Current Progress in Developing More Effective Treatments for Bipolar Disorder

Current Progress in Developing More Effective Treatments for Bipolar Disorder

Posted: March 1, 2013

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WOMEN’S MENTAL HEALTH CONFERENCE: THE ART & SCIENCE OF CARING

From The Quarterly, Winter 2013



On September 14, 2012 the Brain & Behavior Research Foundation hosted a Women’s Mental Health Conference: The Art & Science of Caring in New York City. The event included a panel discussion on Early Intervention, Rehabilitation and Reintegration; small group discussions with leading researchers across mental illnesses; and a final panel discussion on overcoming stigma and the future of public policy and research. The following pages contain highlights of some of the presentations. Full transcripts of the talks and a highlight video are available at bbrfoundation.org/2012-WMHC.



Current Progress in Developing More Effective Treatments for Bipolar Disorder

Wayne Drevets, M.D.

Brain & Behavior Research Foundation Scientific Council Member

1996 NARSAD Young Investigator Grantee

1999 NARSAD Independent Investigator Grantee

Vice President

Mood Disease Area Leader, Neuroscience Therapeutic Area

Janssen Research and Development



The goal of research by Dr. Drevets and his colleagues is to learn what current treatments for bipolar disorder actually do inside the brain, and how this information can lead to more effective treatments. He outlines some of the critical brain functions known to be impeded in bipolar disorder and explains how researchers are working to target these areas with new treatments.



Brain function is controlled by a process called neurotransmission through which nerve cells, or neurons, communicate via chemicals called neurotransmitters. The neurotransmitter glutamate, which controls glucose metabolism, is responsible for 80 percent of the brain’s neurotransmission. Too much glutamate transmission and a corresponding overproduction of glucose adversely affect neuron health and are critically involved in bipolar disorder.



The neurotransmitter sent by a signaling neuron is apprehended by molecules of structures, called dendrites, on the neuron receiving the message. Glucose overproduction destroys dendrites, leading to a reduction in brain tissue volume. Animal studies have shown that the areas affected by this abnormal neurotransmission are those associated with emotion regulation. Studies have also shown that some of the successful treatments for bipolar disorder, principally lithium, restore normal emotional function by restoring dendrite development.



Two proteins involved in dendritic restoration are brain-derived neurotrophic factor (BDNF) and Bcl-2. In bipolar disorder there is evidence of reduced BDNF, impeding the creation of new neurons. While lithium and valproic acid, another treatment for bipolar disorder, reverse this negative BDNF effect, these drugs do not restore functioning of Bcl-2. Dr. Drevets is exploring new drug developments to restore Bcl-2 function.



A significant finding of Dr. Drevets’ research has been the decrease of glial cells in patients with mood disorders. Glial cells are brain cells that support the functioning of neurons—and also take up excess glutamate. Dr. Drevets and colleagues found that glial decrease leads to dendritic decrease; he and his team are currently exploring ways to reverse loss of glial function.



Another avenue being explored by Dr. Drevets and many mood disorder researchers is the rapid-acting antidepressant effect of ketamine. Ketamine can induce antidepressant effects in a few hours, as opposed to the weeks needed for conventional antidepressants to work. The downside is that ketamine’s benefits last only a few days. A major line of research now underway is to discover how to prolong ketamine’s beneficial effects and to reduce the occurrence of any adverse side effects.