Frontal White Matter Changes Indicate Recovery With Inpatient Treatment In Heroin Addiction

ImportanceAmidst an unprecedented opioid epidemic, identifying neurobiological correlates of change with medication-assisted treatment of heroin use disorder is imperative. Distributed white matter (WM) impairments in individuals with heroin use disorder (iHUD) have been associated with increased drug craving, a reliable predictor of treatment outcomes. However, little is known about the extent of whole-brain structural connectivity changes with inpatient treatment and abstinence in iHUD. ObjectiveTo assess WM microstructure and associations with drug craving changes with inpatient treatment in iHUD (effects of time/re-scan compared to controls; CTL). DesignLongitudinal cohort study (12/2020-09/2022) where iHUD and CTL underwent baseline magnetic resonance imaging (MRI#1) and follow-up (MRI#2) scans, (mean interval of 13.9 weeks in all participants combined). SettingThe iHUD and CTL were recruited from urban inpatient treatment facilities and surrounding communities, respectively. ParticipantsThirty-four iHUD (42.1yo; 7 women), 25 age-/sex-matched CTL (40.5yo; 9 women). InterventionBetween scans, inpatient iHUD continued their medically-assisted treatment and related clinical interventions. CTL participants were scanned at similar time intervals. Main Outcomes and MeasuresChanges in white matter diffusion metrics [fractional anisotropy (FA), mean (MD), axial (AD), and radial diffusivities (RD)] in addition to baseline and cue-induced drug craving, and other clinical outcome variables (mood, sleep, affect, perceived stress, and therapy attendance). ResultsMain findings showed HUD-specific WM microstructure changes encompassing mostly frontal major callosal, projection, and association tracts, characterized by increased FA (.949<1- p<.986) and decreased MD (.949<1-p<.997) and RD (.949<1-p<.999). The increased FA (r=- 0.72, p<.00001) and decreased MD (r=0.69, p<.00001) and RD (r=0.67, p<.0001) in the genu and body of the corpus callosum and the left anterior corona radiata in iHUD were correlated with a reduction in baseline craving (.949<1-p<.999). No other WM correlations with outcome variables reached significance. Conclusions and RelevanceOur findings suggest whole-brain normalization of structural connectivity with inpatient medically-assisted treatment in iHUD encompassing recovery in frontal WM pathways implicated in emotional regulation and top-down executive control. The association with decreases in baseline craving further supports the relevance of these WM markers to a major symptom in drug addiction, with implications for monitoring clinical outcomes. Key pointsO_ST_ABSQuestionC_ST_ABSDoes white matter (WM) microstructure change with medication-assisted treatment in individuals with heroin use disorder (iHUD)? FindingsIn this longitudinal cohort study, diffusion MRI was acquired in 34 inpatient iHUD and 25 healthy controls (CTL) twice, separated by a mean of 13.9 weeks. We found HUD- specific WM microstructure changes with time, characterized by increased anisotropy and decreased diffusivity in fronto-striatal WM pathways. These changes were correlated with decreased baseline drug craving with treatment. MeaningFrontal WM changes and associated drug craving decreases suggest brain-behavior recovery with inpatient treatment in iHUD, potentially contributing to reduced drug use and sustained abstinence.