Orbitofrontal cortex volume prospectively predicts cannabis and other substance use onset in adolescents

Identifying neural characteristics that predict cannabis initiation is important for prevention efforts. The orbitofrontal cortex is critical for reward response and may be vulnerable to substance-induced alterations.

We measured orbitofrontal cortex thickness, surface area, and volume prior to the onset of use to predict cannabis involvement during an average nine-year follow-up.

Adolescents (n=118) aged 12-15 years completed baseline behavioral assessment and magnetic resonance imaging scans, then were followed up to 13 years with annual substance use interviews. Logistic regression examined baseline (pre-substance use) bilateral medial and lateral orbitofrontal cortex characteristics (volume, surface area, or cortex thickness) as predictors of regular cannabis use by follow-up. Post-hoc multinomial logistic regression assessed whether orbitofrontal cortex characteristics significantly predicted either alcohol use alone or cannabis+alcohol co-use. Brain-behavior relationships were assessed through follow-up correlations of baseline relationships between orbitofrontal cortex and executive functioning, reward responsiveness, and behavioral approach traits.

Larger left lateral orbitofrontal cortex volume predicted classification as cannabis user by follow-up (p=0.025, odds ratio=1.808). Lateral orbitofrontal cortex volume also predicted cannabis+alcohol co-user status (p=0.008, odds ratio=2.588), but not alcohol only status. Larger lateral orbitofrontal cortex volume positively correlated with greater baseline reward responsiveness (p=0.030, r=0.348). There were no significant results by surface area or cortex thickness (ps>0.05).

Larger left lateral orbitofrontal cortex measured from ages 12-15 years and prior to initiation of substance use was related to greater reward responsiveness at baseline and predicted classification as a cannabis user and cannabis+alcohol co-user by final follow-up. Larger lateral orbitofrontal cortex volume may represent aberrant orbitofrontal cortex maturation and increasing vulnerability for later substance use.