Substance Use in Young Men: Genes, Brain Function & Early Social Development

描述(由申请人提供)：本项目的目标是研究青年男子从青春期早期到成年期的物质使用模式中的生物学和早期发展因素。该项目建立在对310名高危青年男子的持续前瞻性纵向研究的基础上，这些青年男子从婴儿期起就使用多种方法(如观察法、访谈法)和告密者(如父母、教师、同龄人)，并跨越儿童、家庭和家庭外的危险因素进行跟踪。随着参与者进入成年期并面临人际关系和工具领域的挑战，该项目将整合遗传学和大脑功能的数据，以了解这些潜在的、新出现的生物因素的个体差异是如何单独和联合影响药物、酒精和尼古丁的使用模式的。大脑功能评估将通过对参与者纹状体对奖励刺激的反应性、杏仁核对威胁刺激的反应性、静息脑血流和静息功能连接性的功能磁共振成像，在两个时间点检查中脑边缘和皮质边缘神经回路的功能贡献。在这一点上，在纵向研究中纳入功能磁共振成像将提供关于大脑功能与遗传因素、早期发育、社会背景和物质使用之间的关联的详细信息。该项目的指导假设是，稳定的特征，如反社会行为和冲动的病史，家庭和家庭外的背景风险，大脑功能，以及与物质使用相关的大脑功能相关的基因变异，将有助于物质使用的纵向模式。此外，预计参与者在向成年过渡期间在建立稳定的浪漫关系和就业/教育培训方面取得的成功将减弱成年早期危险因素与药物使用模式之间的联系。该项目提供了一个史无前例的机会，可以检查从儿童早期到成年早期与药物使用有关的因素，并使用成人功能失调的高风险种族多样性男性的低收入样本，将这些数据与青春期到成年期过渡期间的基因和大脑功能数据联系起来。因此，这项研究提供了促进我们对物质使用问题的途径的理解的潜力，并指导发展知情的预防和干预努力。公共卫生相关性：该项目的目标是检查青年男子从青春期早期到成年期的物质使用模式中的生物学和早期发展因素。该项目建立在一项正在进行的前瞻性纵向研究的基础上，该研究对310名高危青年男性进行了前瞻性纵向研究，他们从婴儿期起就使用多种方法和告密者进行跟踪，涵盖儿童、家庭和家庭外的危险因素。这些数据将与青春期到成年期过渡过程中的基因和大脑功能数据联系起来。因此，这项研究提供了促进我们对物质使用问题的途径的理解的潜力，并指导发展知情的预防和干预努力。

DESCRIPTION (provided by applicant): The goal of this project is to examine biological and early developmental factors in patterns of substance use in young men from early adolescence to the transition to adulthood. The project builds on an ongoing prospective, longitudinal study of 310 high-risk young men who have been followed since infancy using multiple methods (e.g., observation, interview) and informants (e.g., parents, teachers, peers) and spanning child, family, and extra-familial risk factors. As participants undergo the transition to adulthood and face challenges in interpersonal and instrumental domains, the project will incorporate data on genetics and brain function to understand how these individual differences in underlying, emerging biology factors, separately and in combination, influence patterns of use for drugs, alcohol, and nicotine. Assessments of brain function will examine the contribution of function in mesolimbic and corticolimbic neural circuits at two time points by conducting functional MRI of participants' striatal reactivity to reward stimuli, amygdala reactivity to threat stimuli, resting cerebral blood flow, and resting functional connectivity. The inclusion of fMRI at this point in the longitudinal study will provide detailed information on the association between brain function and genetic factors, early development, social context, and substance use. The guiding hypothesis of the project is that stable characteristics such as a history of antisocial behavior and impulsivity; family and extra- familial contextual risk; brain function; and genetic variants associated with substance use- related brain function will contribute to longitudinal patterns of substance use. In addition, it is expected that the success participants have in establishing stable romantic relationships and employment/educational training during the transition to adulthood will attenuate associations between risk factors and patterns of substance use in early adulthood. The project provides an unprecedented opportunity to examine factors spanning from early childhood through early adulthood that are related to substance use and to link such data with data on genes and brain function during the transition from adolescence to adulthood using a low-income sample of ethnically diverse males at high risk for maladaptive adult functioning. Thus, the study offers the potential to advance our understanding of pathways to substance use problems and guide developmentally informed prevention and intervention efforts. PUBLIC HEALTH RELEVANCE: The goal of this project is to examine biological and early developmental factors in patterns of substance use in young men from early adolescence to the transition to adulthood. The project builds on an ongoing prospective, longitudinal study of 310 high-risk young men who have been followed since infancy using multiple methods and informants, and spanning child, family, and extra-familial risk factors. These data will be linked with data on genes and brain function during the transition from adolescence to adulthood. Thus, the study offers the potential to advance our understanding of pathways to substance use problems and guide developmentally informed prevention and intervention efforts.