough, Jue Lin, Elissa S. Epel, Owen M. Wolkowitz, Daniel Lindqvist
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/bb5e5046f7e5489088c9d6125ed82ea3
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spelling	oai:doaj.org-article:bb5e5046f7e5489088c9d6125ed82ea32021-11-21T12:07:48ZBlood-based mitochondrial respiratory chain function in major depression10.1038/s41398-021-01723-x2158-3188https://doaj.org/article/bb5e5046f7e5489088c9d6125ed82ea32021-11-01T00:00:00Zhttps://doi.org/10.1038/s41398-021-01723-xhttps://doaj.org/toc/2158-3188Abstract Mitochondrial dysfunction has been implicated in major depressive disorder (MDD). A measure of mitochondrial respiratory chain (RC) enzymatic activity—the Mitochondrial Health Index (MHI)—has previously been found to correlate with stress and emotional states in caregivers. We here report mitochondrial RC activities, mitochondrial DNA copy number (mtDNAcn), and the composite MHI in unmedicated and somatically healthy subjects with MDD (n = 47) and healthy controls (HC) (n = 11). We also explore, in a subset of the MDD sample (n = 33), whether these markers are associated with response to 8 weeks of SSRI treatment. Mitochondrial RC complexes I, II, IV, citrate synthase (CS), mtDNAcn, and the MHI were assayed in peripheral blood mononuclear cells. Treatment response was defined as >50% decrease on the 25-item Hamilton Depression Rating Scale (HRDS-25). There were no significant differences in MHI or any of the mitochondrial markers between MDD subjects and HCs. Compared to SSRI nonresponders, SSRI responders had significantly higher baseline mitochondrial content markers CS (p = 0.02) and mtDNAcn (p = 0.02), and higher complex I activity (p = 0.01). Complex II activity increased significantly over treatment, irrespective of clinical response (p = 0.03). Complex I activity decreased in responders (n = 9), but increased in nonresponders (n = 18) (group x time interaction, p = 0.02). Absolute treatment-associated change in HDRS-25 scores correlated significantly with change in complex I activity between baseline and week 8 (r = 0.47, p = 0.01). Although mitochondrial markers did not distinguish MDD from controls, they did distinguish SSRI responders from nonresponders. If larger studies validate these mitochondrial differences, they may become useful biomarkers and identify new drug targets.Johan FernströmSynthia H. MellonMarlon A. McGillMartin PicardVictor I. ReusChristina M. HoughJue LinElissa S. EpelOwen M. WolkowitzDaniel LindqvistNature Publishing GrouparticleNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENTranslational Psychiatry, Vol 11, Iss 1, Pp 1-7 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Johan Fernström Synthia H. Mellon Marlon A. McGill Martin Picard Victor I. Reus Christina M. Hough Jue Lin Elissa S. Epel Owen M. Wolkowitz Daniel Lindqvist Blood-based mitochondrial respiratory chain function in major depression
description	Abstract Mitochondrial dysfunction has been implicated in major depressive disorder (MDD). A measure of mitochondrial respiratory chain (RC) enzymatic activity—the Mitochondrial Health Index (MHI)—has previously been found to correlate with stress and emotional states in caregivers. We here report mitochondrial RC activities, mitochondrial DNA copy number (mtDNAcn), and the composite MHI in unmedicated and somatically healthy subjects with MDD (n = 47) and healthy controls (HC) (n = 11). We also explore, in a subset of the MDD sample (n = 33), whether these markers are associated with response to 8 weeks of SSRI treatment. Mitochondrial RC complexes I, II, IV, citrate synthase (CS), mtDNAcn, and the MHI were assayed in peripheral blood mononuclear cells. Treatment response was defined as >50% decrease on the 25-item Hamilton Depression Rating Scale (HRDS-25). There were no significant differences in MHI or any of the mitochondrial markers between MDD subjects and HCs. Compared to SSRI nonresponders, SSRI responders had significantly higher baseline mitochondrial content markers CS (p = 0.02) and mtDNAcn (p = 0.02), and higher complex I activity (p = 0.01). Complex II activity increased significantly over treatment, irrespective of clinical response (p = 0.03). Complex I activity decreased in responders (n = 9), but increased in nonresponders (n = 18) (group x time interaction, p = 0.02). Absolute treatment-associated change in HDRS-25 scores correlated significantly with change in complex I activity between baseline and week 8 (r = 0.47, p = 0.01). Although mitochondrial markers did not distinguish MDD from controls, they did distinguish SSRI responders from nonresponders. If larger studies validate these mitochondrial differences, they may become useful biomarkers and identify new drug targets.
format	article
author	Johan Fernström Synthia H. Mellon Marlon A. McGill Martin Picard Victor I. Reus Christina M. Hough Jue Lin Elissa S. Epel Owen M. Wolkowitz Daniel Lindqvist
author_facet	Johan Fernström Synthia H. Mellon Marlon A. McGill Martin Picard Victor I. Reus Christina M. Hough Jue Lin Elissa S. Epel Owen M. Wolkowitz Daniel Lindqvist
author_sort	Johan Fernström
title	Blood-based mitochondrial respiratory chain function in major depression
title_short	Blood-based mitochondrial respiratory chain function in major depression
title_full	Blood-based mitochondrial respiratory chain function in major depression
title_fullStr	Blood-based mitochondrial respiratory chain function in major depression
title_full_unstemmed	Blood-based mitochondrial respiratory chain function in major depression
title_sort	blood-based mitochondrial respiratory chain function in major depression
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/bb5e5046f7e5489088c9d6125ed82ea3
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Blood-based mitochondrial respiratory chain function in major depression

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