Fighting Depression: Ketamine Metabolite May Offer Benefits Without the Risks

Depressed Woman

Thinkstock/Ryan McVay

For people struggling with severe depression, antidepressants have the potential to provide much-needed relief, but they often take weeks to work. That’s why there is growing excitement about reports that the anesthetic drug ketamine, when delivered intravenously in very low doses, can lift depression and suicidal thoughts within a matter of hours. Still, there has been reluctance to consider ketamine for widespread treatment of depression because, even at low doses, it can produce very distressing side effects, such as dissociation—a sense of disconnection from one’s own thoughts, feelings, and sense of identity. Now, new findings suggest there may be a way to tap into ketamine’s depression-fighting benefits without the side effects.

In a mouse study published in the journal Nature, an NIH-funded research team found that the antidepressant effects of ketamine are produced not by the drug itself, but by one of its metabolites—a substance formed as the body breaks ketamine down. What’s more, the work demonstrates that this beneficial metabolite does not cause the risky dissociation effects associated with ketamine. While further development and subsequent clinical trials are needed, the findings are a promising step toward the development of a new generation of rapid-acting antidepressant drugs.

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LabTV: Curious About Fatigue Related to Cancer Therapy

Leorey Saligan

As this LabTV profile of an outstanding nurse-scientist shows, there are many different paths to a career in biomedical research. Leorey Saligan grew up in the Philippines, where the challenges and rewards of caring for sick family members inspired him to become a nurse. His first job was at a nursing home in Midland, TX, and the next at a nearby hospital. Later, Saligan moved to Norfolk, VA, where as a nurse practitioner he began caring for people with sarcoidosis, an inflammatory disease that affects several organ systems.

Saligan went on to pursue a Ph.D. in nursing at Virginia’s Hampton University, writing his dissertation on the chronic vision problems associated with sarcoidosis. To gather more data on such problems, he joined NIH’s National Institute of Nursing Research in Bethesda, MD, and, with the help of colleagues, carried out a clinical study. To Saligan’s surprise, the data showed that fatigue, rather than poor vision, was the top concern of people with sarcoidosis. That discovery sparked his research interest in fatigue—an interest now focused on the intense, often debilitating fatigue that many people with cancer experience both during and after treatment, particularly radiation therapy.

Like people with sarcoidosis, people undergoing cancer treatment report that fatigue is the symptom that most negatively affects their quality of life. Many find the fatigue so distressing that their treatment regimens have to be reduced or even halted—actions that may have a negative effect on the cancer-killing power of such treatments. And, for some folks, the fatigue can be long lasting, persisting for months or even years after cancer therapy ends.

By analyzing blood and tissue samples donated by volunteers who are undergoing or who have undergone cancer treatments, Saligan and colleagues from NIH’s Clinical Center and National Cancer Institute have uncovered several promising leads in their effort to gain a better understanding of the molecular mechanisms of treatment-related fatigue. He is also working with behavioral researchers to explore the relationship of fatigue with pain, depression, anxiety, sleep disturbances, and other symptoms. Ultimately, this NIH tenure-track investigator (who also happens to be an officer in the U.S. Public Health Service) wants to see this scientific knowledge translated into effective ways of treating or preventing the fatigue that is a most unfortunate side effect of potentially life-saving cancer therapies.

Links:

LabTV

Leorey N. Saligan (National Institute of Nursing Research/NIH)

Investigating Molecular-Genetic Correlates of Fatigue Experienced by Cancer Patients Receiving Treatment (ClinicalTrials.gov/NIH)

Effect of Ketamine on Fatigue Following Cancer Therapy (ClinicalTrials.gov/NIH)

Science Careers (National Institute of General Medical Sciences/NIH)

Careers Blog (Office of Intramural Training/NIH)

Scientific Careers at NIH

 

Creative Minds: The Muscle-Brain Connection

Muscle activity and brain functionThere’s mounting evidence that exercise has a powerful effect on the human brain. For example, many studies have shown that physical activity appears to reduce the incidence of depression. Exercise can also delay or possibly even prevent Alzheimer’s disease, as well as easing symptoms in people who have these disorders [1, 2, 3, 4, 5]. But how, exactly, does getting our legs moving and our hearts pumping exert a positive influence on our brains?

Two scientists at Stanford University School of Medicine are out to get some answers to this important question. They have proposed that when we exercise, our muscles secrete a factor or combination of factors into the bloodstream, leading to structural and functional changes in the brain.

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Team Approach Helps Teen Depression

Team of Support

Stock photo

As many as one in five U.S. teenagers experience an episode of major depression by the time they turn 18. Sadly, depression among teens often goes unrecognized, increasing the risk of suicide, substance abuse, and many other problems. Even among those who are diagnosed, few receive proper treatment. But now there’s a ray of hope from a new NIH-funded study that’s found success using a team approach that pairs depressed teens and their parents with a counselor [1].

Faced with a shortage of psychiatrists who specialize in child mental health, a multidisciplinary team from the Seattle Children’s Research Institute, University of Washington School of Medicine, and Group Health in Seattle decided to use a strategy called “collaborative care” to treat depressed teenagers. There are more than 70 clinical trials showing that team-based care approaches work well for adults with depression, but there were only two such previous studies in teens—and results were mixed.

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Creative Minds: Can Microbes Influence Mental Health?

Photo of a young woman

Elaine Hsiao
Credit: NIH Common Fund

While sitting in microbiology class as a college sophomore, Elaine Hsiao was stunned to learn that the human gut held between as much as 6 pounds of bacteria—twice the weight of an adult human brain. She went on to learn during her graduate studies in neurobiology that these microbes had co-evolved with humans and played important roles in our bodies, aiding digestion and immune function, for example. But more intriguing to her, by far, was new research that suggested that gut bacteria might even be influencing our thoughts, moods, and behavior.

Now a senior research fellow at the California Institute of Technology, Hsiao is launching her own effort to explore how these microbes can affect brain function—a very creative endeavor made possible through NIH’s Early Independence Award program—also known as the “skip the postdoc” award.

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