Peripheral Blood Cytokines as Markers of Longitudinal Change in White Matter Microstructure Following Inpatient Treatment for Opioid Use Disorders
Biological Psychiatry Global Open Science, 2025
Butelman E., Huang Y., King S., Gaudreault P., Ceceli A., Kronberg G., Cathomas F., Roussos P., Russo S., Garland E., Goldstein R., Alia-Klein N.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Neurology | Patient Stratification | Serum |  Olink Target 96 |
Abstract
Background
Opioid use disorder (OUD) causes major public health morbidity and mortality. Although standard-of-care treatment with medications for OUD (MOUD) 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 determine whether blood-based cytokines can be markers of change in WM microstructure following MOUD.
Methods
Inpatient individuals with heroin use disorder (iHUD; n=21) with methadone or buprenorphine MOUD underwent magnetic resonance 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 controls (HC; n=24) also underwent two MRI scans at a similar time interval. At MRI2, participants provided a peripheral blood sample for multiplex quantification of serum cytokines. We analyzed the correlation of a multi-target biomarker score (from a principal component analysis of 19 cytokines that differed between iHUD and HC) with treatment-related change in DTI metrics (ΔDTI; MRI2 – MRI1).
Results
The cytokine biomarker score was negatively correlated with ΔDTI metrics in frontal, fronto-parietal, and cortico-limbic WM tracts in iHUD, but not HC. Also, serum levels of specific cytokines in the cytokine biomarker score, including the interleukin-related oncostatin M (OSM) similarly correlated with ΔDTI metrics in iHUD, but not in HC. Serum levels of other specific cytokines were negatively correlated with changes in cue-induced craving and arousal in the iHUD.
Conclusions
Specific serum cytokines, studied alone or as a group, serve as accessible biomarkers of WM microstructure changes and potential recovery in iHUD undergoing treatment with MOUD.