Neurocognitive and psychiatric markers for addiction: Common vs. specific (endo)phenotypes for opiate and stimulant dependence

Abstract

BACKGROUND. The differential utility of neurocognitive impulsivity and externalizing/internalizing traits as putative addiction endophenotypes among individuals dependent on opiates vs. stimulants is unclear. The present study aims to determine: (1) whether neurocognitive impulsivity dimensions and externalizing/internalizing traits are correlated between siblings discordant for opiate and stimulant dependence; and (2) which of these associations are common across substances and which are substancespecific. METHOD. Pearson correlations between individuals with 'pure' heroin and 'pure' 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 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. CONCLUSIONS. 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 and trait impulsivity 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 substancespecific dependencies.

Impulsivities and addictions: a multidimensional integrative framework informing assessment and interventions for substance use disorders

“…ADHD [145] and anxiety sensitivity [146] were specific to sibling-pairs discordant for amphetamine dependence, whereas hopelessness (measured with the Substance Use Risk Profile Scale [32]) was specific to sibling-pairs discordant for heroin dependence [144], suggesting that these traits are specifically implicated as endophenotypes, and not consequences, of drug use. Finally, neurocognitive indices of impulsive choice were common to both opiate and stimulant sibpairs (general risk), whereas an index of impulsive action, go/no-go commission errors, was specific to amphetamine sibling-pairs (substance-specific risk linked to ADHD) [144]. These substance-specific phenotypic associations suggest that certain endophenotypic markers may be common across addictions, whereas others may be specific to risk for dependence on specific classes of drugs.…”

“…For example, trait impulsiveness (measured with the Barratt Impulsiveness Scale-11 [26]) appears to be a putative endophenotype for stimulant dependence, as indicated by significant correlations between sibling-pairs of stimulant-dependent individuals and their biological non-dependent siblings [43,144]. In contrast, sensation seeking (measured with the Sensation Seeking Scale-Form V [24]) was specific for sibling-pairs discordant for heroin dependence [144]. ADHD [145] and anxiety sensitivity [146] were specific to sibling-pairs discordant for amphetamine dependence, whereas hopelessness (measured with the Substance Use Risk Profile Scale [32]) was specific to sibling-pairs discordant for heroin dependence [144], suggesting that these traits are specifically implicated as endophenotypes, and not consequences, of drug use.…”

“…In contrast, sensation seeking (measured with the Sensation Seeking Scale-Form V [24]) was specific for sibling-pairs discordant for heroin dependence [144]. ADHD [145] and anxiety sensitivity [146] were specific to sibling-pairs discordant for amphetamine dependence, whereas hopelessness (measured with the Substance Use Risk Profile Scale [32]) was specific to sibling-pairs discordant for heroin dependence [144], suggesting that these traits are specifically implicated as endophenotypes, and not consequences, of drug use. Finally, neurocognitive indices of impulsive choice were common to both opiate and stimulant sibpairs (general risk), whereas an index of impulsive action, go/no-go commission errors, was specific to amphetamine sibling-pairs (substance-specific risk linked to ADHD) [144].…”

“…These findings are consistent with twin and sibling-pairs design studies reporting evidence for potential substance-specificity of different trait and state markers. For example, trait impulsiveness (measured with the Barratt Impulsiveness Scale-11 [26]) appears to be a putative endophenotype for stimulant dependence, as indicated by significant correlations between sibling-pairs of stimulant-dependent individuals and their biological non-dependent siblings [43,144]. In contrast, sensation seeking (measured with the Sensation Seeking Scale-Form V [24]) was specific for sibling-pairs discordant for heroin dependence [144].…”