Breakthrough Research from HDRF,
September 5, 2018

What is Acetyl-L-Carnitine? Depression linked to low levels of brain molecule

A major study funded by Hope for Depression Research Foundation (HDRF) at Rockefeller University has revealed that a compound known as Acetyl-L-Carnitine (LAC) may be a biomarker for depression — a discovery that could lead to a potential blood test for depression.

The study, published July 30 in Proceedings of the National Academy of Sciences (PNAS), also points to a breakthrough new class of anti-depressant that is faster-acting and free of side effects than the current treatments that have been in use for the past 30 years.

The paper reveals that in both animal (rodent) studies and human pilot clinical trials, low LAC levels are linked to depression. People with particularly severe or childhood onset depression were found to have the lowest levels. The control subjects with no depression had normal levels of LAC. This suggests that in the near future, a blood test measuring LAC levels can diagnose depression severity.

Furthermore, in the animal studies, oral or intravenous administration of LAC actually reversed depressive symptoms and restored normal behavior within a few days.

The senior author of the paper is HDRF Depression Task Force member Dr. Bruce McEwen, head of the Laboratory of Neuroendocrinology at Rockefeller University. The lead author is Carla Nasca, PhD, a postdoctoral scholar in McEwen’s lab. Their extensive animal research was funded by HDRF.

“The findings … are clinically impactful and groundbreaking,” said Dr. Robert M. Post of the Department of Psychiatry at George Washington School of Medicine, in a written commentary in PNAS. “They hold the possibility of a new era of biological markers, personalized medicine, and paradigm-shifting acute and preventative treatments at the level of epigenetics.”

“Depression is the Number One reason for disability worldwide and the leading cause of suicide,” said Dr. McEwen. “But current pharmacological treatments are effective for only about 50 percent of the people for whom they’re prescribed. And they have numerous side effects, leading to long term non-compliance.”

Acetyl-L-Carnitine is a natural compound found in the body that aids in fat metabolism and energy production. Dr. McEwen’s studies show that the compound actually works on the genetic level, stimulating genes to produce a molecule that prevents excessive firing of nerve cells in key mood areas.

These results have far-reaching medical ramifications: clinicians are in dire need of a physical method to diagnose depression in adults as well as children, especially those who have lived through traumatic early experience. Currently the diagnosis of depression is very subjective; patients must self-report their symptoms to a doctor. At-risk children may not display depression symptoms until later in life, so a concrete method to identify depression early can lead to effective prevention.

While LAC is an exciting potential biomarker for depression, McEwen stressed that more research is necessary.

“It is likely that other biomarkers will be needed to further identify, or narrow down, to create a more specific depression subtype,” said Dr. McEwen. “That is, a combination of biomarkers may be needed rather than one alone.”

McEwen added: “Hopefully within the next year or two there will be additional information that may lead to a test.”

Dr. McEwen’s study represents one of the first efforts to achieve a precision medicine approach that treats the sub-types of depression, a major goal of the Depression Task Force since it was created in 2010. The Depression Task Force is a team of seven world leaders in brain science from different research institutions who are pooling expertise and data to accelerate discovery. They are conducting the most advanced depression research in the country today.

Here is a round-up of recent news on the breakthrough study:
ABC News
Science Alert
USA Today
Big Think

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