Pre‐ejection period reactivity and psychiatric comorbidity prospectively predict substance use initiation among middle‐schoolers: A pilot study

Youth with conduct problems (CPs) or depression are at high risk for early initiation of substance use, and for future substance use disorders (SUDs). Comorbid CPs and depression increase risk even further, yet understanding how these conditions interact remains elusive. One hypothesis is that altered mesolimbic dopamine function contributes to symptoms of CPs, depression, and SUDs. Cardiac pre-ejection period (PEP) reactivity to incentives is linked theoretically and functionally to central dopamine responding. We evaluated PEP reactivity to reward as a prospective biomarker of substance use in a study of 206 youth with depression, CPs, CPs and depression, or no psychiatric condition. Children were 8-12 years old at the first of three annual assessments. Reduced PEP reactivity was associated with increased likelihood of future alcohol use, and CPs interacted with anxiety and depression to double risk for marijuana and other substance use.