Faculty Innovators

Amy Arnsten

Repairing the ‘Fabric of Thought’ with Drugs To De-Stress the Brain

As Amy Arnsten puts it, the prefrontal cortex is the Goldilocks of the brain: “It needs everything just right.”

When working properly, this most evolved part of the brain allows people to plan ahead, make complex decisions, organize and multi-task.

But under stress, the prefrontal cortex can malfunction — as chemicals are unleashed, stopping cells from communicating properly and hampering the cells from regulating thought and behavior.

Arnsten has devoted much of her work to developing medications that allow the brain cells in the prefrontal cortex to talk with each other more easily, thereby reducing or preventing the effects of stress or harmful genetic alterations.

In recent years, she made key discoveries of substances for treatment of mental disorders involving this area of the brain.

Shire Pharmaceuticals is developing Arnsten’s discovery of the use of guanfacine for treatment of attention-deficit hyperactivity disorder (commonly known as ADHD) and other similar disorders. The FDA has ruled Shire’s New Drug Application “approvable,” and the compound is undergoing final safety testing.

Yale’s Office of Cooperative Research is working with Arnsten to find a company to develop her discovery of the use of chelerythrine for treatment of schizophrenia, bipolar disorder, post-traumatic stress disorder and other related conditions.

A professor of neurobiology and psychology, Arnsten credits a pivotal moment while she was still studying neuroscience in college with putting her on her path to discovery.

It was summer, and she volunteered in her home state of New Jersey in a mental hospital that housed thousands of patients. Medications available then were inadequate, and Arnsten saw a need for neuroscientific insights into crippling mental illnesses. There were only two psychiatrists on staff, one with a penchant for administering painful electro-convulsive therapy — which today is still used to treat severe depression but has been improved so as to be painless.

One day back then, Arnsten was having a lucid conversation about astronomy with a patient who had been a physicist, when that doctor’s name came up. The comment triggered an immediate negative response: The man’s speech became disordered and incoherent, barely making sense.

“It was such a huge clue,” Arnsten said, “that stress can neuro-chemically alter the fabric of thought. It was a big clue in the treasure hunt that’s become my career.”