Shared and substance specific white matter alterations across opioid, cannabis, and nicotine dependence and their association with impulsive decision making

Kurzzusammenfassung in leicht verständlicher Sprache

People with addictions to cannabis, opioids, or nicotine often exhibit changes in brain connections. In this study, participants with these addictions and healthy individuals were examined using a specialized MRI technique. Cannabis addiction revealed more pronounced changes in a fiber tract, the middle longitudinal fasciculus, which is associated with rash, impulsive decision-making. These findings help to understand how the severity of substance use is related to changes in the brain and decision-making behavior.

Abstract

Hintergrund und Fragestellung
Substance use disorders (SUDs) are associated with white matter (WM) microstructural abnormalities, but direct comparisons across different substances and their relationship to impulsive choice remain limited. Diffusion MRI, including diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI), provides complementary sensitivity to WM alterations. We examined whether opioid, cannabis, and nicotine dependence show shared and substance specific WM changes, and whether alterations in the middle longitudinal fasciculus (MLF) relate to delay discounting (DD).

Methoden
In this cross-sectional dual center diffusion MRI study, 87 individuals with SUDs, 48 ??with cannabis dependence (CUD), 16 with opioid dependence (OUD), and 23 with nicotine dependence (NUD), and 53 nonsmoking healthy controls were examined. Whole brain tract based spatial statistics and tract specific analyzes of the MLF were performed on DTI and NODDI metrics. DD was assessed with the Kirby Delay Discounting Task. Exploratory mediation models examined whether substance use severity influenced associations between MLF microstructure and impulsive choice.

Ergebnisse
OUD and CUD showed convergent widespread WM abnormalities, with reduced fractional anisotropy and increased mean diffusivity and orientation dispersion across fronto-temporo-parietal and limbic pathways, including the superior longitudinal fasciculus, arcuate fasciculus, cingulum, and MLF. NUD showed circumscribed alterations in the anterior corona radiata and genu of the corpus callosum. In CUD, higher MLF orientation dispersion was associated with steeper DD, and exploratory moderated mediation analyzes indicated that this association is related to cannabis consumption, with the strongest associations in daily users. No significant MLF-DD associations were observed in OUD.

Diskussion und Schlussfolgerung
The findings indicate both shared and substance specific WM disruption across OUD, CUD, and NUD. In CUD, greater MLF orientation dispersion was associated with more impulsive choice, indirectly driven by cannabis use severity, suggesting a neurobiological pathway linking temporo-parietal WM organization to DD in CUD.

Interessenskonflikte sowie Erklärung zur Finanzierung
Conflicts of interest and disclosure for the promotion
I, or rather the co-authors, declare that during the last 3 years there have been no economic advantages or personal connections that could have influenced the work on the submitted abstract.
The study was funded by the Federal Ministry of Education and Research (BMBF, grant numbers 01ZX1909C and 01ZX2209C, SysMedSUDs to GE, WHS, HW), the German Research Foundation (DFG, grant number 402170461, TRR 265 to PB, WHS, HW) and the ERA-Net JTC program (grant number 01EW2402-IBRAA to WHS).