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McLean researchers Christian A. Webb, PhD, assistant neuroscientist in the Laboratory for Translational and Affective Neuroscience, and W. Brad Ruzicka, MD, PhD, assistant neuroscientist in the Mailman Research Center, are winners of the 25th annual Alfred Pope Award for Young Investigators, McLean’s highest research honor.
They each presented their research at a special Grand Rounds lecture on June 2, followed by a brief question and answer session. The award, which carries a $750 cash prize, recognizes the publication of an exceptional peer-reviewed, first-authored article on basic or clinical research performed at McLean.
Given annually to young researchers whose innovative work promises to make significant advancement in the understanding of psychiatric illness, the Pope Award honors one of the hospital’s most distinguished and respected researchers, the late Alfred Pope, MD, former director of McLean’s Ralph Lowell Laboratories.
“McLean is proud to have Drs. Webb and Ruzicka as members of our research community,” said McLean Chief Academic Officer Shelly F. Greenfield, MD, MPH. “Through their innovative approaches to studying mental illness, each have made important contributions in helping us better understand the underlying causes of the disease process.”
Webb’s presentation centered on his publication in the journal Neuropsychopharmacology, “Neural Correlates of Three Promising Endophenotypes of Depression: Evidence from the EMBARC Study,” for which he was selected to receive the award. His research focuses on clarifying the etiology and underlying pathophysiology of depression. In addition, he also conducts research aimed at improving scientists’ understanding of the psychosocial and neurobiological mechanisms that account for symptom improvement in treatments for depression, with a particular focus on cognitive behavioral approaches.
In discussing his article, Webb noted that “there are approximately 1,000 different permutations of symptoms that meet criteria for a diagnosis of major depressive disorder, and these often very different combinations of symptoms are implicitly assumed—at least in our current diagnostic system—to be interchangeable indicators of the same, one underlying disorder.
“There have been efforts in the field to try to make sense of and parse the vast heterogeneity in depressive symptoms,” he said. “One potentially fruitful approach to parsing this heterogeneity is to focus on promising endophenotypes of depression.”
“Endophenotypes are assumed to lie on the pathway between genes and disease, and be relatively less complex and more tractable than the downstream symptom clusters that currently define psychiatric diagnoses like depression. Our analyses indicated that depressed patients could be differentiated into several subgroups on the basis of their endophenotype profiles. This knowledge may ultimately help inform not only diagnostic subgrouping but also in selecting the optimal treatment for a given depressed individual based on their particular endophenotype profile,” he added.
Webb has received numerous awards for his work, including an Early Career Award from the American Psychological Association, a Child Intervention, Prevention, and Services Fellowship from the National Institute of Mental Health (NIMH), a NARSAD Young Investigator Award, and the Dissertation Award from the Association for Behavioral and Cognitive Therapies. He has also secured external funding for his research at the pre-doctoral, post-doctoral, and faculty levels.
W. Brad Ruzicka, MD, PhD, focused his speech on the results of his publication in the journal JAMA Psychiatry, “Circuit- and Diagnosis-Specific DNA Methylation Changes at GABA-Related Genes in Postmortem Human Hippocampus in Schizophrenia and Bipolar Disorder,” for which he was selected for the award.
Ruzicka’s paper reports a rigorous project at the cutting edge of clinical neuroscience, which has resulted in a significant contribution to the understanding of epigenomic mechanisms active in the pathophysiology of psychotic disorders. For this work, he deconstructed the circuitry of the hippocampus by using laser microdissection to sample tissue from distinct subregions of postmortem human hippocampus.
“Studying epigenetics—mechanisms that are specific cell to cell, as opposed to genetic mutation—offers the potential to explain how changes that happen in a psychotic illness can impact certain parts and circuits within the brain selectively,” said Ruzicka.
“The key finding of this study is that epigenetic changes are distinct between different circuits within the hippocampus in subjects with bipolar disorder or schizophrenia and healthy controls, and are not homogenous throughout the whole structure.”
He pointed out that when data is collected from studying homogenized brain tissue, “we’re disregarding a huge amount of information about which cell types and circuits are important to the disease process. This is vital information in understanding how these diseases manifest in the brain and how we can more effectively and more selectively target symptoms and try to develop treatments that have fewer side effects.”
Ruzicka has received other awards and grants for his work, including the Maria Lorenz Pope Fellowship from McLean, the Epigenetics Initiative Travel Grant from Harvard Medical School, and the Early Career Investigator Travel Award from the Society of Biological Psychiatry.
Kerry J. Ressler, MD, PhD, McLean’s chief scientific officer and chief of the Depression and Anxiety Disorders Division, said, “The breakthroughs in research that Drs. Webb and Ruzicka have pioneered in their areas of study will no doubt help scientists develop better treatments in depression and psychotic illness. With this new insight, the ultimate goal, of course, is to prevent these diseases from manifesting in those individuals who are at greatest risk.”