Renshaw awarded grant to research new treatment for major depression

Studies may give hope to teen girls with treatment-resistant major depressive disorder (MDD)

2012-3-26 - Perry Renshaw, M.B.A., M.D., Ph.D., USTAR professor of psychiatry, was awarded $450,000 from the National Institutes of Health (NIH) to investigate whether the dietary supplement creatine may benefit teen girls with treatment-resistant depression. Douglas Kondo, M.D., USTAR assistant professor of psychiatry, and Young-Hoon Sung, research assistant professor of psychiatry, will be co-investigators on the project.

Those with major depressive disorder (MDD), or clinical depression, feel a loss of interest or pleasure in normally enjoyable activities, adversely impacting work or school, health, and family. Perhaps surprisingly, between 15-25% of teens in the U.S. experience depression, prompting some experts to call it America’s “hidden epidemic.” During adolescence, the rate of MDD in females doubles, remaining twice that of males throughout womens reproductive years. Therefore, successful early intervention for MDD must be able to successfully treat adolescent females.

“From a global perspective, depression is the world's number one illness burden on females between 15 and 45 years old,” said Kondo. “Our goal is to reduce the negative impact of depression on the many adolescent females who don't respond to currently available treatments.”

The most common treatment for MDD is a class of antidepressants called selective serotonin reuptake inhibitors (SSRIs). However, some studies suggest that SSRIs are ineffective in treating up to half of patients with mood disorders. What’s more, many patients cease taking SSRIs because of unpleasant side effects. These facts obviate the need for better treatment options for MDD.

Renshaw’s team will investigate whether creatine supplements – frequently taken by athletes to improve muscle performance – may benefit adolescents with treatment-resistant MDD. Produced naturally by the body, creatine fuels a metabolic pathway that generates energy within muscle and brain cells. This extra boost may help brain cells to better perform basic neurological functions involved in mood regulation.

To determine the physiological effects of creatine on the brain, they will use 31-Phosphorus Magnetic Resonance Spectroscopic Imaging (31P-MRSI), a safe and non-invasive imaging method, to measure concentrations of high-energy cerebral metabolites. For these studies they will measure beta-nucleoside triphosphate (b-NTP; largely adenosine triphosphate, or ATP) and phosphocreatine (PCr).

Renshaw’s group has shown that in healthy adults, dietary supplementation with creatine increases total brain creatine, and induces alterations in PCr and b-NTP that are associated with an increased likelihood of response to both antidepressants in treatment-naïve MDD, and thyroid hormone augmentation in treatment-resistant MDD. Based on these findings, they will investigate whether creatine also promotes a treatment-responsive state in teen girls with MDD. The long-term goal of this research is to delineate the alterations in brain chemistry energy metabolism that are associated with mood disorders, and to identify treatment improvements.

“Depression in women is linked to several major medical illnesses,” said Kondo. “A novel intervention for adolescent females with MDD has the potential to broadly impact public health, beyond the boundaries of psychiatry.”

Douglas Kondo, M.D. is recruiting female adolescents between the ages of 13-18 who have depression to participate in the study.
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Last Updated: 3/14/13