articles

Reward Deficiency Syndrome

Kenneth Blum, John G. Cull, Eric R. Braverman
and David E. Comings

cont.

D2 Receptor Gene

Since our 1990 study, some laboratories have failed to find a connection between the A1 allele and alcoholism. However, a review of their work shows that their samples were not limited to severe forms of alcoholism, which we believe to be an important distinguishing criterion. In our original study, over 70 percent of the alcoholics had cirrhosis of the liver, a disease suggestive of severe and chronic alcoholism. Moreover, the negative studies failed to adequately assess controls to eliminate alcoholism, drug abuse and other related "reward behaviors." In this regard, Katherine Neiswanger and Shirley Hill of the University of Pittsburgh recently found a strong association of the A1 allele and alcoholism and suggested that early failures were the result of poor assessment of a true phenotype in the controls (Neiswanger, Kaplan and Hill 1995). To date, 14 independent laboratories have supported the finding that the A1 allele is a causative factor in severe forms of alcoholism, though perhaps not in milder forms (Blum and Noble 1994). These findings do not prove that the A1 allele of the dopamine D2 receptor gene is the only cause of severe alcoholism, but they are a powerful indication that the A1 allele is involved with alcoholism.

DNA Fingerprint

Further evidence for the role of biology in alcoholism comes from efforts to find electrophysiological markers that might indicate a predisposition to the addictive disorder. One such marker is the latency and the magnitude of the positive 300-millisecond (P300) wave, an indicator of the general electrical activity of the brain that is evoked by a specific stimulus such as a tone. It turns out that abnormalities in the electrical activity of the brain are evident in the young sons of alcoholic fathers. Their P300 waves are markedly reduced in amplitude compared to the P300 waves of the sons of nonalcoholic fathers. These results raised the question as to whether this deficit had been transferred from father to son and whether this deficit would predispose the son to substance abuse in the future (Begleiter, Porjexa, Bihari and Kissin 1984).

Experiments carried out since then have answered both questions. The alcoholic fathers had the same P300-wave deficit seen in their sons, and the sons showed increased drug-seeking behaviors (including alcohol and nicotine) compared to the sons of nonalcoholic fathers. Moreover, the sons of alcoholic fathers had an atypical neurocognitive profile (Whipple, Parker and Noble 1988). It now appears that children with P300 abnormalities are more likely to abuse drugs and tobacco in later years (Berman, Whipple, Fitch and Noble 1993).

Remarkably, Noble and his colleagues found an association between the A1 allele and a prolonged latency of the P300 wave in children of alcoholics (Noble et al. 1994). Two of us (Blum and Braverman) extended this work and observed a similar correlation between the A1 allele and a prolonged P300 latency in a neuropsychiatric population. Subjects who are homozygous for the A1 allele showed significantly prolonged P300 latency compared to A1/A2 and A2/A2 carriers.

P300

Drug Addiction and Smoking

advertisement

Cocaine can bring intense, but temporary, pleasure to the user. The aftermath is addiction and severe psychological and physiological harm. Various psychosocial theories have been advanced to account for the abuse of cocaine and other illicit drugs. In contrast to alcoholism, where growing empirical evidence is implicating hereditary factors, relatively little has been known about the genetics of human cocaine dependence. However, some recent studies have suggested that hereditary factors are involved in the use and abuse of cocaine and other illicit drugs.

Studies of adopted children, for example, show that a biological background of alcohol problems in the parents predicts an increased tendency toward illicit drug abuse in the children (Cadoret, Froughton, O'Gorman and Heywood 1986). Similarly, family studies of cocaine addicts show a high percentage of first- or second-degree relatives who have been diagnosed as alcoholics (Miller, Gold, Belkin and Klaher 1989; Wallace 1990).

top | continued | table of contents

home | about me | diagnosis | behaviors | faqs | personal stories | parenting
education | workplace | articles | humor | resources |