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Introducing Lukas Pezawas: Pioneering Research with "Imaging Genetics" on Genetic Factors in Depression

bridges vol. 6, July 2005 / News from the Network
by Caroline Adenberger

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 When Lukas Pezawas returned to Austria to become Director of the ambulatory care unit for the Clinical Department of General Psychiatry at the Medical University of Vienna (MUV), he did not return empty-handed but with a briefcase full of very promising research results. After three years of research at the renowned US National Institute of Mental Health (NIMH), he is now eager to apply them at his new - and former - home base in Vienna.


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Back in 1992, while still a medical student in Vienna, Lukas Pezawas had the opportunity to participate in an elective course with Prof. Oleh Hornykiewicz, a leading scientist in brain research, and once nominated for the Nobel Prize. Hornykiewicz was also the one who encouraged Pezawas to go abroad, and helped him to get a summer internship at the Maryland Psychiatric Research Center in Baltimore. This experience in the US impressed Pezawas so much that he decided to return to the US after completing his studies in Vienna. In 2001 he finished his training as a medical specialist in psychiatry and started working as a senior physician in the Clinical Department of General Psychiatry at the Medical University of Vienna. Only six months later, with the support of Prof. Siegfried Kasper, head of the Clinical Department of General Psychiatry at the MUV, Pezawas received a second opportunity to do research in the US - this time at the National Institute of Mental Health, one of the institutes of NIH.

When Pezawas started as a postdoctoral research fellow at NIMH, he was supported by a Schrödinger Fellowship from the Austrian Science Fund (FWF). After his first year of research, the FWF asked for a progress report, but the initial research results had not reached a point where they could be shown. "In Austria," Pezawas explains, "research sometimes means something very different than in the US. To conduct a research project at NIH, for example, takes an average of two to three years before you obtain reliable data that you want to publish. That's nothing new here; no one would expect reputable data any earlier. But in Austria, where 'research' sometimes doesn't mean anything beyond comparing existing data, those 'research results' were expected after a very short period of time."


Ineligible for Austrian funding, but good enough for a position at the NIH
As a result of the "lack of output" from his research, the FWF decided not to continue the fellowship for a second year. "It was a very frustrating experience," Pezawas remembers. "One week before Christmas, I received the e-mail from the FWF bluntly telling me that, they are going to cancel my grant within one month."


But what first appeared to be bad luck turned into good luck: Dr. Daniel Weinberger, program director at NIMH and, at this time, Lukas Pezawas' boss, recognized the potential of the young researcher and his work - and offered him a position on his team. It was a good decision. Only one year later, in 2003, Pezawas was leading his own research group with a focus on imaging genetics, supported by three additional research assistants. Asked about his feelings when he looks back at the FWF decision, Pezawas says, "I don't look back in anger. At that time, many colleagues of mine had to face the same situation. I think it was probably due to general financial difficulties with funding research projects because of a small funding budget. But - and this is a matter of fact - if the NIH hadn't kind of stepped into the breach and made it possible for me to continue my research, we wouldn't have the results and knowledge we have today."

Pezawas' paradigm shift in psychiatry

The results of Pezawas' research team are quite remarkable: They found their way not just into the world's leading journal for brain research, Nature Neuroscience, but also into the headlines of leading newspapers and media like The Times , Pravda, NBC News, and The Washington Times, to name a few.


Basically, Lukas Pezawas' research focuses on the idea that genes affect the risk of developing mental illness. This idea is commonly-accepted, but how it works in detail, how genes might increase the brain's vulnerability for mental illnesses, is still a research area with many unanswered questions. In its June edition, Nature Neuroscience reported extensively on Pezawas' research study and the use of imaging genomics to uncover alterations in brain structure and function which are related to the genetic risk for psychiatric disorders like depression or anxiety. According to the article, combining functional imaging with genomics holds considerable promise for identifying the neural underpinnings of human individuality and for understanding how this variability interacts with the environment to produce both adaptive emotional behavior and disease states.

Imaging the human brain as an orchestra

To explain the study and its results to those who are not trained in brain research, Lukas Pezawas likes to compare the human brain's regulation of emotions to a well-tuned orchestra: The gene they found sounds a discordant note, increasing some people's susceptibility to anxiety and depression. This gene variant weakens a circuit in the brain used for processing negative emotions such as anxiety and depression. The study shows that a fear-processing hub deep in the brain, the amygdala, and an emotion-dampening center located near the front of the brain, the cingulum, were "playing a duet under the baton of the depression-linked gene," Pezawas explains.


The research team scanned 114 healthy subjects using magnetic resonance imaging (MRI). Those subjects with at least one copy of the variant had less grey matter - neurons and their connections - in the circuit in question than did subjects with a two normal genetic copies of the gene. How well this circuit was connected accounted for almost 30 percent of the test subjects' anxious temperament.

Depression - a common disease in the western world

According to the World Health Organization (WHO), depression is becoming one of the most common diseases. Mental disorders figure among the leading causes of disease and disability in Europe and beyond. In the WHO European Region, for example, 33.4 million people per year have been estimated to suffer from severe depression (58 out of 1000 adults). Globally, depressive disorders are currently the fourth leading cause of disease and disability, and are expected to rank second by 2020. In the long term, mental disorders can become a problem for the economy of a country, causing absence from work and costing society increasing amounts in sickness benefits and lost working days. "Unfortunately, governments don't yet recognize the whole danger and the consequences of mental disorders to the society, although the WHO recognized mental illness as one of the few leading medical problems with an incredible impact on socio-economic factors" Pezawas explains. "Compared to research funding in the classical fields of medicine like internal medicine, for example, funding for research on mental disorders in Austria is still negligible."


But although the funding opportunities for Pezawas' research are worse than in the US, and even his basic salary at the Medical University of Vienna is far less than he earned at the NIH, he decided to return to Vienna. "I came back because of the high quality of life in Vienna, not because of the conditions for research here - if that had been my top priority, I'd still be at NIH." This May, Pezawas submitted his postdoctoral lecture qualification and, in addition to his daily work schedule, is currently founding an "Imaging Genetics" group with colleagues at the MUV. "We do have the knowledge and also the necessary instruments to build a working group here in Vienna similar to the one I was working with at NIMH. All we need are some computers and some network-hardware, and of course the necessary human resources. As soon as we have solved this challenge, we can start with the real research," Lukas Pezawas adds, laughing.


- WHO, press release on depression
- Nature Neuroscience 8, no. 6, (2005): 701.
- Dr. Lukas Pezawas' website

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