ADOLESCENT ALCOHOL ABUSE: A TWIN-STUDY PERSPECTIVE

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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.