Frontal White Matter Changes and Craving Recovery in Inpatients With Heroin Use Disorder.

Importance: Amidst an unprecedented opioid epidemic, identifying neurobiological correlates of change with medication-assisted treatment of heroin use disorder is imperative. White matter impairments in individuals with heroin use disorder (HUD) have been associated with drug craving, a reliable predictor of treatment outcomes; however, little is known about structural connectivity changes with inpatient treatment and abstinence in individuals with HUD. Objective: To assess white matter microstructure and associations with drug craving changes with inpatient treatment in individuals with HUD (effects of time and rescan compared with controls). Design, Setting, and Participants: This cohort study conducted from December 2020 to September 2022 included individuals recruited from urban inpatient treatment facilities treating HUD and surrounding communities in New York City. Participants with HUD were receiving medication-assisted treatment. Data were analyzed from October 2022 to March 2023. Intervention: Between scans, inpatient individuals with HUD continued treatment and related clinical interventions. Control participants were scanned at similar time intervals. Main Outcomes and Measures: Changes in white matter diffusion metrics (fractional anisotropy and mean, axial, and radial diffusivities) assessed voxelwise with general linear models in addition to baseline and cue-induced drug craving, and other clinical outcome variables (mood, sleep, affect, perceived stress, and therapy attendance). Results: Thirty-four individuals with HUD (mean [SD] age, 40.5 [11.0] years; 9 women [36%]; 3 Black [9%], 17 White [50%], 14 other race or ethnicity [41%]) and 25 control (mean [SD] age, 42.1 [9.0]; 7 women [21%]; 8 Black [32%], 10 White [40%], 7 other race or ethnicity [28%]) were included. Main voxelwise findings showed HUD-specific white matter microstructure changes (1 - P > .949), including increased fractional anisotropy and decreased mean and radial diffusivities, encompassing mostly frontal major callosal, projection, and association tracts. The increased fractional anisotropy (r = -0.72, P < .001, slope SE = 9.0 × 10-4) and decreased mean diffusivity (r = 0.69, P < .001, slope SE = 1.25 × 10-6) and/or radial diffusivity (r = 0.67, P < .001, slope SE = 1.16 × 10-6) in the genu and body of the corpus callosum and left anterior corona radiata in individuals with HUD correlated with a reduction in baseline craving (voxelwise 1 - P > .949). No other white matter correlations with outcome variables reached significance. Conclusions and Relevance: This cohort study of inpatients with HUD on medication-assisted treatment found whole-brain normalization of structural connectivity in frontal white matter pathways implicated in emotional regulation and top-down executive control. Observed associations with decreases in baseline craving further support the possibility of recovery, highlighting the relevance of these white matter markers to a major symptom of addiction, with implications for clinical outcome monitoring.