Antidepressants that increase mitochondrial energetics may elevate risk of treatment-emergent mania

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dc.coverageDOI: 10.1038/s41380-022-01888-x
dc.creatorGardea-Resendez, Manuel
dc.creatorCoombes, Brandon J.
dc.creatorVeldic, Marin
dc.creatorTye, Susannah J.
dc.creatorRomo-Nava, Francisco
dc.creatorOzerdem, Aysegul
dc.creatorPrieto, Miguel L.
dc.creatorCuellar-Barboza, Alfredo
dc.creatorNunez, Nicolas A.
dc.creatorSingh, Balwinder
dc.creatorPendegraft, Richard S.
dc.creatorMiola, Alessandro
dc.creatorMcElroy, Susan L.
dc.creatorBiernacka, Joanna M.
dc.creatorMorava, Eva
dc.creatorKozicz, Tamas
dc.creatorFrye, Mark A.
dc.date2022
dc.date.accessioned2025-11-18T19:42:17Z
dc.date.available2025-11-18T19:42:17Z
dc.description<p>Preclinical evidence suggests that antidepressants (ADs) may differentially influence mitochondrial energetics. This study was conducted to investigate the relationship between mitochondrial function and illness vulnerability in bipolar disorder (BD), specifically risk of treatment-emergent mania (TEM). Participants with BD already clinically phenotyped as TEM+ (n = 176) or TEM− (n = 516) were further classified whether the TEM associated AD, based on preclinical studies, increased (Mito+, n = 600) or decreased (Mito−, n = 289) mitochondrial electron transport chain (ETC) activity. Comparison of TEM+ rates between Mito+ and Mito− ADs was performed using generalized estimating equations to account for participants exposed to multiple ADs while adjusting for sex, age at time of enrollment into the biobank and BD type (BD-I/schizoaffective vs. BD-II). A total of 692 subjects (62.7% female, 91.4% White, mean age 43.0 ± 14.0 years) including 176 cases (25.3%) of TEM+ and 516 cases (74.7%) of TEM- with previous exposure to Mito+ and/or Mito- antidepressants were identified. Adjusting for age, sex and BD subtype, TEM+ was more frequent with antidepressants that increased (24.7%), versus decreased (13.5%) mitochondrial energetics (OR = 2.21; p = 0.000009). Our preliminary retrospective data suggests there may be merit in reconceptualizing AD classification, not solely based on monoaminergic conventional drug mechanism of action, but additionally based on mitochondrial energetics. Future prospective clinical studies on specific antidepressants and mitochondrial activity are encouraged. Recognizing pharmacogenomic investigation of drug response may extend or overlap to genomics of disease risk, future studies should investigate potential interactions between mitochondrial mechanisms of disease risk and drug response.</p>eng
dc.identifierhttps://investigadores.uandes.cl/en/publications/1a4b3418-eb77-4f26-8e7f-7fa164067ae5
dc.identifier.urihttps://repositorio.uandes.cl/handle/uandes/52262
dc.languageeng
dc.rightsinfo:eu-repo/semantics/openAccess
dc.sourcevol.28 (2022) nr.3 p.1020-1026
dc.subjectSDG 3 - Good Health and Well-being
dc.titleAntidepressants that increase mitochondrial energetics may elevate risk of treatment-emergent maniaeng
dc.typeArticleeng
dc.typeArtículospa
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