Childhood Stress Boosts Harmful Brain Hormone

Neglect and abuse during early childhood can cause memory loss and impaired cognitive abilities later in life by boosting the production of a hormone that harms the brain's learning and memory center, scientists said Monday.

In an experiment involving laboratory rats, researchers at the University of California at Irvine's College of Medicine showed that these stress-related dysfunctions were caused by a brain hormone called corticotropin-releasing hormone (CRH).

Until now, scientists had assumed that steroid stress hormones produced by the adrenal glands were responsible.

Dr. Tallie Baram, who led the study, said pinpointing the mechanism at work could lead to new types of treatments for stress-related damage to the brain. The study appears in the Proceedings of the National Academy of Sciences.

The researchers studied what happened in the brains of rats in an attempt to gain a better understanding of how stress in early childhood, including emotional neglect and abuse, produces enduring negative consequences in people.

"It's been shown in children and infants and also in animal models that chronic, early-life stress leads to a decline in cognitive function, particularly cognitive function that's related to the part of the brain called the hippocampus," Baram said in an interview.

"That part of the brain is responsible for learning and memory. What's been really not clear is how that happens."

Cell Death and Memory Impairment

Baram's team used a single injection of CRH, a hormone that regulates the nervous system's responses to stress, to mimic early-life stress in rats that were about two weeks old.

The rats given the injection experienced significant brain cell death — a loss of between one-tenth and one-fifth of the cells in a section of the hippocampus associated with stress-related damage.

Rats injected with the hormone were less able to perform spatial memory and object-recognition tests later in life than rats that did not receive the injections.

While the injections were given only once early in life, cell death in the hippocampus and memory problems worsened with age, the study found.

"What we are finding is that not only are we killing cells in the hippocampus, but there's also reorganization — new connections to the existing cells that make them more vulnerable," Baram said. "We create, if you will, a vicious cycle in which stress early in life can have very persistent effects throughout life."

The researchers ruled out steroid stress hormones — whose levels shoot up during stressful events — as responsible for the cell death. They said rats that had been altered to prevent them from producing these adrenal hormones still showed the memory loss and cell death produced by the CRH injection.

Baram said if scientists can find a method to block the impact of CRH on the brain, it would be possible to create new ways to prevent cognitive impairment later in life when treating certain human stress-related disorders.