Its known that chronic stress in adolescents has a stronger effect on the brain than in adults, but not that much is known about the cause and effect taking place. Now, researchers at The University of Buffalo have looked into the molecular level and found definitive proof.

Zhen Yan, PhD, a professor in the Department of Physiology and Biophysics in the UB School of Medicine and Biomedical Sciences, and her team published the findings in this month’s edition of Neuron. The say:

We have identified a causal link between molecules and behaviors involved in stress responses, it’s the first time that the loss of a glutamate receptor has been causally linked to the negative effects of chronic or repeated stress.”

She has also uploaded video about the work at

In previous research, Yan and her colleagues discovered that acute stress helps to improve memory, which makes sense from an animalistic survival point of view. That work was published in 2009. Now, however, they have discovered the opposite.

Her latest work was carried out using male rats as test subjects. The rats were chosen with an age that corresponded to human adolescence, a time when the brain is extremely susceptible to stress. The prefrontal cortex is not fully developed until the age of 25 in humans, and undergoes dramatic changes during the teenage years. The prefrontal cortex has been described as the Chief Executive Office of the brain, controlling memory, decision making and attention.

Yan, and her colleagues found that repeated stress caused the glutamate receptor to lose function, resulting in a large degree of impairment in the animal’s ability to remember and recognize objects. This was not something they expected or had seen before, because the previous research on humans did not show the same results.

Yan says :

“Because dysfunction in the prefrontal cortex has been implicated in stress-related mental illness, this research identifying how stress affects prefrontal cortical functions will help further unravel how and why mental illnesses occur and how to treat them.”

More interestingly, though, Yan also provides somewhat of a cure to the problem. By inhibiting the enzymes that caused the loss of the glutamate receptor, much of the cognitive impairment was recovered. This kind of work is interesting and important in treating diseases such as psychosis, depression, anxiety and schizophrenia. In fact, one of the newer antipsychotics, lurasidone, (trade name Latuda) does just that. But, she notes, many of these drugs also affect other important neurotransmitter systems, as well.

Yan concludes that :

“… If, based on this research, we can begin to target the glutamate system in a more specific and effective way, we might be able to develop better drugs to treat serious mental illness … While there have been many behavioral studies about stress, understanding stress at a molecular level is key to developing strategies to prevent stress-induced behavioral deficits … In the end, it has to be boiled down to molecules. Without knowing why something happens at a molecular level, you cannot do anything about it.”

In addition to Yan, the co-authors of the study are: Eunice Y. Yuen, PhD, research assistant professor, Jing Wei, PhD, research scientist, Wenhua Liu, PhD, research scientist, Ping Zhong, PhD, research scientist, and Xiangning Li, PhD, postdoctoral associate, all in the Department of Physiology and Biophysics in the UB School of Medicine and Biomedical Sciences. The research was funded by the National Institutes of Mental Health of the NIH.

Written by Rupert Shepherd