Developmental pathways into adolescent substance abuse: neurophysiologic, genetic and environmental determinants

在这项研究中，我们希望更好地了解基因、大脑功能和环境影响之间的相互作用，以及它们是如何导致青少年滥用酒精、尼古丁和大麻的。为此，我们将检查IMAGEN样本中2000名14岁的参与者，他们的特征是使用功能性神经成像分析行为过程，如奖励依赖、冲动和情绪反应，这些行为过程被认为与青少年药物滥用的发展有关。此外，除了广泛的行为和临床评估外，还对这些儿童进行了全基因组分析。我们现在建议扩展IMAGEN研究，以便观察在酒精、尼古丁或药物暴露以及社会心理压力等缓和环境因素的背景下物质使用模式的发展。我们的目标是确定和描述基因、脑功能和环境影响的多维风险概况，这有助于我们预测早期药物滥用的风险，包括酗酒、吸烟或滥用大麻。我们将在10000名青少年的第二大队列ALSPAC队列中测试我们的模型。我们的最终目标是促进在风险概况携带者中制定具体的早期干预措施，以减少青少年药物滥用的发生率。

In this study we want to learn to better understand the interplay of genes, brain function and environmental influences and how they result in the development of adolescent abuse of alcohol, nicotine and cannabis. To this end we will examine 2000 14 year old participants of the IMAGEN sample which have been characterised using functional neuroimaging analysis of behavioural processes like reward dependence, impulsivity and emotional reactivity which are known to be relevant for the development of adolescent substance abuse. In addition, to extensive behavioural and clinical assessments, a genome-wide analysis has been carried out in these children. We now propose to extend the IMAGEN study in order to observe the development of substance use patterns in the context of moderating environmental factors, such as exposure to alcohol, nicotine or drugs as well as psychosocial stress. We aim to identify and to characterise a multidimensional risk profile of genes, brain function and environmental influences which helps us to predict risk for early onset substance abuse, including binge drinking, smoking or cannabis abuse. We will test our model in a second large cohort of 10000 adolescents, the ALSPAC cohort. Our final goal is to contribute to the development of specific early interventions in carriers of the risk profile to reduce the incidence of adolescent substance abuse.