Early life stress can lead to memory loss and cognitive decline in middle age

October 11, 2005

Irvine, Calif. -- Psychological stress during infancy has been found to cause early impaired memory and a decline in related cognitive abilities, according to a UC Irvine School of Medicine study. The study suggests that the emotional stress associated with parental loss, abuse or neglect may contribute to the type of memory loss during middle-age years that is normally seen in the elderly.

The study, conducted in rats, is believed to be the first to show that early life emotional stress initiates a slow deterioration of brain-cell communication in adulthood. These cell-signaling deficits occur in the hippocampus, a brain region involved in learning, storage and recall of learned memories. Study results appear in the Oct. 12 issue of the Journal of Neuroscience.

"The loss of cognitive function later in life is probably a result of both genetic and environmental factors," said study leader Dr. Tallie Z. Baram, the Danette Shepard Chair in Neurological Sciences. "While it is not yet possible to change a person's genetic background, it may be feasible to block the environmental effects, particularly of early life stress, on learning and memory later in life. These studies point to the development of new, more effective ways to prevent cognitive impairment later in life."

In their study, Baram, post-graduate researcher Kristen Brunson and colleagues found that limiting the nesting material in cages where neonatal rats lived with their mothers led to emotional stress for both mothers and pups. All evidence of this stress disappeared by the time the pups reached adulthood.

However, starting in middle age, these "graduates" of early life stress began to exhibit deficits in their ability to remember the location of objects they had seen before, as well as to recognize objects that they had encountered on the previous day. Strikingly, these difficulties worsened as the rats grew older, much more rapidly than in rats that were raised for their first week of life under typical nurturing environment.

The researchers teamed up with Gary Lynch, a UCI professor of psychiatry and human behavior and a world leader in the study of the mechanisms of learning and memory, to understand the effects early life stress had on the brain-cell activity in the rats. The normal increase in brain communication through synapses, considered to be the cellular basis for learning and memory, was found to be faulty in the middle-aged rats exposed to early life stress.

In testing these cellular abnormalities, the researchers recorded the electrical activity of brain cells, which appeared normal in young adult rats exposed to early life stress, but became very disturbed as they reached middle age. These changes in brain-cell activity were consistent with the rats' behavioral changes.

More than 50 percent of the world's children are raised under stressful conditions, as revealed by UNESCO last year. While it has been suspected that early life stress can lead to later cognitive impairment, it is not yet possible to affirm this suspicion in human studies, because children's genetic background or other confounders make these analyses too complex.

The current study allows investigators to show that the early stress itself is responsible for the cognitive decline. In addition, now that concrete deficits in brain-cell communication have been found, the new understanding of the cellular basis for how this occurs will permit the researchers to find the specific molecules involved and to design medicines to prevent the deficits.
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Eniko Kramar, Bin Lin, Yuncai Chen, Laura Lee Colgin and Theodore K. Yanagihara of UCI contributed to the study, which was supported by the National Institutes of Health.

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