Considerable research has been directed towards assessing the long-term consequences of illicit drug abuse, but little definitive information is available because of difficulties in distinguishing causes of drug abuse from effects. Observed differences might reflect either the consequences of drug abuse or a vulnerability to drug abuse that predated drug usage. This case-control study will evaluate the long-term impact of drug abuse on brain function by capitalizing on our epidemiological sample of over 8,000 twins from the Vietnam Era Twin Registry who have been interviewed by us within the last three years about their drug use history. We will compare twins who previously abused drugs to their co-twins who have never abused drugs. We propose to study the two most frequently abused categories of drugs in our sample, marijuana and stimulants (amphetamine & cocaine). We define abuse as the regular use of the drug (i.e., at least once per week) for at least one year. This definition identifies subjects with substantial histories of use (for marijuana: median length of regular use = 8 years, median days/week of use = 7; for stimulants: median length of regular use = 3 years, median days/week of use = 4). Subjects who have abused drugs other than marijuana or stimulants or experienced tolerance or withdrawal to alcohol will be excluded. Non-abusers never used any drug more than five times in their lives. Because marijuana is the most frequently abused illicit drug, our sample includes enough monozygotic pairs to comprise a sample of discordant pairs (n= 118 pairs) adequate for testing differences between abusers and non-abusers. Stimulant abuse is less prevalent, so there are fewer discordant monozygotic pairs available for study (n=69 pairs). Therefore, for stimulants we will supplement the discordant monozygotic pairs with discordant dizygotic pairs (n=55 pairs). A projected individual response rate of 76% will yield a total sample of approximately 141 pairs in which both twins participate. We will compare former drug abusers to their drug non-abusing co-twins in a classic epidemiological matched pair design. The goal of the study is to determine if marijuana and/or stimulants have long-term consequences on brain function as reflected in neuropsychological performance (memory, attention, problem solving, executive functions, etc.), electrophysiology (in a subset of monozygotic twins discordant for stimulant abuse), psychiatric status (Axis I and II psychopathology), and personality. We will also investigate dose-response relationships between the drugs and brain function, the possible role of age of initiation, and recovery of functioning. The consequences of marijuana will be compared to the consequences of stimulants. Twins from the discordant pairs will travel to one of the collaborating sites (Harvard Univ., Washington Univ., or Univ. of Illinois) or he visited in their home city for the administration of structured interviews, neuropsychological testing, and self-report measures. Those pairs participating in electrophysiological assessment will travel to the Harvard site.
| Tsai, Melyssa; Mori, Alaina M; Forsberg, Christopher W et al. (2013) The Vietnam Era Twin Registry: a quarter century of progress. Twin Res Hum Genet 16:429-36 |
