Dr. Hilary Blumberg, Assistant Professor of Psychiatry and Director of the Mood Disorders Research Program, has long been interested in the brain circuitry of individuals with mood disorders. After extensive research into both brain derived neurotrophic growth factor (bDNF) and vascular endothelial growth factor (VGEF), Blumberg is starting to find some answers.
Inspired by the research of Ronald Duman, Professor of Psychiatry and Pharmacology, that examined the effect of bDNF and VEGF on the growth of brain cells in animals, Blumberg was lead author of her own study that investigated the effect of both genes on the human brain.
Blumberg and her colleagues utilized three types of MRI in order to provide a comprehensive understanding of the human brain. A structural MRI provided the size, shape and volume of the brain, a functional MRI (fMRI) indicated brain and circuitry functions, and diffusion tensor imaging showed connections responsible for emotional processing.
The study showed that VEGF, which promotes angiogenesis – the growth of new blood vessels – is necessary for growth and repair of the hippocampus. The combination of the three imaging techniques indicated that the volume of the hippocampus was strongly correlated with the variation in VEGF genes, and that hippocampal volume was smaller in the brains of people with mood disorders than in normal brains.
Connections important for emotional processing were also smaller in adolescents and adults with mood disorders, and this difference was found to magnify over time. These findings helped establish the ages of vulnerability to mood disorders, stressing the importance of early intervention for treatment.
Blumberg believes that the connection between VEGF and the hippocampus development will allow mood disorders to be studied more clearly. Her findings will also enable closer study of the relationship between VEGF and other cognitive disorders.
The study also raises several interesting questions about the possible use of VEGF in other areas of medicine. VEGF inhibitors are already used in treatment of cancer and macular degeneration. It will be important to study the possible negative side effects of these treatments.
According to Blumberg, “This opens doors to say, ‘Should we be looking down this whole other set of mechanisms – and might they provide new treatment?’”
Still, it is important to note that both genetic and environmental influences contribute to mood disorders.
By studying the genetic factors, Blumberg and her colleagues hope to get at the basic mechanisms of mood disorders. This may potential allow doctors to intervene earlier and prevent the progression of the disorder.
The researchers also hope to be able to identify young children with genetic predispositions to mood disorders so that biological factors can be strengthened and external factors reduced, lowering the chances that susceptible children will in fact develop mood disorders.
While the link between the VEGF gene and hippocampal development is significant, Blumberg recognizes that much work remains to be done. In her words, “Everyone’s working closely together, and that’s how these discoveries get made. We have excellent collegiality and can work together to put together the pieces of the puzzle.”