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May 20, 2015
Digest

Ketamine Lifts Depression via a Byproduct of Its Metabolism

A chemical byproduct, or metabolite, created as the body breaks down ketamine likely holds the secret to its rapid antidepressant action, NIH scientists and grantees have discovered. This metabolite singularly reversed depression-like behaviors in mice without triggering any of the anesthetic, dissociative or addictive side effects associated with ketamine.

The metabolite
singularly reversed
depression-like
behaviors in mice
without triggering
any of the anesthetic,
dissociative or
addictive side effects
associated with
ketamine.
The metabolite singularly reversed depression-like behaviors in mice without triggering any of the anesthetic, dissociative or addictive side effects associated with ketamine.

“This discovery fundamentally changes our understanding of how this rapid antidepressant mechanism works and holds promise for development of more robust and safer treatments,” said NIMH’s Dr. Carlos Zarate, a study co-author and a pioneer of research using ketamine to treat depression. “By using a team approach, researchers were able to reverse-engineer ketamine’s workings from the clinic to the lab to pinpoint what makes it so unique.”

NIMH grantee Dr. Todd Gould of the University of Maryland School of Medicine, in collaboration with Zarate and other colleagues, reported on the findings May 4 in Nature. The team also included researchers at NCATS, NIA and the University of North Carolina.

“Now that we know that ketamine’s antidepressant actions in mice are due to a metabolite, not ketamine itself, the next steps are to confirm that it works similarly in humans and determine if it can lead to improved therapeutics for patients,” explained Gould.

Clinical trials by Zarate and others have shown that ketamine can lift depression in hours, or even minutes—much faster than the most commonly used antidepressant medications now available, which often require weeks to take effect. Further, the antidepressant effects of a single dose can last for a week or longer. However, despite legitimate medical uses, ketamine also has dissociative, euphoric and addictive properties, making it a potential drug of abuse and limiting its usefulness as a depression medication.

NIH Creates Atlas of Human Malformation Syndromes

The Atlas of Human Malformation Syndromes in Diverse Populations is online at http://research. nhgri.nih.gov/atlas/.
The Atlas of Human Malformation Syndromes in Diverse Populations is online at http://research. nhgri.nih.gov/atlas/.

Researchers with NHGRI have collaborated with physicians and medical geneticists around the world to create the Atlas of Human Malformation Syndromes in Diverse Populations. Health care providers can use the new atlas to diagnose diverse patients with inherited diseases by comparing physical traits (called phenotypes) and written descriptions of their symptoms with photos and descriptions of people with the same condition and ancestry. Previously, the only available diagnostic atlas featured photos of patients with northern European ancestry, which often does not represent the characteristics of these diseases in patients from other parts of the world. The free electronic atlas was announced online in Genetics in Medicine.

“This atlas is long overdue and much needed,” said Dr. Daniel Kastner, NHGRI scientific director. “The impact of such a resource will be immediate and profound for all health care providers who are diagnosing and treating birth defects and genetic diseases in people of diverse ancestry.”

Congenital malformations, also known as birth defects, are the leading cause of infant deaths and diseases worldwide. Examples include heart defects, such as missing or misshaped valves; abnormal limbs, such as a clubfoot; neural tube defects, such as spina bifida; and problems related to the growth and development of the brain and spinal cord. Birth defects can be caused by genes not working properly, missing or extra chromosomes or mothers’ exposure to medications and chemicals during pregnancy.

Rapid-Response Immune Cells Are Fully Prepared Before Invasion Strikes

Through the use of powerful genomic techniques, researchers at NIAMS have found that the development of immune cells, called innate lymphoid cells (ILCs), gradually prepares these cells for rapid response to infection. This work, which appeared online May 5 in Cell, sheds light on the development and function of a cell type that is increasingly recognized as having an important role in the body’s immune defense.

“Up until now, researchers have focused on T cells—another type of immune cell,” said NIAMS scientific director Dr. John O’Shea, senior author of the paper. “ILCs are coming into the spotlight because they appear to have a critical role in defending the body’s barrier regions, such as the skin, lungs and gut, where microbes must first pass to make their way into the body.”

Our immune system has two arms—innate and adaptive. ILCs are innate immune cells that respond quickly against pathogens at the first site of invasion. They release small molecules called cytokines that transmit signals to fight infection.

Elevated Bladder Cancer Risk Tied to Arsenic in Water from Private Wells

Drinking water from
private wells may
have contributed
to the elevated risk
of bladder cancer
observed in Maine,
New Hampshire and
Vermont.
Drinking water from private wells may have contributed to the elevated risk of bladder cancer observed in Maine, New Hampshire and Vermont.

A new study has found that drinking water from private wells, particularly dug wells established during the first half of the 20th century, may have contributed to the elevated risk of bladder cancer that has been observed in Maine, New Hampshire and Vermont for more than 50 years. Other risk factors for bladder cancer, such as smoking and occupational exposures, did not explain the excess risk in this region. The study—by researchers at NCI and colleagues at Geisel School of Medicine at Dartmouth; the departments of health for Maine, New Hampshire and Vermont; and the U.S. Geological Survey—appeared May 2 in the Journal of the National Cancer Institute.

Bladder cancer mortality rates have been elevated in northern New England for more than half a century. The incidence of bladder cancer in Maine, New Hampshire and Vermont has been about 20 percent higher than that in the United States overall. Rates are elevated among both men and women. A unique feature of this region is the high proportion of the population using private wells for their drinking water, which are not maintained by municipalities and are not subject to federal regulations. These wells may contain arsenic, generally at low to moderate levels. Previous studies have shown that consumption of water containing high concentrations of arsenic increases the risk of bladder cancer.

There are two possible sources of arsenic in the well water in northern New England. Arsenic can occur naturally, releasing from rock deep in the Earth, and arsenic-based pesticides that were used extensively on crops such as blueberries, apples and potatoes in the 1920s through the 1950s.

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