Peripheral Blood Cytokines as Markers of Longitudinal Change in White Matter Microstructure Following Inpatient Treatment for Opioid Use Disorders

Background: Opioid use disorder (OUD) causes major public health morbidity and mortality. Although standard-of-care treatment with medications for OUD (MOUDs) is available, there are few biological markers of the clinical process of recovery. Neurobiological aspects of recovery can include normaliza...

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Main Authors: Eduardo R. Butelman, Yuefeng Huang, Sarah G. King, Pierre-Olivier Gaudreault, Ahmet O. Ceceli, Greg Kronberg, Flurin Cathomas, Panos Roussos, Scott J. Russo, Eric L. Garland, Rita Z. Goldstein, Nelly Alia-Klein
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Language:English
Published: Elsevier 2025-05-01
Series:Biological Psychiatry Global Open Science
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Online Access:http://www.sciencedirect.com/science/article/pii/S2667174325000345
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author Eduardo R. Butelman
Yuefeng Huang
Sarah G. King
Pierre-Olivier Gaudreault
Ahmet O. Ceceli
Greg Kronberg
Flurin Cathomas
Panos Roussos
Scott J. Russo
Eric L. Garland
Rita Z. Goldstein
Nelly Alia-Klein
author_facet Eduardo R. Butelman
Yuefeng Huang
Sarah G. King
Pierre-Olivier Gaudreault
Ahmet O. Ceceli
Greg Kronberg
Flurin Cathomas
Panos Roussos
Scott J. Russo
Eric L. Garland
Rita Z. Goldstein
Nelly Alia-Klein
author_sort Eduardo R. Butelman
collection DOAJ
description Background: Opioid use disorder (OUD) causes major public health morbidity and mortality. Although standard-of-care treatment with medications for OUD (MOUDs) is available, there are few biological markers of the clinical process of recovery. Neurobiological aspects of recovery can include normalization of brain white matter (WM) microstructure, which is sensitive to cytokine signaling. Here, we determined whether blood-based cytokines can be markers of change in WM microstructure following MOUD. Methods: Inpatient individuals with heroin use disorder (iHUDs) (n = 21) with methadone or buprenorphine MOUD underwent magnetic resonance imaging (MRI) scans with diffusion tensor imaging (DTI) and provided ratings of drug cue–induced craving, arousal, and valence earlier in treatment (MRI1) and ≈14 weeks thereafter (MRI2). Healthy control participants (HCs) (n = 24) also underwent 2 MRI scans during a similar time interval. At MRI2, participants provided a peripheral blood sample for multiplex quantification of serum cytokines. We analyzed the correlation of a multitarget biomarker score (from a principal component analysis of 19 cytokines that differed significantly between iHUDs and HCs) with treatment-related change in DTI metrics (ΔDTI; MRI2 − MRI1). Results: The cytokine biomarker score was negatively correlated with ΔDTI metrics in frontal, frontoparietal, and corticolimbic WM tracts in iHUDs but not in HCs. Also, serum levels of specific cytokines in the cytokine biomarker score, including the interleukin-related oncostatin M (OSM), similarly correlated with ΔDTI metrics in iHUDs but not in HCs. Serum levels of other specific cytokines were negatively correlated with changes in cue-induced craving and arousal in the iHUDs. Conclusions: Specific serum cytokines, studied alone or as a group, may serve as accessible biomarkers of WM microstructure changes and potential recovery in iHUDs undergoing treatment with MOUD.
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spelling doaj-art-17e88655367a4a819b7ecf91d81007b92025-08-20T03:05:23ZengElsevierBiological Psychiatry Global Open Science2667-17432025-05-015310048010.1016/j.bpsgos.2025.100480Peripheral Blood Cytokines as Markers of Longitudinal Change in White Matter Microstructure Following Inpatient Treatment for Opioid Use DisordersEduardo R. Butelman0Yuefeng Huang1Sarah G. King2Pierre-Olivier Gaudreault3Ahmet O. Ceceli4Greg Kronberg5Flurin Cathomas6Panos Roussos7Scott J. Russo8Eric L. Garland9Rita Z. Goldstein10Nelly Alia-Klein11Neuropsychoimaging of Addictions and Related Conditions Research Program, Icahn School of Medicine at Mount Sinai, Departments of Psychiatry and Neuroscience, New York, New York; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York; Eduardo R. Butelman, Ph.D.Neuropsychoimaging of Addictions and Related Conditions Research Program, Icahn School of Medicine at Mount Sinai, Departments of Psychiatry and Neuroscience, New York, New York; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New YorkNeuropsychoimaging of Addictions and Related Conditions Research Program, Icahn School of Medicine at Mount Sinai, Departments of Psychiatry and Neuroscience, New York, New York; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New YorkNeuropsychoimaging of Addictions and Related Conditions Research Program, Icahn School of Medicine at Mount Sinai, Departments of Psychiatry and Neuroscience, New York, New York; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New YorkNeuropsychoimaging of Addictions and Related Conditions Research Program, Icahn School of Medicine at Mount Sinai, Departments of Psychiatry and Neuroscience, New York, New York; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New YorkNeuropsychoimaging of Addictions and Related Conditions Research Program, Icahn School of Medicine at Mount Sinai, Departments of Psychiatry and Neuroscience, New York, New York; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New YorkFriedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New YorkDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York; Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, New York; Mental Illness Research, Education, and Clinical Center (VISN 2 South), James J. Peters Veterans Affairs, Medical Center, Bronx, New York; Center for Precision Medicine and Translational Therapeutics, James J. Peters Veterans Affairs, Medical Center, Bronx, New YorkFriedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York; Brain and Body Research Center, Icahn School of Medicine at Mount Sinai, New York, New York; Center of Affective Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New YorkDepartment of Psychiatry, University of California San Diego, La Jolla, California; Sanford Institute for Empathy and Compassion, University of California San Diego, La Jolla, CaliforniaNeuropsychoimaging of Addictions and Related Conditions Research Program, Icahn School of Medicine at Mount Sinai, Departments of Psychiatry and Neuroscience, New York, New York; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York; Center of Affective Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New YorkNeuropsychoimaging of Addictions and Related Conditions Research Program, Icahn School of Medicine at Mount Sinai, Departments of Psychiatry and Neuroscience, New York, New York; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York; Center of Affective Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York; Address correspondence to Nelly Alia-Klein, Ph.D.Background: Opioid use disorder (OUD) causes major public health morbidity and mortality. Although standard-of-care treatment with medications for OUD (MOUDs) is available, there are few biological markers of the clinical process of recovery. Neurobiological aspects of recovery can include normalization of brain white matter (WM) microstructure, which is sensitive to cytokine signaling. Here, we determined whether blood-based cytokines can be markers of change in WM microstructure following MOUD. Methods: Inpatient individuals with heroin use disorder (iHUDs) (n = 21) with methadone or buprenorphine MOUD underwent magnetic resonance imaging (MRI) scans with diffusion tensor imaging (DTI) and provided ratings of drug cue–induced craving, arousal, and valence earlier in treatment (MRI1) and ≈14 weeks thereafter (MRI2). Healthy control participants (HCs) (n = 24) also underwent 2 MRI scans during a similar time interval. At MRI2, participants provided a peripheral blood sample for multiplex quantification of serum cytokines. We analyzed the correlation of a multitarget biomarker score (from a principal component analysis of 19 cytokines that differed significantly between iHUDs and HCs) with treatment-related change in DTI metrics (ΔDTI; MRI2 − MRI1). Results: The cytokine biomarker score was negatively correlated with ΔDTI metrics in frontal, frontoparietal, and corticolimbic WM tracts in iHUDs but not in HCs. Also, serum levels of specific cytokines in the cytokine biomarker score, including the interleukin-related oncostatin M (OSM), similarly correlated with ΔDTI metrics in iHUDs but not in HCs. Serum levels of other specific cytokines were negatively correlated with changes in cue-induced craving and arousal in the iHUDs. Conclusions: Specific serum cytokines, studied alone or as a group, may serve as accessible biomarkers of WM microstructure changes and potential recovery in iHUDs undergoing treatment with MOUD.http://www.sciencedirect.com/science/article/pii/S2667174325000345Blood biomarkersCytokinesDiffusion tensor imagingHeroinOpioid use disorderRecovery
spellingShingle Eduardo R. Butelman
Yuefeng Huang
Sarah G. King
Pierre-Olivier Gaudreault
Ahmet O. Ceceli
Greg Kronberg
Flurin Cathomas
Panos Roussos
Scott J. Russo
Eric L. Garland
Rita Z. Goldstein
Nelly Alia-Klein
Peripheral Blood Cytokines as Markers of Longitudinal Change in White Matter Microstructure Following Inpatient Treatment for Opioid Use Disorders
Biological Psychiatry Global Open Science
Blood biomarkers
Cytokines
Diffusion tensor imaging
Heroin
Opioid use disorder
Recovery
title Peripheral Blood Cytokines as Markers of Longitudinal Change in White Matter Microstructure Following Inpatient Treatment for Opioid Use Disorders
title_full Peripheral Blood Cytokines as Markers of Longitudinal Change in White Matter Microstructure Following Inpatient Treatment for Opioid Use Disorders
title_fullStr Peripheral Blood Cytokines as Markers of Longitudinal Change in White Matter Microstructure Following Inpatient Treatment for Opioid Use Disorders
title_full_unstemmed Peripheral Blood Cytokines as Markers of Longitudinal Change in White Matter Microstructure Following Inpatient Treatment for Opioid Use Disorders
title_short Peripheral Blood Cytokines as Markers of Longitudinal Change in White Matter Microstructure Following Inpatient Treatment for Opioid Use Disorders
title_sort peripheral blood cytokines as markers of longitudinal change in white matter microstructure following inpatient treatment for opioid use disorders
topic Blood biomarkers
Cytokines
Diffusion tensor imaging
Heroin
Opioid use disorder
Recovery
url http://www.sciencedirect.com/science/article/pii/S2667174325000345
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