Study provides link between stress levels, mental illness



Conventional wisdom that stress can cause a person to forget now has some scientific backing. Researchers, including some from Yale, found a link between stress levels and short-term memory associated with the enzyme protein kinase C. The findings, published in the Oct. 29 issue of Science, could also influence treatment of schizophrenia and bipolar disorder.

The researchers had known before the study began that stress interferes with working memory, which is activated during memory retrieval and depends on the prefrontal cortex.

“Exposure to uncontrollable stress, even a quite mild stress, can activate PKC in the prefrontal cortex,” said Amy Arnsten, professor of neurobiology at the Yale School of Medicine and the paper’s senior author.

High levels of stress, such as that experienced during an exam, can impair the prefrontal cortex and working memory. However, the study analyzed what happens inside cells during stress, said Shari Birnbaum GRD ’02, the paper’s first author and a post-doctoral research fellow at the Baylor College of Medicine.

“If we block PKC activity, we block the impairment due to stress,” Birnbaum said. “If we directly activate PKC, we impair working memory similar to what we see with stress.”

The PKC findings also have an impact on the understanding of schizophrenia and bipolar disorder. Arnsten said PKC is probably overactive in the brains of patients suffering from schizophrenia and bipolar disorder, both are associated with a prefrontal cortex impairment. She said this explains how stress could trigger the symptoms of both schizophrenia and bipolar disorder.

Changes in the levels of PKC in the prefrontal cortex affects brain function in that area. The enzyme regulates neuron excitability and the amount of neurotransmitter released, said Dr. Husseini Manji, director of the Laboratory of Molecular Pathophysiology at the National Institutes of Mental Health and a co-author on the paper.

“There is a fine range at which things like memory work efficiently,” Manji said. “If you slow it down or over activate it, the neuron fires more haphazardly — causing many higher cognitive functions to not work well.”

He said both schizophrenia and bipolar disorder are common mental illnesses — schizophrenia is found in about 1 percent of the population while bipolar disorder is found in about 1.5 percent of the population. Manji said both disorders tend to arise in the late teens and early 20s.

The research provides the possibility for new treatments directly targeting PKC.

“The hope is we could find medications more directly targeted at PKC, which would be more effective, have fewer side effects and act faster than current medications,” Birnbaum said.

Arnsten said drugs currently used to treat the disorders act outside the cell and can take several weeks to work, but new drugs targeting PKC could work more rapidly.

Comments