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的相互作用，以及它们如何导致青少年滥用酒精、尼古丁和大麻。为此，我们将检查IMAGEN样本中2000名14岁的参与者，这些参与者已使用奖励依赖、冲动和情绪反应等行为过程的功能神经成像分析进行特征分析，这些行为过程已知与青少年药物滥用的发展相关。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，以观察在缓和环境因素（如暴露于酒精、尼古丁或药物以及心理社会压力）的背景下物质使用模式的发展。我们的目标是识别和分析基因、脑功能和环境影响的多维风险特征，这有助于我们预测早发性药物滥用的风险，包括酗酒、吸烟或大麻滥用。我们将在第二个包含10000名青少年的大型队列ALSPAC队列中测试我们的模型。我们的最终目标是促进制定针对风险状况携带者的具体早期干预措施，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.