ADOLESCENT ALCOHOL ABUSE: A TWIN-STUDY PERSPECTIVE

青少年酗酒：双胞胎研究的视角

• 批准号: 7101030
• 负责人: Richard Joseph Rose
• 金额: $ 28.98万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-06-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7101030
• 关键词: ADOLESCENT; ALCOHOL; ABUSE; TWIN; STUDY

The application for this research, submitted 03/99, was prepared in response to RFA AA-99-003; its fundamental aim was to study consequences and mechanisms of adolescent alcohol abuse, and those aims continue to guide our plans for this 5-year extension. The research plans build on two ongoing longitudinal twin-family studies conducted in Finland. One study, FinnTwin16, is of -2,800 twin pairs, born 1975-79; the twins and their parents were assessed by postal questionnaire, during 1991-95, as the twins reached age 16; follow-up assessments of the twins were made at ages 17, 18½, and, in work funded by this award, at ages 23-27. The fourth wave assessment has enabled us to study consequences of adolescent alcohol misuse on personal and social outcomes in early adulthood, and to select twin pairs extremely discordant and concordant (EDAC) for adolescent alcohol abuse for a laboratory protocol that includes extraction of DNA, a neuropsychological (NP) test battery, the Semi-Structured Assessment for Genetics of Alcoholism (SSAGA) interview, and measurement of EEG/ERP function. The laboratory protocol continues for 17 months with current funding, to reach a projected sample of >225 informative twin pairs. The Progress Report included in this extension application documents the rich informational value of our data and of our analytic strategy of combining epidemiological studies of twins, as individuals, with within-family analyses of discordant/concordant twin pairs. We plan to pursue and expand these studies during the next five years, focusing now on the younger FinnTwin12 cohorts, born 1983-87, on whom we have very rich anterospective data. We will retain the key elements of the current study protocol, so that we can combine data from drinking-discordant twin pairs, including all monozygotic twin pairs discordant for adolescent alcohol exposure, to gain power for analyses. The SSAGA interviews, the current NP test battery, and the laboratory protocol for evaluation of EEG/ERP will be retained in planned studies of FT12 twins as they reach comparable ages to the twins recruited for the research now ongoing. Starting early in 2005, as the 1983 twin birth cohort reaches age 22, we will initiate a questionnaire survey of all FT12 twins and of their parents. The mail outs will be staggered by the twins' birth dates, to assess all at ages 21-22. By mid-2005, we will begin interviews of >900 Stage-2 twin-families of FT12, scheduling abbreviated follow-up SSAGA interviews of parents (conducted by 'phone per COGA procedures) and more extensive interviews of twins. The interviews will be a 10-year follow-up of parents, a 7-8-year follow-up of twins, all of whom completed adolescent SSAGAs at age 14. We will arrange, via local community health centers, for the parents and twins to have blood draws, to be sent to the National Public Health Institute in Helsinki for extraction of DNA. By late-2005, with new grant monies available, we will start scheduling EDAC-selected twins, discordant for alcohol use at ages 12, 14,17, and 21-22, from the 1983 birth cohort for the laboratory protocol. We will expand our current research initiative in two directions. First, to exploit the richly informative data set of FT12, we will begin molecular genetic analyses, collaborating with laboratories in St. Louis (A. Goate) and Helsinki (L. Peltonen); we anticipate having DNA from N600 dizygotic twin pairs studied from ages 11-12 and from one, usually both, of their parents. Because data we have on these twins is unusually rich, with baseline assessments from multiple informants (teachers, parents, peers, self and co-twin) and with repeated, structured interviews of both twins and their parents, the data will offer robust, constructive replication of COGA's genetic findings, and, with consultation/collaboration of Prof. Goate, we are positioned to perform those replication efforts very efficiently and effectively. Second, studying the FT12 twins, we will enrich our current data on neurobiological mechanisms and consequences of alcohol abuse in adolescence: We plan to repeat collections of saliva for assays of testosterone, cortisol, and estradiol on the '86-87 FT12 cohorts, at an 8-year interval, for data that will be very informative of consistency and change in these assays over time; we also plan exploratory studies of fMRI BOLD response of cue-reactivity and craving after cue-exposure in a small and highly selected subset of twins, including MZ pairs, to study physiological response and cognitive appraisals to alcohol stimuli in informative co-twins selected for their history of adolescent drinking-discordance.

这项研究的申请书提交了03/99，是根据RFA AA-99-003的要求编写的；其 基本目的是研究青少年酗酒的后果和机制，以及 这些目标继续指导我们这次五年延期的计划。研究计划建立在两个基础上 芬兰正在进行的纵向双胞胎家庭研究。一项名为FinnTwin16的研究是-2800 双胞胎出生于1975-79年；这对双胞胎和他们的父母在 1991年至1995年，这对双胞胎年满16岁；17岁时对双胞胎进行了后续评估， 18/5岁，在该奖项资助的工作中，年龄为23-27岁。第四波评估已启用 美国将在早期研究青少年酗酒对个人和社会结果的影响 成年，并为青少年选择极不协调和协调的双胞胎(EDAC) 酒精滥用的实验室方案，包括提取DNA，神经心理(NP)测试 Batch，酒精中毒遗传学半结构化评估(SSAGA)访谈，以及 脑电/事件相关电位功能测定。实验室方案持续了17个月，目前 资金，以达到预测样本&gt；225对信息丰富的双胞胎。进度报告包括 在此扩展应用程序中，记录了我们的数据和分析的丰富信息价值 双胞胎作为个体的流行病学研究与家庭内分析相结合的战略 不协调/协调的双胞胎。我们计划在未来五年继续并扩展这些研究。 几年来，现在关注出生于1983-87年的年轻芬兰双胞胎12人，我们对他们有非常丰富的了解 前瞻数据。我们将保留目前研究议定书的主要内容，以便我们能够 合并来自饮酒不和谐双胞胎的数据，包括所有不和谐的同卵双胞胎 青少年酒精暴露，以获得分析能力。SSAGA面试，目前的NP测试 电池，评估脑电/事件相关电位的实验室方案将在计划的研究中保留 FT12双胞胎的年龄与目前正在进行的研究中招募的双胞胎年龄相当。 从2005年初开始，随着1983年出生的双胞胎年龄达到22岁，我们将启动一份问卷调查 对所有FT12双胞胎及其父母的调查。这对双胞胎的出生日期会让邮寄的时间错开， 在21-22岁对所有人进行评估。到2005年年中，我们将开始采访&gt；900阶段-2双胞胎家庭 FT12，安排对家长的简短后续SSAGA访谈(由电话Per进行 COGA程序)和更广泛的双胞胎访谈。这些采访将是为期10年的后续行动 父母，对双胞胎进行了7-8年的跟踪调查，他们都在14岁时完成了青少年SSAGA。 将通过当地社区卫生中心安排父母和双胞胎抽血， 被送到赫尔辛基的国家公共卫生研究所提取DNA。到2005年末，有了新的 有钱可用，我们将开始安排EDAC挑选的双胞胎，不和谐的酒精使用在 年龄分别为12岁、14岁、17岁和21-22岁，来自1983年实验室方案的出生队列。 我们将在两个方向上扩展我们目前的研究计划。首先，开发信息丰富的 FT12的数据集，我们将开始分子遗传分析，与圣路易斯的实验室合作 (A.Goate)和赫尔辛基(L.Peltonen)；我们预计有来自N600双卵双胞胎的DNA 从11岁到12岁，从父母中的一个人，通常是两个人那里学习。因为我们有关于这些的数据 双胞胎非常丰富，有来自多个告密者的基线评估(教师、父母、同龄人、 通过对双胞胎和他们的父母进行重复的、结构化的采访，数据将 提供对COGA基因研究结果的有力、建设性的复制，并与咨询/合作 在Goate教授的领导下，我们能够非常高效地进行这些复制工作。 第二，研究FT12双胞胎，我们将丰富我们目前关于神经生物学机制和 青少年酗酒的后果：我们计划重复收集唾液进行检测 ‘86-87 FT12队列中的睾酮、皮质醇和雌二醇，每隔8年，数据将 对这些分析的一致性和随时间的变化提供非常丰富的信息；我们还计划进行探索性 小线索暴露和高线索暴露后线索反应性和渴求的fMRI大胆反应研究 选定的双胞胎子集，包括MZ对，用于研究生理反应和认知评估 根据青少年饮酒史选择的信息丰富的同卵双胞胎对酒精刺激的反应。