Blood Vessel Gene Influences Brain Size, Yale Researchers Find

The size of a key area of the brain involved in memory and mood disorders is influenced by variation in a growth factor gene that influences blood vessel growth and has been widely studied in heart disease and cancer, Yale University researchers have found.

The magnetic resonance imaging brain scanning and genetics study, published online Tuesday in the journal Biological Psychiatry, is another piece of emerging evidence suggesting that vascular endothelial growth factor, or VEGF, may be crucial to mental health. And the variations in brain volume associated with the VEGF gene suggest a possible cause of cognitive symptoms reported by some patients using anti-VEGF therapies for cancer and other diseases.

“The combination of brain imaging and genetics research has exciting potential to reveal the genes that are important in the development of brain disorders. As we identify these genes, we can develop new and more effective treatments that could target the related, specific molecular mechanisms ” said Hilary Blumberg, MD, neuroimaging expert and lead author of the study. Dr Blumberg is an Associate Professor of Psychiatry, Diagnostic Radiology at the Yale School of Medicine and Yale Child Study Center as well as Director of Yale’s Mood Disorders Research Program.

VEGF promotes blood vessel growth - a process called angiogenesis. The growth factor has been a favorite target for scientists seeking to starve cancer tumors of their blood supply. Other scientists have been interested in activating VEGF to help repair damaged hearts. Now it appears that this growth factor may also be crucial for the development and repair of the hippocampus, an area of the brain where memory is consolidated and which has been implicated in mood disorders such as depression and in dementias such as Alzheimer’s disease.

Yale University researchers have been at the forefront of the hunt for genes that stimulate the growth of new neurons, a process called neurogenesis, in the hippocampus. The field was jumpstarted when Ronald Duman, Ph.D, Professor of Psychiatry and Pharmacology and Director of the Division of Molecular Psychiatry and Abraham Ribicoff Research Facilities, noted in 2000 that anti-depressants triggered the creation of new cells in the hippocampus.

Last year, Duman found that in addition to its role in stimulating blood vessel growth, VEGF is an essential mediator of neurogenesis of new brain cells. Joel Gelernter, MD, Professor of Psychiatry and Director of the Division of Human Genetics at the Veterans Affairs Medical Center, was also examining genetic variations in VEGF in humans. So Blumberg, Gelernter, Duman and colleagues extended the research to humans and did DNA tests on 47 healthy individuals to assess genetic variations in VEGF and conducted brain imaging scans of the subjects to examine how these genetic variations might influence the structure of the brain. They found that the volume of hippocampus was significantly related to variations in the VEGF gene in their subjects.

Other researchers on the paper are Dr. Fei Wang who is the co-leader of this study, Dr. Lara Chepenik, Dr. Jessica Kalmar and Erin Edmiston.

The research was supported by grants from the National Institute of Mental Health, Department of Veterans Affairs, National Alliance for Research on Schizophrenia and Depression, The Ethel F. Donaghue Women’s Investigator Program at Yale and the Klingenstein Foundation.

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