Project Summary

Terence Ketter, M.D. (Independent Investigator 2003) of Stanford University, will seek to enhance understanding of the role of gamma-aminobutyric acid (GABA, a brain chemical that decreases nerve cell excitability) in bipolar II depression, and in the mechanism of action of the GABA-enhancing mood stabilizer valproate. Previously, he found that bipolar II depressed patients who had never had a mood stabilizer had about a 60% response rate, with an even higher (about 80%) rate in the those who had never had any psychiatric medication, but a lower (about 40%) response rate in those who had had prior treatment with antidepressants or stimulants. He also found decreased brain activity (reflected by decreased sugar usage) in a region near the front of the brain considered important in emotion called the anterior cingulate/medial frontal gyrus (AC/MFG) at baseline in bipolar depression patients who later responded to valproate compared to nonresponders. Also, recovered bipolar patients on valproate had AG/MFG GABA about 50% higher than healthy controls. This suggests that bipolar depressed patients able to respond to valproate compared to nonresponders could have relatively less compromised (that is, higher) AC/MFG GABA (reflected by relatively lower brain activity as GABA decreases nerve cell excitability) that is able to rise to above-normal levels with response to valproate. Using different brain imaging methods to measure AC/MFG GABA and brain activity before and after valproate therapy, and comparing pre- and post-treatment AC/MFG GABA and activity in responders and nonresponders, he will test his hypothesis that: higher (less compromised) baseline brain GABA is a marker of antidepressant response to valproate; Valproate's ability to increase GABA in nerve cells is also evident at the level of the human brain in valproate responders; GABA's association with decreased nerve cell activity is also evident at the level of the human brain; and lower baseline brain activity is a marker of antidepressant response to valproate (a replication of our earlier finding). Data obtained from this study may enhance knowledge of the role of GABA in bipolar II depression and valproate's mechanism of action, and could aid in targeting treatment in patients with bipolar disorders.

Program Area: MOOD DISORDERS\Bipolar

Search Again