METHAMPHETAMINE CHILDREN

冰毒儿童

• 批准号: 7380804
• 负责人: D CHRISTIAN DERAUF
• 金额: $ 14.64万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7380804
• 关键词: METHAMPHETAMINE; CHILDREN

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A. Specific Aims Specific Aim 1: To identify the effects of prenatal MA exposure on CNS structure and metabolism in three year old children. Specific Aim 2: To examine the relationship between prenatal MA exposure, CNS structure and metabolism, and two cognitive domains, attention and arousal/self-regulation, assessed at 2 and 3 years of age. (The specific aims have not been modified). B. Studies and Results The PI is undertaking a cross-sectional neuroimaging study of three year-old children currently enrolled in the Hawai`i Infant Development, Environment and Lifestyle (IDEAL) study (RO1 DA 014948; Lester, PI). Prospectively collected data will include information about gestational MA and other drug exposure obtained at birth and one month of age, developmental, behavioral, and neuropsychologic measures obtained at 24 months and 36 months, and structural (3 Tesla MRI) and biochemical (1H MRS) neuroimaging data obtained at 36 months. For the neuroimaging studies, specific brain regions of interest (ROI) have been chosen a priori based upon existing preclinical and clinical studies looking at prenatal MA exposure and neurodevelopment. Other covariates measured as part of the IDEAL study include: (1) prenatal marijuana and tobacco exposure; (2) information related to maternal demographics; (3) information describing ongoing drug use, psychological status, parenting stress, intelligence, abuse potential, household conflict, and self-esteem; and (4) neighborhood characteristics assessed by caretaker-report and block group census data. Children who have a history of prenatal alcohol exposure will be excluded. Three cohorts will be recruited: Cohort 1 - those children exposed prenatally to MA and tobacco; Cohort 2 - children exposed prenatally to tobacco; and Cohort 3 - children exposed prenatally to neither MA nor tobacco. With regard to Specific Aim 1, the following progress to date has occurred: 1) the PI has obtained IRB approvals from both institutions where the study procedures will occur (Hawaii Pacific Health and Queens Medical Center), and a Certificate of Confidentiality has been obtained from the DHHS; 2) the MRI protocols needed for the study have been developed and piloted on two volunteer 3 year-old subjects; 3) the PI and the Study Coordinator identified other researchers at mainland institutions with experience scanning unsedated 3 year-old children, and received hands-on training at Johns Hopkins University to learn operant conditioning behavioral techniques to help preschool-aged children comply with the MRI/MRS procedure (a major criticism of the study design by the NIDA-K Training and Development Subcommittee (along with other review groups) was that 3 year-old children might differ greatly in their ability to comply with holding still for the neuroimaging, and that this ability might vary by MA exposure status - therefore, considerable effort was made to learn techniques to improve the overall compliance of all enrolled children); 4) one IDEAL study 3 year-old subject was successfully scanned; 8 additional IDEAL subjects have been consented and are being scheduled for study procedures; an additional 30 IDEAL subjects are eligible through May 2006, but are still pending their 36 month IDEAL study visit, at which time the neuroimaging study will be introduced. Regarding Specific Aim 2, the following progress to date has occurred: 1) considerable time has been spent by the PI developing a working knowledge of Developmental Psychology and Developmental Psychopathology, given that his background as a general pediatrician has provided little background knowledge of these subjects. This training has involved extensive reading of textbooks and peer-reviewed articles, mentor meetings with Dr. Barry Lester (the designated mentor for this topical area), conference attendence, and presentations of the PI¿s progress at JABSOM research forums; 2) the PI identified a mainland consultant with expertise in executive function testing of preschool-aged children. This consultant visitied UH on April 18th, 2006, and has provided ongoing consultation with the PI. Together with this person, the PI has developed a new battery of neuropsychological measures for Specific Aim 2. Given the preliminary stage of implementation of the research study described above, no results are available for this progress report. C. Significance Multiple questions remain unanswered about how extent and timing of MA exposure and co-exposure to prenatal tobacco and marijuana impact these neurobiological alterations, and whether these alterations ultimately relate to disorders in child behavior. Studies that elucidate the relationships between prenatal drug exposure, neurobiological development and human behavior are critical to support the development of strategies that provide optimal care to at-risk children, and have been identified as a priority area for NIDA. The proposed study will examine the interplay between gestational MA exposure, brain morphology (structural MRI) and chemistry (1H-MRS), and two cognitive domains, attention and arousal/self-regulation. The project is important because it has the potential of advancing our knowledge about how drugs of abuse may impact the developing nervous system. Additionally, the project is important because it applies sophisticated neuroimaging techniques to the study of the largest prospectively followed cohort of children exposed to MA, an increasing important problem facing many communities in the U.S. D. Plans There are no anticipated changes regarding the involvement of Human Subjects or the use of Vertebrate Animals. The major goal of the upcoming year will be the enrollment of subjects and the successful implementation of the research protocol described above. The PI also plans to develop a pilot research proposal examining polymorphisms in dopamine and serotonin genes, in order to begin to assess the relationship of these genetic markers with the neurodevelopment of MA exposed children.

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。A.具体目的具体目的1：确定产前MA暴露对三岁儿童中枢神经系统结构和代谢的影响。具体目的2：研究产前MA暴露，中枢神经系统结构和代谢，以及两个认知领域，注意力和觉醒/自我调节之间的关系，在2岁和3岁时进行评估。（具体目标没有修改）。B.研究和结果PI正在对目前参加夏威夷婴儿发育、环境和生活方式（IDEAL）研究（RO1 DA 014948; Lester， PI）的三岁儿童进行横断面神经影像学研究。前瞻性收集的数据将包括出生和1月龄时获得的妊娠MA和其他药物暴露信息，24月龄和36月龄时获得的发育、行为和神经心理测量，以及36月龄时获得的结构（3特斯拉MRI）和生化（1H MRS）神经影像学数据。对于神经成像研究，特定的感兴趣的大脑区域（ROI）已经根据现有的临床前和临床研究来选择，这些研究着眼于产前MA暴露和神经发育。IDEAL研究中测量的其他协变量包括：(1)产前大麻和烟草暴露；（二）孕产妇人口统计资料；(3)药物使用现状、心理状况、养育压力、智力、虐待倾向、家庭冲突和自尊等信息；(4)利用看护者报告和街区组普查数据评估社区特征。有产前酒精暴露史的儿童将被排除在外。将招募三个队列：队列1 -产前暴露于MA和烟草的儿童；队列2——产前接触烟草的儿童；队列3——产前既不接触MA也不接触烟草的儿童。关于具体目标1，迄今为止已取得以下进展：1)PI已获得研究程序将进行的两个机构（夏威夷太平洋卫生和皇后医疗中心）的IRB批准，并已从国土安全部获得保密证书；2)研究所需的核磁共振成像方案已经在两名3岁的志愿者身上进行了开发和试点；3)项目负责人和研究协调员在内地机构找到其他有扫描未注射镇静剂的3岁儿童经验的研究人员；并在约翰霍普金斯大学接受实践培训，学习操作性条件反射行为技术，以帮助学龄前儿童遵守MRI/MRS程序(NIDA-K培训和发展小组委员会（以及其他审查小组）对研究设计的主要批评是，3岁儿童在遵守神经成像保持静止的能力方面可能存在很大差异，并且这种能力可能因MA暴露状态而异-因此，为学习提高所有登记儿童总体依从性的技术作出了相当大的努力)；4)成功扫描1名IDEAL研究3岁受试者；另外8名IDEAL受试者已获得同意并正在安排研究程序；另外30名IDEAL受试者在2006年5月之前符合条件，但仍在等待他们36个月的IDEAL研究访问，届时将介绍神经影像学研究。关于具体目标2，到目前为止已经取得了以下进展：1)PI花了相当多的时间来发展发展心理学和发展精神病理学的工作知识，考虑到他作为普通儿科医生的背景对这些学科的背景知识知之甚少。培训内容包括广泛阅读教科书和同行评议文章，与Barry Lester博士（该主题领域的指定导师）举行导师会议，参加会议，并在JABSOM研究论坛上介绍PI的进展；2)在内地物色一位具有学前儿童执行功能测试专业知识的顾问。该顾问于2006年4月18日访问了UH，并与PI提供了持续的咨询。与这个人一起，PI开发了一套新的神经心理学测量方法，用于特定目标2。鉴于上述研究的初步实施阶段，本进度报告没有任何结果。关于MA暴露的程度和时间以及产前烟草和大麻的共同暴露如何影响这些神经生物学改变，以及这些改变最终是否与儿童行为障碍有关，许多问题仍未得到解答。阐明产前药物暴露，神经生物学发育和人类行为之间关系的研究对于支持为高危儿童提供最佳护理的策略的发展至关重要，并且已被确定为NIDA的优先领域。该研究将检查妊娠期MA暴露、脑形态学（结构MRI）和化学（1H-MRS）以及两个认知领域（注意力和觉醒/自我调节）之间的相互作用。这个项目很重要，因为它有可能提高我们对滥用药物如何影响发育中的神经系统的认识。此外，该项目很重要，因为它将复杂的神经成像技术应用于对暴露于MA的儿童进行最大的前瞻性随访队列的研究，MA是美国许多社区面临的一个日益重要的问题。计划在涉及人类受试者或使用脊椎动物方面没有预期的变化。即将到来的一年的主要目标将是受试者的登记和上述研究方案的成功实施。PI还计划制定一项试点研究计划，检查多巴胺和血清素基因的多态性，以便开始评估这些遗传标记与暴露于MA的儿童神经发育的关系。