O'Brien Jessica W, Lichenstein Sarah D, Hill Shirley Y
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, Department of Psychology, University of Pittsburgh, Pittsburgh, Pennsylvania.
J Stud Alcohol Drugs. 2014 Jul;75(4):643-52. doi: 10.15288/jsad.2014.75.643.
Individuals with multiple alcohol-dependent (AD) relatives are at increased risk for substance use disorders (SUDs). Prospective, longitudinal studies of high-risk (HR) individuals afford the opportunity to determine potential risk markers of SUDs. The current study assessed the effect of familial risk and genetic variation on Iowa Gambling Task (IGT) performance and tested for an association between IGT performance and SUD outcomes.
Individuals from multiplex AD families (n = 63) and low-risk (LR; n = 45) control families, ages 16-34 years, were tested using a computerized version of the IGT. SUD outcomes were assessed at approximately yearly intervals. 5-HTTLPR and COMT genotypes were available for the majority of participants (n = 86).
HR offspring showed poorer performance overall on the IGT and especially poor performance on the final trial block (Block 5), indicating a failure to improve decision making with previous experience. The 5-HTTLPR short-allele homozygote participants performed worse than long-allele carriers, with HR S/S carriers exhibiting particularly poor performance. There was no main effect of COMT on IGT performance and no significant COMT by Risk interaction. Significantly more individuals in the HR than LR group met criteria for SUD. Importantly, disadvantageous performance on IGT Block 5 was significantly associated with an earlier age at SUD onset.
This is the first study to show that both familial risk of SUD and 5-HTTLPR variation impact performance on the IGT. Poorer IGT performance was associated with earlier onset of SUD, suggesting that HR individuals who fail to appropriately attend to long-term costs and benefits during a decision-making task are especially at risk for developing SUD in adolescence and young adulthood.
有多个酒精依赖（AD）亲属的个体患物质使用障碍（SUDs）的风险增加。对高危（HR）个体进行前瞻性纵向研究，为确定SUDs的潜在风险标志物提供了机会。本研究评估了家族风险和基因变异对爱荷华赌博任务（IGT）表现的影响，并测试了IGT表现与SUD结果之间的关联。
使用IGT的计算机化版本对来自多重AD家族（n = 63）和低风险（LR；n = 45）对照家族的16 - 34岁个体进行测试。大约每年评估一次SUD结果。大多数参与者（n = 86）可获得5 - HTTLPR和COMT基因型。
HR后代在IGT上总体表现较差，尤其是在最后一个试验块（第5块）表现很差，这表明未能通过以往经验改善决策。5 - HTTLPR短等位基因纯合子参与者的表现比长等位基因携带者差，HR S/S携带者表现尤其差。COMT对IGT表现没有主效应，且不存在风险与COMT的显著交互作用。HR组中符合SUD标准的个体明显多于LR组。重要的是，IGT第5块的不利表现与SUD发病年龄较早显著相关。
这是第一项表明SUD的家族风险和5 - HTTLPR变异均会影响IGT表现的研究。较差的IGT表现与SUD发病较早有关，这表明在决策任务中未能适当关注长期成本和收益的HR个体在青春期和青年期患SUD的风险尤其高。
