Association of Neural Responses to Drug Cues With Subsequent Relapse to Stimulant Use.
Level 3 - non-randomized controlled study
Prospective cohort study with healthy comparison group assessing fMRI cue reactivity as a predictor of clinical relapse
PubMed 30646331 · doi:10.1001/jamanetworkopen.2018.6466
What was done
Prospective cohort study comparing 36 veteran patients in a 28-day residential treatment program for stimulant use disorder with 40 healthy community controls. At baseline, participants underwent functional magnetic resonance imaging (fMRI) during a reward cue task measuring neural responses to drug and food cues in the medial prefrontal cortex (mPFC), nucleus accumbens (NAcc), and ventral tegmental area (VTA). Patients were prospectively followed at approximately 1, 3, and 6 months after discharge to assess stimulant relapse, measured as days to relapse and dichotomous relapse status at 3 months.
What was found
Compared with healthy controls, patients showed increased mesolimbic response to drug cues in the mPFC (t74 = 2.90, P = .005, Cohen d = 0.66), NAcc (t74 = 2.39, P = .02, Cohen d = 0.54), and VTA (t74 = 4.04, P < .001, Cohen d = 0.92). In patients, elevated NAcc response to drug cues was associated with time to relapse (Cox proportional hazards HR, 2.30; 95% CI, 1.40-3.79), whereas mPFC and VTA responses were not. After controlling for age, NAcc activation classified 3-month relapsers (n = 12) versus abstainers (n = 21) with 75.8% accuracy, outperforming conventional clinical and demographic predictors.
Why it matters
This study identifies nucleus accumbens cue reactivity as a potential objective neural biomarker for stimulant relapse vulnerability. If replicated, neural measures could help stratify risk and target intensive relapse-prevention interventions.
Limits
The patient cohort was small (n = 36) and predominantly male veterans (34 men, 2 women), limiting generalizability. There were notable age differences between controls (mean 32.0 years) and patients (mean 43.4 years), as well as between relapsers (49.3 years) and abstainers (39.3 years). Only 33 of 36 patients were included in the 3-month classification analysis.
Cited by
- supports In a residential treatment study of individuals with methamphetamine addiction, cue-elicited fMRI activation in the nucleus accumbens predicted relapse, whereas participants' self-reported craving or feelings toward drug cues did not.