Some individuals who use drugs become drug abusers - they continue taking drugs even though doing so causes serious problems in their lives. Others avoid abuse or addiction. By studying patterns of drug use in pairs of twins, NIDA-supported researchers are beginning to clarify the role that genes play in predisposing individuals to drug abuse.

If genes influence the risk for drug abuse, identical twin pairs, who share the same genes, will tend to be concordant-that is, both will abuse drugs or both will not abuse drugs.

"Twin studies explore the roles and interrelationship of genetic and environmental risk factors in the development of drug use, abuse, and dependence," says Dr. Naimah Weinberg of NIDA's Division of Epidemiology, Services, and Prevention Research.

In twin studies, researchers interview both members of identical (monozygotic) and fraternal (dizygotic) twin pairs, who typically are exposed to common environmental influences. If genes influence their risk for drug abuse, identical twin pairs, who share the same genes, will tend to be concordant-that is, both will abuse drugs or not abuse drugs. Fraternal twin pairs, on the other hand, are no more similar genetically than non-twin siblings, and so will be less concordant - there will be more pairs in which one twin abuses drugs and the other does not. By comparing the degree of concordance in identical and fraternal twins, researchers can estimate the extent to which genes influence vulnerability to drug abuse.

Marijuana and Cocaine Abuse Among Female Twins

NIDA-supported researchers Dr. Kenneth Kendler and Dr. Carol Prescott at the Medical College of Virginia in Richmond have examined the patterns of marijuana and cocaine use by female twins and found that genetic factors play a major role in the progression from drug use to abuse and dependence. The researchers interviewed 1,934 twins, ranging in age from 22 to 62, recruited from the Virginia Twin Registry, a database compiled from Commonwealth birth records.

Percentages of pairs in which both twins used, abused, or were dependent on marijuana or cocaine were higher in identical twins than in fraternal twins.

In the study, drug "use" involved at least one nonprescribed use of a drug; "abuse" was based on the definition provided in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), which includes symptoms such as recurrent use in situations where it presents a physical danger, failure to meet obligations at work or school, or recurrent social or interpersonal problems caused by effects of the drug; and "dependence" was based on the DSM-IV definition and included characteristics such as physical symptoms of tolerance or withdrawal, taking larger amounts of the drug or using it over a longer period than intended, or spending large amounts of time seeking, obtaining, and recovering from the effects of the drug.

"Our research supports other studies that indicate family and social environmental factors are influential in determining whether an individual begins using these drugs," Dr. Kendler says. "But our findings suggest that the progression from the use of cocaine or marijuana to abuse or dependence was due largely to genetic factors."

In addition, Dr. Kendler says, the study found that concordance rates-both twins using, abusing, or being dependent on drugs-were higher for identical than fraternal twins (see chart). For cocaine use, concordance was 54 percent in identical twins and 42 percent in fraternal twins; for abuse, 47 percent in identical twins and 8 percent in fraternal twins; and for dependence, 35 percent in identical twins and zero for fraternal twins.

"Abuse and dependence are highly heritable," Dr. Kendler says. "For both cocaine and marijuana, genetic factors are responsible for roughly 60 to 80 percent of the differences in abuse and dependence between fraternal and identical twin pairs."

Genetic Risk Factors Differ Among Drugs and Between Males and Females

Dr. Ming Tsuang, a NIDA-supported researcher at Harvard University in Cambridge, Massachusetts, has found that, in males, genetic influences are stronger for abuse of some drugs than for others. Dr. Tsuang and his colleagues studied drug use in 1,874 identical male twin pairs and 1,498 fraternal male twin pairs recruited from the Vietnam Era Twin Registry, a database compiled from Department of Defense records. The average age of participants was 45.

The researchers found evidence to suggest that genetic influences contribute to a common vulnerability for abusing marijuana, sedatives, stimulants, heroin or opiates, and psychedelics. "There is some characteristic of the individual that imparts vulnerability to the abuse of all categories of drugs. Abusing any category of drugs was associated with a marked increase in the probability of abusing every other category of drugs," Dr. Tsuang says. In addition to this shared vulnerability, the researchers found different vulnerabilities for different drugs. "Each category of drugs we looked at, except psychedelics, had unique genetic influences," Dr. Tsuang says. "The genetic influence for abuse was greater for heroin than for any other drug."

"The progression from the use of cocaine or marijuana to abuse or dependence was due largely to genetic factors."

NIDA-supported studies involving male and female twins suggest that genetic factors for drug abuse are stronger in males than in females. Dr. Marianne van den Bree and Dr. Roy Pickens of NIDA's Intramural Research Program and their colleagues studied 188 twin pairs in which at least 1 twin was recruited through a drug treatment program. The sample included 56 identical male pairs, 66 fraternal male pairs, 38 identical female pairs, and 28 fraternal female pairs. Participants were interviewed to determine drug use (five times or more) and clinical diagnosis (according to DSM criteria) of drug abuse, dependence, or both for sedatives, stimulants, opiates, marijuana, or cocaine. For most drugs, clinical diagnosis of abuse, dependence, or both was more strongly influenced by genetic factors than was drug use. In addition, for most drugs, genetic influences for abuse or dependence were greater for males than for females.

"For females, genetic influences accounted for 47 percent of the differences between identical and fraternal twins in abuse, dependence, or both for any drug, compared with 79 percent for males," Dr. van den Bree says. The impact of genetic factors also seems to differ for specific drugs, she notes. The researchers found no evidence for genetic influence for opiate or sedative abuse, dependence, or both in females, but in males genetic influences were generally larger than environmental influences.

"The results we see from these twin studies are making important advances in our understanding of the role of genetic influences in drug abuse," observes NIDA's Dr. Weinberg. "Although the studies can't tell us anything about the risk for a particular individual, they are of enormous value in helping define the variations in drug abuse vulnerability in the population."

Sources

American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders (4th Edition) Washington, DC: American Psychiatric Association, 1994.

Kendler, K., and Prescott, C. Cannabis use, abuse, and dependence in a population-based sample of female twins. American Journal of Psychiatry 155(8):1016-1022, 1998.

Kendler, K., and Prescott, C. Cocaine use, abuse, and dependence in a population-based sample of female twins. British Journal of Psychiatry 173:345-350, 1998.

Tsuang, M., et al. Co-occurrence of abuse of different drugs in men. Archives of General Psychiatry 55:967-972, 1998.

Van den Bree, M.; Johnson, E.; Neale, M.; and Pickens, R. Genetic and environmental influences on drug use and abuse/dependence in male and female twins. Drug and Alcohol Dependence 52(3):231-241, 1998.