Effects of heavy adolescent cannabis use on brain morphology in aging

说明(由申请人提供)：大麻(大麻)是全世界使用最广泛的非法药物，2010年有1 740万美国人报告过去一个月使用大麻，460万人符合依赖标准，强调了了解使用的生物影响对公共卫生的重要性。大量使用大麻如何影响晚年的大脑结构和认知能力尚不清楚。青春期大脑的不断成熟，包括记忆表现和执行控制的发育回路，使青春期大脑面临大量使用大麻的有害影响的高风险。随着婴儿潮一代的老龄化，许多青少年时期大量吸食大麻的人现在正进入晚年，届时与年龄相关的认知能力可能会开始下降。在20世纪70年代的S时代，大麻的使用量在不到十年的时间里翻了一番，当时在美国药物滥用调查中，38%的受访者报告使用大麻，12%的吸毒者报告每月吸食大麻超过20次。了解早期大量使用大麻可能会如何影响神经生物学和认知结果，对于这一老龄化人口来说非常重要，因为他们已经面临着衰老中记忆和认知缺陷的风险。由于大麻的使用似乎在海马体内产生主要影响，海马体是记忆的主要结构，也是受年龄相关记忆障碍和临床前阿尔茨海默病影响最大的结构，我们预计长期使用大麻的影响可能在衰老过程中最大。据我们所知，在老龄化人口中，还没有研究调查青少年使用大麻对海马体形态和认知表现的长期影响。我们将使用高分辨率磁共振成像(MRI)、扩散张量成像(DTI)和神经心理测试来研究青春期期间每月吸食大麻超过20次至少一年的老年人群(55-70岁)的海马体完整性和认知表现。在我们建议纳入这一高使用量类别的30名受试者中，我们已经确定了9名受试者，并收集了这些受试者的磁共振成像、DTI和认知测试数据。我们将把从大量吸食大麻的人收集的数据与没有吸食大麻但在年龄、性别、教育程度、少量烟草和少量酒精使用方面匹配的受试者进行比较。最后，由于家族史和遗传风险已知会加速老化过程中海马体的形态和记忆衰退，我们将调查重度吸食大麻者是否拥有APOE？4变异体与较薄的海马皮层和白质缺陷之间存在协同关系。该项目通过在她之前对老化大脑的神经成像研究的优势基础上，同时在成瘾研究方面提供新的培训和指导，来推进应聘者的培训。该培训计划结合了正式的课程作业、与Edythe London博士的一对一指导，以及一系列会议和研讨会，以促进候选人在成瘾研究方面的成长。Edythe London博士是一名成瘾研究方面的知名研究员。

DESCRIPTION (provided by applicant): Marijuana (Cannabis sativa) is the most widely used illicit drug worldwide, with 17.4 million Americans reporting past month use in 2010 and 4.6 million meeting criteria for dependence, underscoring the public health importance of understanding the biological implications of use. How heavy cannabis use affects brain structure and cognitive performance in late life is unknown. The ongoing maturation in the adolescent brain, including the developmental circuitry underlying memory performance and executive control puts the adolescent brain at high risk for detrimental effects of heavy cannabis use. With the aging of the 'baby boomer' generation, many people who used cannabis heavily as adolescents are now entering their senior years when age-related cognitive decline may begin. Cannabis use doubled in less than a decade during the 1970's when 38% of those surveyed in the U.S. Survey on Drug Abuse reported using cannabis and 12% of those users reported using cannabis more than 20 times a month. Understanding how heavy, early cannabis use may affect neurobiological and cognitive outcomes is of high importance for this aging population, which is already at risk for memory and cognitive deficits in aging. Because cannabis use appears to have a primary effect within the hippocampus, the main structure for memory and the structure affected most by age-related memory impairments and pre-clinical Alzheimer's disease, we expect that the effects of chronic cannabis use may be greatest during aging. To our knowledge, no study has investigated the long-term effects of adolescent cannabis use on hippocampal morphology and cognitive performance in an aging population. We will investigate hippocampal integrity and cognitive performance using high-resolution magnetic resonance imaging (MRI), diffusion tensor imaging (DTI) and neuropsychological testing in an aging population of subjects (55-70 years old) who used cannabis more than 20 times a month for at least a year during adolescence. Of the 30 subjects we propose to enroll in this heavy use category, we have already identified 9 subjects, and collected MRI, DTI and cognitive testing data for these subjects. We will compare data collected from heavy cannabis users to subjects who did not use cannabis but are matched for age, gender, education, light tobacco and light alcohol use. Finally, because family history and genetic risk are known to accelerate hippocampal morphology and memory decline in aging, we will investigate whether possession of the APOE ¿4 variant in heavy cannabis users is synergistically related to thinner hippocampal cortex and white matter deficits. This project advances the Candidate's training by building on the strengths of her previous research in neuroimaging of the aging brain while providing new training and mentorship in addiction research. The training program combines formal coursework, one-on-one mentoring with Dr. Edythe London, an established investigator in addiction research, and a series of meeting and workshops to foster the Candidate's growth in addiction research.