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September 15, 2009

Yale study increases understanding of bipolar disorder

Damage to the brain caused by chronic stress or lead poisoning can be repaired by blocking a key molecular pathway, Yale University researchers report in the September 7-11 edition of the Proceedings of the National Academy of Sciences.

Rats subjected to chronic stress develop damage to the prefrontal cortex, an area of the brain crucial to working memory, impulse control and the ability to stay focused on tasks. Long-term stress triggers excessive activity of a family of enzymes called protein kinase C, which in turn damages the cytoskeleton of neurons and hinders their ability transmit information. This loss of the brain's grey matter due to stress has been linked to poor impulse control, a decline in working memory and inability to focus on tasks.

These findings have direct relevance to our understanding of bipolar disorder, where genetic insults increase protein kinase C signaling which may be associated with a loss of prefrontal grey matter and behavioral control.

The Yale team led by senior author Amy Arnsten, professor of neurobiology at Yale and her graduate student, Avis Brennan Hains, succeeded in protecting against the effects of stress by blocking the action of protein kinase C in rats. The researchers found that dendritic spines of neurons stayed intact and that the rats' ability to perform a task requiring working memory and impulse control was improved.

"When you inhibit protein kinase C, cells can talk to each other again and you rescue cognition," Arnsten said.

Blocking protein kinase C has potential for treating bipolar disorder and post-traumatic stress disorder, Arnsten said. Medications such as lithium can inhibit protein kinase C and have been shown to restore normal levels of grey matter in patients with bipolar disorder. She also noted such a therapy might help reverse the effects of lead poisoning, which causes learning disabilities and behavioral problems in tens of thousands of children. Lead, like stress, can also increase protein kinase C activity and erode grey matter in the prefrontal cortex. These findings suggest that medications that inhibit protein kinase C may help restore prefrontal brain function in children with residual problems from lead poisoning.

The study was funded by the National Institutes of Health and the Yale Stress Center.

We will analyze this research and post our findings on this blog.

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