Foundation-Funded Study Leads to Important Discovery about Stress and Mental Illness

Foundation-Funded Study Leads to Important Discovery about Stress and Mental Illness

Posted: February 19, 2014

Story highlights


Researchers led by 2009 NARSAD Young Investigator Grantee Daniela Kaufer, Ph.D., of the University of California, Berkeley, have made a major new discovery that may explain how stress or trauma creates a biological vulnerability in the brain that can result in depression, post-traumatic stress disorder (PTSD), or several other disorders years after the stress was experienced.

This lag time between the occurrence of stress and the appearance of behavioral symptoms has been a great mystery in research. Dr. Kaufer and a team that included Robert Sapolsky, Ph.D., of Stanford University, recipient of a 2004 NARSAD Distinguished Investigator Grant, tested a hypothesis that challenged certain widely held beliefs about how the brain functions.

Thanks to pioneering research supported over the years with NARSAD Grants to Drs. Bruce McEwen, Ronald Duman, Elizabeth Gould, Rene Hen and others, it is well documented that stress can exert long-lasting changes on the brain that contribute to vulnerability to mental illness. It has been shown that some of this impact is caused by a decline in the birth of new nerve cells in the brain (or neurogenesis). In this new research, Dr. Kaufer and her team wanted to test a different hypothesis: to see if stress may alter the production of so-called helper cells, known as oligodendrocytes, in the adult brain, and if that could lead to increased vulnerability for developing stress-related disorders.

Oligodendrocytes produce the sheath of protein and fat called myelin that wraps around the axonal fibers that connect nerve cells in the brain. In multiple sclerosis, the myelin sheath, which insulates nerve fibers like the rubber coating around a wire, degrades. Dr. Kaufer followed clues that the opposite sort of effect―an abnormal increase in the production of oligodendrocytes and of myelin―might have something to do with brain pathology caused by stress.

Her team reported February 11th in Molecular Psychiatry that in experiments in living rodents (rats and mice), they succeeded in proving their hypothesis. They found that stress (as well as injection of stress hormone) caused, in addition to a decline in neurogenesis, an increase in the birth of oligodendrocytes in a portion of the hippocampus region of the brain called the dentate gyrus (DG). This part of the brain is known to be central in depression, PTSD and other stress-related disorders.

Dr. Kaufer and team believe that all past and future studies implicating problems in neurogenesis in behavioral disorders should also, in light of the new evidence, study oligodendrogenesis, the process that gives rise to the cells that produce white matter. “Our results suggest a new model in which stress may contribute to persistent vulnerability to mental illness. Accumulated stress load across the lifespan may alter the rate or extent of myelination to create a persistent, structural vulnerability.”

Read an abstract of this research study.