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Creative Minds: Making Sense of Stress and the Brain

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Photo of a woman in front of a chalk board

Amy Arnsten
Credit: Terry Dagradi, Yale School of Medicine

Right behind your forehead lies the most recently evolved region of the human brain: the prefrontal cortex (PFC). It’s a major control center for abstract thinking, thought analysis, working memory, planning, decision making, regulating emotions, and many of the things we most strongly associate with being human. But in times of stress, the PFC is literally taken offline, allowing more primitive parts of the brain to take over.

Amy Arnsten, a neuroscientist at the Yale School of Medicine, New Haven, CT, has pioneered the study of stress on the brain [1] and how impaired regulation of stress response in the PFC contributes to neurological disorders, such as Attention Deficit Hyperactivity Disorder (ADHD), schizophrenia [2, 3], and Alzheimer’s disease [4]. In these disorders, cells in the PFC are negatively affected, while those in the primary sensory cortex, a more primitive part of the brain that processes vision and sound, are thought to remain relatively unscathed. With support from a 2013 NIH Director’s Pioneer Award, Arnsten hopes to uncover why the PFC is more vulnerable to disease than the primary sensory cortex—and how we might be able to prevent or reverse damage to these circuits.


Exploring the Complex Genetics of Schizophrenia

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Illustration of a human head showing a brain and DNA

Credit: Jonathan Bailey, National Human Genome Research Institute, NIH

Schizophrenia is one of the most prevalent, tragic, and frustrating of all human illnesses, affecting about 1% of the human population, or 2.4 million Americans [1]. Decades of research have failed to provide a clear cause in most cases, but family clustering has suggested that inheritance must play some role. Over the last five years, multiple research projects known as genome-wide association studies (GWAS) have identified dozens of common variations in the human genome associated with increased risk of schizophrenia [2]. However, the individual effects of these variants are weak, and it’s often not been clear which genes were actually affected by the variations. Now, advances in DNA sequencing technology have made it possible to move beyond these association studies to study the actual DNA sequence of the protein-coding region of the entire genome for thousands of individuals with schizophrenia. Reports just published have revealed a complex constellation of rare mutations that point to specific genes—at least in certain cases.


Charting the Chemical Choreography of Brain Development

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Drawing of baby, adolescent, and adult with decorative brains

Credit: Image courtesy of Scot Nicholls

Once in a while a research publication reveals an entirely new perspective on a fundamental issue in biology or medicine. Today’s blog is about such a paper. The story, though complex, is very significant.

The choreography of human brain development is amazing, but quite mysterious. Today’s post highlights a study [1] that reveals the locations of some of the chemical choreographers that collaborate with DNA to orchestrate these fancy moves in the brain.


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