Neurocognitive and Psychiatric Markers for Addiction: Common vs. Specific Endophenotypes for Heroin and Amphetamine Dependence

Background: The differential utility of neurocognitive impulsivity and externalizing/ internalizing traits as putative endophenotypes for dependence on heroin vs. amphetamine is unclear.

Objective: This exploratory study aims to determine: (1) whether neurocognitive impulsivity dimensions and externalizing/internalizing traits are correlated between siblings discordant for heroin and amphetamine dependence; and (2) which of these associations are common across substances and which are substance- specific.

Methods: Pearson correlations between individuals with 'pure' heroin and amphetamine dependence and their unaffected biological siblings (n = 37 heroin sibling pairs; n = 30 amphetamine sibling pairs) were run on 10 neurocognitive measures, 6 externalizing measures, and 5 internalizing measures. Sibling pair effects were further examined using regression.

Results: Siblings discordant for heroin dependence were significantly correlated on delay aversion on the Cambridge Gambling Task, risk-taking on the Balloon Analogue Risk Task, sensation seeking, and hopelessness. Siblings discordant for amphetamine dependence were significantly correlated on the quality of decision-making on the Cambridge Gambling Task, discriminability on the Immediate Memory Task, commission errors on the Go/No Go Task, trait impulsivity, ADHD and anxiety sensitivity.

Conclusion: Dimensions of impulsivity and externalizing/internalizing traits appear to aggregate among siblings discordant for substance dependence. Risk-taking propensity, sensation seeking and hopelessness were specific for heroin sibling pairs. Motor/action impulsivity, trait impulsivity, and anxiety sensitivity were specific to amphetamine sibling pairs. Decisional/choice impulsivity was common across both heroin and amphetamine sibling pairs. These findings provide preliminary evidence for the utility of neurocognitive impulsivity and externalizing/ internalizing traits as candidate endophenotypes for substance dependence in general and for substance-specific dependencies.