The genetic basis for caffeine-induced anxiety discovered

December 08, 2002

Most people find caffeine stimulating - Americans alone consume about 350 million cups of coffee daily. But some people find that it makes them anxious instead.

A recently completed study sheds new light on the likely reason for this difference. Individuals who have two linked genetic variations are far more likely to end up biting their nails following a jolt of caffeine than those who don't, reported Harriet de Wit of the University of Chicago on Sunday, Dec. 8 at the annual meeting of the American College of Neuropsychopharmacology held in San Juan, Puerto Rico.

"This is the first time that anyone has identified why people have different behavioral reactions to the same drug," said de Wit.

In addition to providing new information on why this commonplace drug affects some people differently than others, the results validate a methodology that should be capable of identifying individual differences in how people respond to a number of major drugs, she said.

Researchers from the University of Chicago and two German universities, M?nster and Würzburg, recruited 94 healthy, infrequent users of caffeine. In a double-blind study, the researchers administered oral doses of caffeine or placebo and then recorded their physiological reactions and subjective mood states.

The researchers also took blood samples from the participants and investigated the genes that code for two proteins, called adenosine receptors, which are known to interact with caffeine. Receptors form special features on the surface of nerve cells that bind with specific neurotransmitters, in this case adenosine, and affect the nerve's internal processes. One of these receptors, A1, is widely distributed throughout the brain while the other, A2a, is concentrated in the basal ganglia, a region deep below the cerebral cortex in the middle of the brain.

The researchers observed four genetic variations of the adenosine receptor genes in their group. When they analyzed their results, they found that individuals who had two specific variants in the A2a receptor gene exhibited much higher levels of anxiety after ingesting caffeine than those with other versions of the gene.

These results were consistent with previous studies that found people who suffer from a condition called panic disorder are likely to have one of the same variants and that, among those suffering from this condition, caffeine consumption is likely to bring on panic attacks.

Other than increased anxiety levels, this group, about 30 percent of the participants, had the same basic reactions to caffeine as the others, including feelings of stimulation, increased heart rate and faster-than-normal performance of psychomotor tasks.

De Wit and her colleagues have plans to use the same approach to study individual differences in reaction to amphetamine.
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Co-authors of the study are Karen Alsene from the University of Chicago, Jurgen Deckert from the University of M?nster and Philipp Sand from the University of Würzburg. The research was funded by the National Institute on Drug Abuse and Innovative Medizinische Forschung of the University of M?nster.

The American College of Neuropsychopharmacology (ACNP) is a professional organization of some 600 leading scientists that was founded in 1961. Members are selected primarily on the basis of their original research contributions to the field of neuropsychopharmacology, which involves the evaluation of the effects of natural and synthetic compounds on the brain, mind and human behavior. The principal functions of the College are research and education. ACNP's annual meeting is limited to participants from around the world who have made major research or clinical contributions in the field.

American College of Neuropsychopharmacology

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