Basic Science Research on Bipolar Disorder
Ranga N. Parthasarathy. Ph.D. and Rif El-Mallakh, M.D. - Principal Investigators
The Molecular Neuroscience and Bioinformatics Laboratories at the University of Louisville are under the direction of Ranga N. Parthasarathy. Ph.D. [link] This group, which includes Dr. Ratnam Seelan and Dr. Jagan Lakshmanan [links], has focused on molecular mechanisms of mood-stabilizing medications and antidepressants. They have performed a series of federally funded investigations of brain inositol signal enzymes modulated by antidepressants and have discovered a previously unrecognized signaling mechanism.
Dr. Parthasarathy’s research team has identified several gene candidates that may be modulated by lithium and other medications used for mood disorders. These findings have considerable potential for helping to understand the basic methods by which mood stabilizing medications work and to promote development of more effective treatments. Long-term goals of the Molecular Neuroscience Laboratory include human studies to determine if patients with depression and bipolar disorder have a mutation or DNA polymorphisms in inositol signaling genes, and also if these genes are potential markers for subtypes of depression.
Another research group directed by Rif El-Mallakh, M.D. has shown that a newly recognized stress hormone (known as ouabain-like compound) is dysregulated in bipolar disorder and that patients with bipolar disorder are less able to maintain extensive exercise than people without the illness. These researchers have also developed an animal model for mania that is being used extensively in bipolar research around the world. Dr. El-Mallakh’s group is currently working to understand a process called apoptosis (loss of brain cells) which appears to be a common finding in bipolar disorder. Because mood stabilizer medications appear to protect nerve cells from apoptosis, there is an important research opportunity to uncover methods of maintaining or enhancing healthy brain cell functioning.