Archive for the ‘the journal Nature’ Tag

Ketamine — A New Drug Treatment For Depression?

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Credit: Koratmember at FreeDigitalPhotos.net

Remember ketamine, the old veterinary (and sometimes street) drug? Apparently it rapidly and significantly reduces anhedonia in those with treatment-resistant bipolar disorder, according to a new study.

Anhedonia, which is a lack of interest in activities that once gave a person pleasure, is a key feature of treatment-resistant bipolar disorder. According to a recent NIH-funded clinical trial, ketamine restored pleasure-seeking behavior independent of its other antidepressant properties in these patients. What’s more, it did so about 40 minutes after a single infusion, and the effect lasted as long as 14 days.

To me the most interesting part of this study is that ketamine did not act on the midbrain areas typically involved in depressive symptoms. Rather, PET scans on patients in the depressive phase of bipolar disorder showed that after ketamine infusion, there was activity in the dorsal anterior cingulate cortex (dACC). This region lies deep within the brain, resting on the medial surface of the frontal lobes. Its precise role remains somewhat elusive, though it is thought to govern conscious control of goal-directed behavior. The most recent significant study I could find on its function was a 2012 paper in Nature suggesting that the dACC is involved in optimizing behavioral adaptations to continuously evolving demands by predicting the difficulty of a task.

“Our findings help to deconstruct what has traditionally been lumped together as depression,” explained Carlos Zarate, M.D., of NIMH. “We break out a component that responds uniquely to a treatment that works through different brain systems than conventional antidepressants — and link that response to different circuitry than other depression symptoms.”

Imaging studies similar to the one just published are underway in patients with major depression, though results are not yet available. Other studies have suggested that ketamine may be exerting these effects through glutamate and dopamine pathways. Research is underway to explore easier methods of drug delivery, such as nasal spray.

Of late, ketamine has been studied for its rapid antidepressant properties, providing relief within hours rather than the weeks required for traditional medications to work. At present, ketamine is not FDA approved for treatment of depression and it is still used primarily in a veterinary setting.

Ketamine is an NMDA receptor antagonist, though it also inhibits reuptake of dopamine, serotonin, and norepinephrine. It was developed in 1962 and has been used in both humans and animals. It is categorized as a dissociative agent. It has been used for general anesthesia, sedation, and as a pain killer. Side effects include amnesia and agitation, and its street use has led to hallucinations, delirium, and death.

Scientists Explore Shared Biology In Human, Fly, and Worm Genomes

 

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Credit: rajcreationzs at FreeDigitalPhoto.net

Researchers analyzing human, fly, and worm genomes have found that these species have a number of key genomic processes in common, reflecting a shared ancestry. Three papers were published in the Aug. 28, 2014 issue of Nature offering insights into embryonic development, gene regulation, and other biological processes vital to understanding human biology and disease.

These studies utilized data generated by the model organism ENCyclopedia Of DNA Elements (modENCODE) and the ENCyclopedia Of DNA Elements (ENCODE) Project, both supported by NHGRI. Launched in 2007, the goal of modENCODE is to create a comprehensive catalog of functional elements in the fruit fly and roundworm genomes for use by the research community. Initial catalogs were published in 2010. The ENCODE Project is building a comprehensive catalog of functional elements in the human and mouse genome.

More than a dozen modENCODE Consortium papers have been or will be published in the journals Nature, Genome Research, Genome Biology, and the Proceedings of the National Academy of Sciences this year. This collection of papers is the culmination of the modENCODE program, for which funding ended in 2012. More than 100 papers using modENCODE data by groups outside of the program have already been published. It is anticipated that the data and resources produced by modENCODE will continue to be used by the broader research community for years to come.

NIH Funding to Study Sex as a Fundamental Variable in Clinical Research

Credit: Photokanok at FreeDigitalPhotos.net

Credit: Photokanok at FreeDigitalPhotos.net

I am popping up from my mountain of R01 drafts to bring attention to an important NIH news release. Yesterday, NIH announced it has devoted over $10 million in supplemental funding for 82 grantees to explore sex differences in their clinical and pre-clinical research.

The news release states, “These awards are the latest round of funding in a program described in a May 2014 Nature commentary by [Janine Austin Clayton, M.D., NIH associate director for women’s health research] and NIH Director Francis S. Collins, M.D., Ph.D. This commentary informed NIH grantees and other stakeholders of the agency’s intent to develop policies that will require applicants to address the influence of sex in the design and analysis of biomedical research with animals and cells.”

The news release states that the goal of the supplements is to serve as “…a catalyst for considering sex as a fundamental variable in research.”

NIH began this program in FY13, initially funding 50 supplements ($4.6 million total.) The initiative has been led by the Office of Research on Women’s Health. Most of the NIH ICs have funded supplements since the inception of the program.

Historically, medical research has been conducted predominantly on white male subjects. NIH has made efforts to expand the scope of clinical research to include both sexes and to represent multiple races and ethnicities. Grantees who want to succeed in the NIH arena would be wise to incorporate such variables into current and future studies.

 

 

Interview with Francis Collins about Biomedical Workforce Development Initiatives

On December 11, the NIH Office of the Director issued  a press release describing two main NIH initiatives: workforce development and data and informatics. (see links to the press release and original report here.) Last week Gene Russo published an interview with Francis Collins in the journal Nature in which he asked Dr. Collins to discuss in more detail the workforce development initiative. Dr. Collins states that “Only about 23% of US-trained biomedical PhD holders were in academic tenure or tenure-track positions in 2008,” which may help explain the avalanche of queries I receive about medical writing careers.

Summary from the Nature article:

For years, the US National Institutes of Health has struggled with promoting non-academic career tracks for biomedical scientists, gauging the supply of PhD holders and demand for research jobs, enticing under-represented minorities into science and establishing funding avenues for early-career researchers. Hoping to bring some evidence-based clarity to these issues, NIH director Francis Collins asked two working groups of the NIH Advisory Committee to study the issues and make recommendations. They released their recommendations in two reports in June; Collins responded in December. The NIH has decided to take measures that include raising its postdoc stipend, increasing the number of grants that encourage early-career independence and offering 25 institutional grants, each worth about US$250,000, to support training programmes that prepare students for a broad range of research-related careers, including non-academic paths.

Read the full interview here.

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