Multidimensional predictors of antidepressant responses: Integrating mitochondrial, genetic, metabolic and environmental factors with clinical outcomes

Major depressive disorder (MDD) is a primary psychiatric illness worldwide; there is a dearth of new mechanistic models for the development of better therapeutic strategies. Although we continue to discover individual biological factors, a major challenge is the identification of integrated, multidi...

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Autores principales:	Carla Nasca, Olivia Barnhill, Paolo DeAngelis, Kathleen Watson, Jue Lin, James Beasley, Sarah P. Young, Alison Myoraku, Josh Dobbin, Benedetta Bigio, Bruce McEwen, Natalie Rasgon
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Acetylcarnitine Metabolism Stress Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Neurophysiology and neuropsychology QP351-495
Acceso en línea:	https://doaj.org/article/5764d2df443a4d5b98069881a9dc8928
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spelling	oai:doaj.org-article:5764d2df443a4d5b98069881a9dc89282021-11-12T04:37:27ZMultidimensional predictors of antidepressant responses: Integrating mitochondrial, genetic, metabolic and environmental factors with clinical outcomes2352-289510.1016/j.ynstr.2021.100407https://doaj.org/article/5764d2df443a4d5b98069881a9dc89282021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2352289521001156https://doaj.org/toc/2352-2895Major depressive disorder (MDD) is a primary psychiatric illness worldwide; there is a dearth of new mechanistic models for the development of better therapeutic strategies. Although we continue to discover individual biological factors, a major challenge is the identification of integrated, multidimensional traits underlying the complex heterogeneity of depression and treatment outcomes. Here, we set out to ascertain the emergence of the novel mitochondrial mediator of epigenetic function acetyl-L-carnitine (LAC) in relation to previously described individual predictors of antidepressant responses to the insulin-sensitizing agent pioglitazone. Herein, we report that i) subjects with MDD and shorter leukocyte telomere length (LTL) show decreased levels of LAC, increased BMI, and a history of specific types of childhood trauma; and that ii) these multidimensional factors spanning mitochondrial metabolism, cellular aging, metabolic function, and childhood trauma provide more detailed signatures to predict longitudinal changes in depression severity in response to pioglitazone than individual factors. The findings of multidimensional signatures involved in the pathophysiology of depression and their role in predicting treatment outcomes provide a starting point for the development of a mechanistic framework linking biological networks and environmental factors to clinical outcomes in pursuit of personalized medicine strategies to effectively treat MDD.Carla NascaOlivia BarnhillPaolo DeAngelisKathleen WatsonJue LinJames BeasleySarah P. YoungAlison MyorakuJosh DobbinBenedetta BigioBruce McEwenNatalie RasgonElsevierarticleAcetylcarnitineMetabolismStressNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429Neurophysiology and neuropsychologyQP351-495ENNeurobiology of Stress, Vol 15, Iss , Pp 100407- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Acetylcarnitine Metabolism Stress Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Neurophysiology and neuropsychology QP351-495
spellingShingle	Acetylcarnitine Metabolism Stress Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Neurophysiology and neuropsychology QP351-495 Carla Nasca Olivia Barnhill Paolo DeAngelis Kathleen Watson Jue Lin James Beasley Sarah P. Young Alison Myoraku Josh Dobbin Benedetta Bigio Bruce McEwen Natalie Rasgon Multidimensional predictors of antidepressant responses: Integrating mitochondrial, genetic, metabolic and environmental factors with clinical outcomes
description	Major depressive disorder (MDD) is a primary psychiatric illness worldwide; there is a dearth of new mechanistic models for the development of better therapeutic strategies. Although we continue to discover individual biological factors, a major challenge is the identification of integrated, multidimensional traits underlying the complex heterogeneity of depression and treatment outcomes. Here, we set out to ascertain the emergence of the novel mitochondrial mediator of epigenetic function acetyl-L-carnitine (LAC) in relation to previously described individual predictors of antidepressant responses to the insulin-sensitizing agent pioglitazone. Herein, we report that i) subjects with MDD and shorter leukocyte telomere length (LTL) show decreased levels of LAC, increased BMI, and a history of specific types of childhood trauma; and that ii) these multidimensional factors spanning mitochondrial metabolism, cellular aging, metabolic function, and childhood trauma provide more detailed signatures to predict longitudinal changes in depression severity in response to pioglitazone than individual factors. The findings of multidimensional signatures involved in the pathophysiology of depression and their role in predicting treatment outcomes provide a starting point for the development of a mechanistic framework linking biological networks and environmental factors to clinical outcomes in pursuit of personalized medicine strategies to effectively treat MDD.
format	article
author	Carla Nasca Olivia Barnhill Paolo DeAngelis Kathleen Watson Jue Lin James Beasley Sarah P. Young Alison Myoraku Josh Dobbin Benedetta Bigio Bruce McEwen Natalie Rasgon
author_facet	Carla Nasca Olivia Barnhill Paolo DeAngelis Kathleen Watson Jue Lin James Beasley Sarah P. Young Alison Myoraku Josh Dobbin Benedetta Bigio Bruce McEwen Natalie Rasgon
author_sort	Carla Nasca
title	Multidimensional predictors of antidepressant responses: Integrating mitochondrial, genetic, metabolic and environmental factors with clinical outcomes
title_short	Multidimensional predictors of antidepressant responses: Integrating mitochondrial, genetic, metabolic and environmental factors with clinical outcomes
title_full	Multidimensional predictors of antidepressant responses: Integrating mitochondrial, genetic, metabolic and environmental factors with clinical outcomes
title_fullStr	Multidimensional predictors of antidepressant responses: Integrating mitochondrial, genetic, metabolic and environmental factors with clinical outcomes
title_full_unstemmed	Multidimensional predictors of antidepressant responses: Integrating mitochondrial, genetic, metabolic and environmental factors with clinical outcomes
title_sort	multidimensional predictors of antidepressant responses: integrating mitochondrial, genetic, metabolic and environmental factors with clinical outcomes
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/5764d2df443a4d5b98069881a9dc8928
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Multidimensional predictors of antidepressant responses: Integrating mitochondrial, genetic, metabolic and environmental factors with clinical outcomes

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