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Reward Deficiency Syndrome

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

In 1990 one of us published with his colleagues a paper suggesting that a specific genetic anomaly was linked to alcoholism (Blum et al. 1990). Unfortunately it was often erroneously reported that they had found the "alcoholism gene," implying that there is a one-to-one relation between a gene and a specific behavior. Such misinterpretations are common-readers may recall accounts of an "obesity gene," or a "personality gene." Needless to say, there is no such thing as a specific gene for alcoholism, obesity or a particular type of personality. However, it would be naive to assert the opposite, that these aspects of human behavior are not associated with any particular genes. Rather the issue at hand is to understand how certain genes and behavioral traits are connected.

In the past five years we have pursued the association between certain genes and various behavioral disorders. In molecular genetics, an association refers to a statistically significant incidence of a genetic variant (an allele) among genetically unrelated individuals with a particular disease or condition, compared to a control population. In the course of our work we discovered that the genetic anomaly previously found to be associated with alcoholism is also found with increased frequency among people with other addictive, compulsive or impulsive disorders. The list is long and remarkable-it comprises alcoholism, substance abuse, smoking, compulsive overeating and obesity, attention-deficit disorder, Tourette's syndrome and pathological gambling.

Spectrum of Disorders

We believe that these disorders are linked by a common biological substrate, a "hard-wired" system in the brain (consisting of cells and signaling molecules) that provides pleasure in the process of rewarding certain behavior. Consider how people respond positively to safety, warmth and a full stomach. If these needs are threatened or are not being met, we experience discomfort and anxiety. An inborn chemical imbalance that alters the intercellular signaling in the brain's reward process could supplant an individual's feeling of well being with anxiety, anger or a craving for a substance that can alleviate the negative emotions. This chemical imbalance manifests itself as one or more behavioral disorders for which one of us (Blum) has coined the term "reward deficiency syndrome."

This syndrome involves a form of sensory deprivation of the brain's pleasure mechanisms. It can be manifested in relatively mild or severe forms that follow as a consequence of an individual's biochemical inability to derive reward from ordinary, everyday activities. We believe that we have discovered at least one genetic aberration that leads to an alteration in the reward pathways of the brain. It is a variant form of the gene for the dopamine D2 receptor, called the A1 allele. This is the same genetic variant that we previously found to be associated with alcoholism. In this review we shall look at evidence suggesting that the A1 allele is also associated with a spectrum of impulsive, compulsive and addictive behaviors. The concept of a reward deficiency syndrome unites these disorders and may explain how simple genetic anomalies give rise to complex aberrant behavior.

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The Biology of Reward

The pleasure and reward system in the brain was discovered by accident in 1954. The American psychologist James Olds was studying the rat brain's alerting process, when he mistakenly placed the electrodes in a part of the limbic system, a group of structures deep within the brain that are generally believed to play a role in emotions. When the brain was wired so that the animal could stimulate this area by pressing a lever, Olds found that the rats would press the lever almost nonstop, as many as 5,000 times an hour. The animals would stimulate themselves to the exclusion of everything else except sleep. They would even endure tremendous pain and hardship for an opportunity to press the lever. Olds had clearly found an area in the limbic system that provided a powerful reward for these animals.

Research on human subjects revealed that the electrical stimulation of some areas of the brain (the medial hypothalamus) produced a feeling of quasi-orgasmic sexual arousal (Olds and Olds 1969). If certain other areas of the brain were stimulated, an individual experienced a type of light-headedness that banished negative thoughts. These discoveries demonstrated that pleasure is a distinct neurological function that is linked to a complex reward and reinforcement system (Hall, Bloom and Olds 1977).

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