6,7 However, while these designs demonstrate that drug-dependence disorders

are familial, they cannot distinguish between genetic and environmental contributions to this familiality. A demonstration of genetic contributions to these and other disorders requires other designs, prominently twin and adoption studies. Two adoption studies conducted by Cadoret et al8,9 showed that the only biological factor that was significantly associated with drug abuse in the proband was an alcohol problem in first-degree relatives. However, Tsuang et al,10 Inhibitors,research,lifescience,medical studying a sample of more than 3000 twin pairs, found a significantly greater pairwise concordance rate for monozygotic (MZ) than dizygotic (DZ) twins for abuse of marijuana, stimulants, cocaine, and for all drugs combined. Using twin pairs ascertained through the Virginia Twin Registry, Kendler et al examined concordance rates for drug use and dependence Inhibitors,research,lifescience,medical among more than 800 NVP-BGJ398 molecular weight female-female pairs.11-13 Model

fitting showed that twin Inhibitors,research,lifescience,medical resemblance for liability to the use of cocaine, cannabis, hallucinogens, opioids, and sedatives was due to both genetic and family environmental factors. Liability to abuse or dependence on cocaine and cannabis was due only to genetic factors. In contrast, however, in another study by Kendler et al14 of the use and misuse of six classes of illicit drugs by nearly 1200 male-male twin pairs, model fitting revealed that one common genetic factor exerted a potent influence on risk for both substance use and misuse for all six substances. Inhibitors,research,lifescience,medical There was a modest effect on risk of substancespecific genetic factors seen for substance use, but in contrast to other studies cited above, not for abuse or dependence. Inhibitors,research,lifescience,medical A single common shared environmental factor was also found to exert an effect on risk of substance use, and to a lesser extent, on risk of abuse dependence. Despite some contradictory findings, overall, the data from adoption, twin, and family studies support a substantial

genetic contribution to drug dependence, including the existence of genetic factors specific to each of these disorders, and factors common to these disorders and other forms of substance dependence. It is only common genetic factors (that is, those that influence more than one substance) that are likely to be important worldwide (genetic Rolziracetam factors specific to substances will vary because the specific substances vary). Whether genes relevant to drugs of abuse that have some similarities in their mechanisms of action, such as cocaine (important, eg, in the US) and methamphetamine (predominant, eg, in Thailand, and important in certain regions in the US) will prove to overlap, is still an open question. Further, different risk factors may be important in different populations (discussed in ref 1).