Monday, August 25, 2008

Brain structure examined in mood disorder research

From APA online - psychology in the news.

Brain structure examined in mood disorder research

- August 21, 2008

Aug. 21--NEW HAVEN -- The size of a small part of the brain that apparently plays a big role in memory and mood disorders is influenced by variations in a blood-vessel gene, Yale researchers have found, suggesting new ways to understand and treat depression, bipolar disorder and other mental illnesses.

The finding, published online by the journal Biological Psychiatry, builds on years of research at the Yale School of Medicine on the connections between mood, genetics and activity in the brain.

Specifically, the scientists have focused on the hippocampus, a structure at the base of the brain involved in memory, learning, emotions and Alzheimer's disease.

Previous research revealed that the hippocampus is smaller in depressed people, and that antidepressants enlarge the brain structure, possibly through a growth factor called brain derived neurotrophic factor (BDNF).

The discovery by Dr. Ronald Duman, a professor of psychiatry and pharmacology at Yale, seemed reasonable because BDNF is known to act in the brain and is involved with neural regeneration.

The latest research, based on brain scans and genetic analysis of 47 volunteers, suggests that another growth factor, vascular endothelial growth factor (VEGF), is also linked to the volume of the hippocampus.

Furthermore, scientists found that the stature of the hippocampus is significantly related to genetic variation in the subjects' VEGF genes.

Researchers, led by Dr. Hilary P. Blumberg, director of Yale's Mood Disorders Research Program, said the finding that implicated VEGF in hippocampal size suggests that VEGF is "important to the hippocampus structure in humans." This, in turn, may mean that depression, bipolar disorder and other ailments might be treatable through the VEGF pathway, Blumberg said.

VEGF, which controls the growth of blood vessels, has been examined extensively by oncologists searching for a way to starve malignant tumors. It is also of interest to researchers looking for treatments for macular degeneration, which involves uncontrolled growth of vessels over the retina.

A variety of growth factors may affect the parts of the brain that underlie the symptoms in mood and other neuropsychiatric disorders, she said. Likewise, multiple genes may be responsible for mental illnesses.

Different genes may account for the diversity of symptoms in a disorder such as depression, which is marked by insomnia and sleeping too much, over-eating or loss of appetite, and other extremes.

How the variation in the VEGF gene affects the hippocampus in not clear, Blumberg said. She suggests that it is linked to the discovery last year by Duman that, in addition to its role in stimulating vascular growth, VEGF is an essential mediator in the growth of new nerve cells.

Dr. Joel Gelernter, professor of psychiatry at Yale, was also examining genetic variations in VEGF in humans.

Consequently, Blumberg, Duman, Gelernter and colleagues conducted DNA tests (and brain scanning of) 47 healthy men and women to assess how differences in VEGF genes might influence the structure of the brain.

They found that different versions of the VEGF genes were associated with the volume of the hippocampus.

New directions for our research will be to study how genetic variations, like those in VEGF, may contribute to the differences in brain circuitry that underlie mood disorders, Blumberg said.

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