Distinct drug and aversive cue-reactivity patterns are associated with opioid use disorder.

Background

Although addiction models posit that drug and aversive cues contribute to relapse, few studies have investigated cue-elicited biomarkers of relapse in opioid use disorder (OUD).

Methods

Individuals with OUD (n=64, 20F) and healthy controls (CTL; n=35, 19F) completed a cue-reactivity task during functional magnetic resonance imaging at baseline. Participants viewed Negative, Neutral, and Drug cues and provided ratings of valence, arousal, stress, and urge to use drugs. OUD participants were followed up for a three-month period to determine abstinence (n=29) versus relapse (n=35). Blood oxygen-level-dependent (BOLD) signals were extracted from striatum, insula, anterior cingulate cortex [ACC], amygdala, and hippocampus regions of interest (ROI). Linear mixed effects models were computed for ratings and ROI BOLD signals with group (OUD versus CTL; Abstinent versus Relapsed OUD subgroups) and condition as fixed factors. Whole-brain analyses were computed to complement ROI analyses, and both were corrected for multiple comparisons.

Results

Compared to CTL, OUD reported greater arousal, stress, and urge ratings to Drug cues but exhibited lower nucleus accumbens, insula, and ACC ROI BOLD signal to Negative cues. Whole-brain results replicated this pattern in OUD and also revealed blunted (a) inferior frontal and precentral gyri responses to Negative cues; and (b) orbitofrontal cortex responses to Drug cues. In contrast, OUD subgroups did not differ on subjective or brain responses.

Conclusions

Disengagement from aversive stimuli via interoceptive and reward circuitry may be a vulnerability marker for OUD. Replication is warranted across additional aversive paradigms and OUD samples powered to evaluate longitudinal outcomes.