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 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) ( = 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) ( = 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.