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Anxious about coffee?

Not everyone can tolerate coffee; in some people the caffeine can even trigger symptoms of anxiety. This is down to a small variant in their genetic make-up. Its effect can however be mitigated through regular coffee consumption.

Coffee is and remains the drink of choice for German people. They drank 1.3 billion cups last year, according to the German Coffee Association. In other words, every German person enjoyed an average of 150 liters of coffee over the course of the year.

What makes drinks such as coffee and tea, and indeed cola and cocoa, so popular worldwide is, more than anything else, their stimulating effect. But it is an effect that causes discomfort in other people: after having drinks containing caffeine they feel their heart racing, break out in a sweat, feel restless, and have trouble going to sleep; many of them also experience anxiety for no specific reason. This is why patients who suffer from anxiety disorders often give up coffee or reduce their consumption.

Würzburg scientists under psychiatrist Professor Jürgen Deckert, working with a team led by Peter Rogers from the University of Bristol, have now discovered that the extent of this anxiety also depends on how regularly coffee is consumed. Their work is reported on in the latest issue of the journal Neuropsychopharmacology.

Alterations in genetic make-up are the trigger

Alterations in genetic make-up are the reason why some people react anxiously to a cup of coffee or tea. "We managed to show that a variant in the gene of the adenosine A2A receptor plays a key role in this process," says Jürgen Deckert. Normally, the transmitter adenosine docks onto this receptor in certain areas of the brain, triggering a relaxing response. However, if the receptor gene has been altered, caffeine can displace the adenosine and thereby prevent its relaxing effect.

However, for this to happen, persons affected must carry the altered gene on both their father's and their mother's chromosome. "In a study on volunteers in collaboration with Harriet de Wit's team from the University of Chicago, we established that only those subjects who possessed the same gene variants on the long arm of both chromosomes 22 reacted with anxiety to an average dose of caffeine," says Deckert. This effect, like the stimulating effect of caffeine, was temporary; over time it subsided and after a few hours it had faded completely.

It depends on the dose

The anxious response only occurred, however, when the subjects consumed an average dose of caffeine - namely 150 milligrams, which equates to roughly two cups of coffee. With a lower dose (50 milligrams) none of the subjects reacted with anxiety, whereas with a higher dose (400 milligrams) every single one of them demonstrated elevated anxiousness - according to the findings of a further study with scientists from the University of Chicago. The genetic variation is therefore only relevant for the development of anxiety when the dose is in the average range.

"The findings are not surprising. Similar outcomes can be observed in other areas too," says Deckert. One example: usually nobody watching a romantic film experiences fear, but with a horror film everyone does. With the "average dose" - a thriller - only those who are sensitive in this way feel anxiety. Regular consumption has a desensitizing effect But people who react anxiously to coffee do not have to do so for the rest of their lives. "In our latest study together with Peter Rogers from the University of Bristol, we explored the issue of whether the level of daily coffee consumption by the subjects has an impact on the gene effect," says Deckert. It emerged that the gene effect is less pronounced in people who regularly consume an average or high dose of caffeine. In other words: "The inherited intolerance can probably be reduced by gradually increasing the dose and consuming it regularly," says the medic. Deckert sees the findings of these studies as further proof of how complex gene-environment interactions can be.

The connection with anxiety disorders

The same genetic variant that leads to increased anxiety after consuming caffeine was identified a few years back as a genetic risk variant for anxiety disorders by the Würzburg researchers in collaboration with researchers from the University of Bonn led by Markus Nöthen. Though it is unlikely that it can be the cause of an anxiety disorder by itself. "This undoubtedly also requires environmental factors, such as the consumption of caffeine or traumatic life events," states Jürgen Deckert.

These complex interactions between caffeine and other substances impacting indirectly on the adenosine A2A receptor are currently being examined by the Würzburg researchers in collaboration with a team from Münster led by Katharina Domschke within the scope of the Collaborative Research Center SFB TRR 58 "Fear, Anxiety, Anxiety Disorders".

The project still needs volunteers. Subjects should be healthy and between the ages of 18 and 65. Anyone who is interested should call +49 (0)931 312687 or e-mail mega@psychologie.uni-wuerzburg.de

"Association of the Anxiogenic and Alerting Effects of Caffeine with ADORA2A and ADORA1 Polymorphisms and Habitual Level of Caffeine Consumption", Peter J Rogers, Christa Hohoff, Susan V Heatherley, Emma L Mullings, Peter J Maxfield, Richard P Evershed, Jürgen Deckert and David J Nutt. Neuropsychopharmacology (2010) 35, 1973-1983, doi:10.1038/npp.2010.71


Prof. Dr. Jürgen Deckert, Department of Psychiatry, Psychosomatics and Psychotherapy, T: +49 (0)931 201 77 000, e-mail: deckert_j@klinik.uni-wuerzburg.de

idw :: 20.08.2010

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