Research Sheds Light on Treating Depression, Anxiety

Basic research in medicine analyzes the fundamentals of diseases and treatments. It requires the use of animals to understand how a living organism works when healthy and what goes wrong when disease strikes. Basic research with monkeys – hereby referred to as nonhuman primates – helps scientists understand and develop better treatments for psychiatric disorders including anxiety and depression.

Anxiety is the most common mental illness in America, affecting 40 million adults, which represents about 18% of the U.S. population.[1] More than 17 million adults in the U.S. suffer from depression.[2] A medical device treatment called deep brain stimulation (DBS) can reduce severe depression and anxiety in patients who do not respond to conventional therapies including drugs.

“Deep brain stimulation (DBS) was first developed as a treatment for Parkinson’s disease to reduce tremor[s], stiffness, walking problems and uncontrollable movements. In DBS, a pair of electrodes is implanted in the brain and controlled by a generator that is implanted in the chest,” according to the National Institute of Mental Health (NIMH). “Stimulation is continuous, and its frequency and level are customized to the individual.”

“Although it is unclear exactly how the device works to reduce depression or [obsessive-compulsive disorder (OCD)], scientists believe that the pulses help to ‘reset’ the area of the brain that is malfunctioning so that it works normally again,” the NIMH website said.

Deep brain stimulation, which requires brain surgery, is Food and Drug Administration approved for treating conditions including Parkinson’s disease and severe epilepsy as well as OCD. Researchers have successfully tested several different areas of the brain for treating depression with DBS, but more studies are needed to identify the best targets and to better understand how different approaches work. Non-invasive brain imaging and electroencephalogram (EEG) tests provide some information, but more detailed recordings and studies at the cellular and molecular level are also needed.

Studies using imaging have shown depression is associated with dysfunctional activity in a network of brain regions. DBS targets are generally in a subcortical or deep cortical location, which is where humans process more primitive functions such as emotion.

Doctors must carefully insert electrodes during a controlled medical procedure for both stimulation and recording purposes. These procedures inherently carry risks to the patient, which significantly limits scientists’ ability to learn on a broader scale.

An animal model with a brain anatomy similar to humans is essential for understanding brain network changes that help with symptoms of depression as well as with clinical recovery of patients with DBS operating in different areas of the brain.

Nonhuman primates are critical for such studies, according to research published in the Proceedings of the National Academy of Sciences of the United States of America.

Unlike rats and mice, nonhuman primates such as the Old World macaque monkey and the New World marmoset monkey have a prefrontal cortex like humans. They also have a cingulate cortex that looks and works the same way as in humans, unlike other animal models. Continued research with nonhuman primates will enable scientists to map out areas of the complex interaction of brain networks to better understand the causes and treatments of depression and anxiety disorders. This research will help determine how DBS impacts dysfunction of these networks at macro, micro and cellular levels, complementing and going beyond the more limited clinical studies possible in implanted human patients.

Treatment options for individuals with chronic depression and anxiety who do not experience adequate relief from their depression and anxiety are severely limited, but today’s studies provide hope for the development of new treatments.

Emerging therapies such as deep brain stimulation for depression show great promise, and research with nonhuman primates is an important key to unlocking their potential.

This article is based on: From bed to bench side: Reverse translation to optimize neuromodulation for mood disorders. Peter H Rudebeck, Erin L Rich, Helen S Mayberg. Proceedings of the National Academy of Sciences USA. 2019 Dec 23;116(52):26288-26296.

Scientific guidance of this article was provided by Robert H. Wurtz, PhD, distinguished investigator emeritus at the NIH’s National Eye Institute. Dr. Wurtz has served as president of the Society for Neuroscience and has been elected to the National Academy of Sciences, National Academy of Medicine, and American Academy of Arts and Sciences.

This article was vetted by Helen S. Mayberg, MD, professor of neurosurgery, neurology, neuroscience and psychiatry at the Icahn School of Medicine at Mount Sinai. She is the founding director of The Nash Family Center for Advanced Circuit Therapeutics in the Mount Sinai Health System.

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[1] https://adaa.org/understanding-anxiety/facts-statistics

[2] https://adaa.org/understanding-anxiety/depression