Substance use involvement moderates the effect of cortisol response on white-matter microstructure longitudinally

Introduction Stress contributes to substance use (SU) involvement (SUI) and differences in brain white matter (WM). However, longitudinal relationships involving SUI, stress hormones, and WM are not well understood. This study examined the moderating role of SUI on the prospective association between cortisol response (CR) and WM microstructure.Methods Data were drawn from a larger longitudinal study on SU disorder (SUD) aetiology. Participants were enrolled at ages 10–12 years when salivary cortisol was assayed. The Drug Use Chart assessed cumulative involvement with 10 substance categories by age 18 years. Diffusion-weighted data were acquired from sixty-nine participants after reaching age 18 years and were used to compute crossing-fibre measures. Analyses were conducted in a priori regions of interest linked to SU and stress.Results CR levels were related to secondary- and tertiary-fibre anisotropy in the cingulum. SUI moderated associations between CR and right cingulum secondary-fibre anisotropy wherein CR levels associated with greater anisotropy at heightened SUI levels.Conclusions This study identified stress-linked differences in distinct cingulum WM fibres among individuals with greater SUI. Involvement with SU overall, may modulate stress effects and enhance WM anisotropy in region- and fibre-specific manners. Potential biomarkers associated with SUI in WM among vulnerable stress-exposed youth require further investigation with respect to SUD aetiology.