From The Quarterly, Summer 2014

For years, psychiatrists and scientists who study the brain have noted that a highly stressful experience or periods of chronic stress early in life not only can cause behavioral and emotional problems at the time of the stress, but also make many people vulnerable to developing stress-related disorders into adulthood.

The biological explanation for this lingering susceptibility is one of brain science’s great mysteries. A team of researchers—led by Daniela Kaufer, Ph.D., of the University of California, Berkeley, a recipient of a NARSAD Young Investigator Grant in 2009—tested a theory that they report has held up well in experiments. Their findings were explained in a paper appearing in Molecular Psychiatry on February 11, 2014.

The team, which also included 2004 NARSAD Distinguished Investigator Grantee Robert M. Sapolsky, Ph.D., of Stanford University, set out to determine if stress alters the process by which the adult brain and central nervous system produce an essential class of cells called oligodendrocytes. These “helper” cells manufacture the fatty coating that insulates nerve sheaths in much the same way that a rubber coating protects copper wires. “White matter” in the brain gets its name from the abundance of this light-colored nerve fiber coating, called myelin.

In multiple sclerosis, oligodendrocytes die or are unable to make myelin; the lack of nerve insulation profoundly affects the normal function of both the brain and connected motor systems. The question Dr. Kaufer and colleagues explored was whether oligodendrocyte production was affected by stress. They were able to demonstrate that environmental stress caused an abnormally high production of oligodendrocytes in the dentate gyrus* (DG) region of the brain. This part of the brain’s hippocampus is central in memory and emotion, and one of the few places in the brain where new neurons are generated in adults.

Stress (as well as direct injections of stress hormone) caused fewer new nerve cells to be born in the DG in experiments with rats. For the first time ever, the team was able to show that stress (and stress hormone injections) also increased oligodendrocyte production in the DG. In test tube experiments, Dr. Kaufer’s team went on to show that stress hormone injection caused stem-like cells that usually give rise to neurons to turn on a transcriptional program that increases the rate at which oligodendrocytes are generated. By blocking these cells’ docking ports for stress hormone—disabling their capacity to take it in—the overproduction of mature oligodendrocytes was prevented.

Taken together, these experiments provide an intriguing potential explanation for why adults who were traumatized or regularly stressed as youths carry an abnormally high risk of developing stress-related disorders.“Stress may alter how the hippocampus functions, by promoting the production of oligodendrocytes,” the scientists say. “We suggest that this alters the composition of cells in that region and changes its white-matter structure. This may create a persistent, white matter structural vulnerability to mental illness.”