FRONTAL WHITE MATTER CHANGES INDICATE RECOVERY WITH INPATIENT TREATMENT IN HEROIN ADDICTION
Authors: Gaudreault Pierre-Olivier , King Sarah G , Huang Yuefeng , Ceceli Ahmet O. , Kronberg Greg , Alia-Klein Nelly , Goldstein Rita Z. 
Published: June 2024

Importance

Amidst 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.

Objective

To assess WM microstructure and associations with drug craving changes with inpatient treatment in iHUD (effects of time/re-scan compared to controls; CTL).

Design

Longitudinal 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).

Setting

The iHUD and CTL were recruited from urban inpatient treatment facilities and surrounding communities, respectively.

Participants

Thirty-four iHUD (42.1yo; 7 women), 25 age-/sex-matched CTL (40.5yo; 9 women).

Intervention

Between scans, inpatient iHUD continued their medically-assisted treatment and related clinical interventions. CTL participants were scanned at similar time intervals.

Main Outcomes and Measures

Changes 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).

Results

Main 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 Relevance

Our 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 points

Question

Does white matter (WM) microstructure change with medication-assisted treatment in individuals with heroin use disorder (iHUD)?

Findings

In 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.

Meaning

Frontal 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.