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Alcohol changes the brain

Alcoholics Anonymous, the twelve-step model. That’s how to stop alcoholics drinking, isn’t it?
However the model’s success rate remains modest. Instead, many researchers are now searching for medicines that prevent cravings. One of these researchers is Markus Heilig, a world-renowned professor in psychiatry who, during autumn, will relocate his operations to the Faculty of Health Sciences at LiU (Hälsouniversitetet).

Markus Heilig“Alcoholism is comprised of a large, heterogeneous group of conditions. Those in the risk zone retain more than 50 % heritability which, in turn, interacts with their surrounds or environment,” says Heilig.

For the last seven years Heilig has been Chief and Clinical Director Office of the Chief for National Institute on Alcohol Abuse and Alcoholism (NIAAA), which is the alcohol research institute of the National Institutes of Health (NIH) in Bethesda, outside of Washington DC.

People lose control of their behaviour for various reasons, he explains.

  • Some are people who get an unusually intense kick from alcohol. They secrete an extremely strong dose of dopamine, which, in turn results in an intense reward. 
  • Others are people sensitive to stress, who then receive temporary relief by drinking alcohol. They escape their anxieties for a short time, but quickly end up in a vicious circle. Dependence is difficult to rid because of physical changes in the brain, even considering that common sense tells them to “quit!”

“When the body is subjected to alcohol over the long term, a plasticity is triggered in the brain. We’ve seen this in rats that became alcoholic. The alcohol is removed for four months, which is a large part of a rat’s lifespan. Yet they still retain changes in gene expression in their stress system. Alcohol profoundly changes the brain’s functions long-term.”

During his post-doctoral studies with the neurobiologist George F. Koob at the Scripps Institute in California, Heilig began to search for substances in the brain relating to alcohol-dependent behaviour. Continuing on from this, he now has two keen medicine candidates who have begun the long journey through the various stages of clinical trials.

“The pharmaceutical industry is moving away from psychiatry. The golden age of Prozac is dead. The patent will expire and financial rewards have ceased. Therefore we, in the academy, need to take certain responsibility for the development,” he says.

One path is based on a brain structure with the mysterious name of amygdala. The amygdala is the centre for emotions and it has been found that drinking alcohol results in an increase of the hormone CRT (corticotropin releasing factor). If a substance is added, for example neuropeptide Y, then negative feelings are neutralised, as is the desire to remove these negative feelings by drinking alcohol.

The other promising strategy is to block the path of substance P, a neurotransmitter that signals pain and stress. In a clinical study, 50 anxiety-ridden alcoholics were admitted to hospital for one month. Half of them were given a medicine, LY686017, which had been earlier tested against depression, and the other half formed a control group who only received an ineffectual placebo. The researchers then conducted blood tests, interviews, and neuroimaging and carefully observed their reactions.

The participants viewed images while they were in a magnetic resonance imager. Those administered the placebo displayed strong reactions in certain regions of the brain when shown disturbing pictures (for example, a car accident), but weak reactions to positive pictures of children and animals. The results were the opposite for those administered the actual medicine.

Heilig drew the conclusion that the study supports the hypothesis that LY686017 represses stress and negative feelings behind anxiety-driven alcohol dependence.

The magnetic resonance imager and its inherent possibilities for the study of brain processes (fMRI) has become an important tool in Heilig’s research. The equipment currently at the Center for Medical Image Science and Visualization (CMIV) was one of the decisive factors for Heilig when his family decided to return to Sweden and this led to him choose Linköping.

“When Faculty Dean Mats Hammar contacted me, it turned out that we agreed on many aspects of medical research such as; the importance of health care managers and universities moving in the same direction, the need to invest in psychiatry following two lost generations due to difficult job conditions. Additionally, there was a distinguished technical centre for medical imaging (CMIV) however the magnetic resonance imager they had at the time wasn’t sufficient. When the Wallenberg fund invested in the purchase of a new, powerful 3 Tesla camera, all the conditions were in place,” Heilig says.

His research in Linköping will further develop an earlier project:

  • Social stress as a factor for affective disorders and dependency disorders, from mice to men in fMRI. Collaboration with David Engblom and Bud Craig.
  • Treatment development – the search for molecules that play a role in these disorders.
  • Personalised medicine – people are different and react differently to the same treatment. Many medicines work for some people but not for others. One example is Naltrexone, which is registered for alcoholics. 15 % of patients have a gene that provides a good effect from the medicine, but for the other 85 % it is generally ineffective.

“We’re starting a psychiatric research division with eight beds. We’re now working on bringing over young researchers from LiU to NIAAA to give them training on our techniques. This spring, my colleague Annika Thorsell will visit Linköping as a lecturer and will take on the main responsibility for preclinical operations,” Heilig says.

Text: Åke Hjelm


Page manager: johan.jager@liu.se
Last updated: 2014-11-28