Breakthrough Research Demonstrates the Brain’s Capacity to Bounce Back from Stress and Depression

From The Quarterly, Fall 2013



“The adult brain is considerably more malleable and resilient than previously believed,” says Bruce S. McEwen, Ph.D., whose groundbreaking research on the brain began in the 1960s. This is an important message––not only for people who are depressed, have an anxiety disorder or have suffered some other kind of trauma to the brain––but for all those concerned about the impact of a high-stress life on their mental sharpness as they age.



Dr. McEwen’s work has spawned more than a thousand scientific papers. In 1998 he received NARSAD Grant funding to support his quest to understand what happens when stress impacts and seems to “damage” the brain. While his research confirmed that stress does impact the brain and can cause shrinkage in the hippocampus region, for example, he also found that the impact is not necessarily permanent “damage.” He discovered the brain’s inherent capacity to adapt and remodel its architecture. His groundbreaking work effectively established what is now known as “neuroplasticity” in the field.



Dr. McEwen didn’t begin his research expecting to discover these astonishing capacities of the brain. His initial focus was the endocrine system and the hormones it generates, which help regulate bodily functions. For example, the adrenal glands, just above the kidneys, release hormones called glucocorticoids when a person experiences stress. But in 1968, Dr. McEwen discovered that cells in the brain’s hippocampus––a region important in memory and learning––had an abundance of receptors for such stress hormones.



Back then, research on hormonal action in the brain centered on the hypothalamus and the pituitary gland ––places where signals from the nervous system and the endocrine system come together. “The idea that you could have stress hormone receptors beyond the hypothalamus changed our thinking about what was going on,” Dr. McEwen says. The impact of this finding has proven to be enormous, completely changing understanding about how people respond to stress and how to treat stress-related conditions.



Cortisol, the main stress hormone, is often thought to be a “bad actor” in the human system, including in the brain. Elevated levels have now long been linked to anxiety disorders and depression. However, Dr. McEwen’s work and that of his many scientific progeny over 45 years makes plain that feeling stressed is a valuable adaptive response to adverse experiences. Stress hormones play essential roles in the body’s equilibrium by fine-tuning immune responses and the systems through which cells manufacture and adjust their energy levels. They also initiate important processes in the brain.



When cortisol and other hormones “dock” at nerve cells and along their branching projections called dendrites, which connect them in a grand network, Dr. McEwen and others have seen that under conditions of chronic stress the hippocampus can shrink. Dendritic spines––knoblike projections that provide contact points for other nerve cells––can disappear, and the “branches” of dendritic trees can shorten. Recent work in the lab has extended these observations to the amygdala, which expands under stress, and the prefrontal cortex, where stress causes dendrites and their spines to contract.



Dr. McEwen is careful to distinguish what he calls “tolerable” stress, where “the healthy person has the capacity to weather the storm,” from “toxic” stress. “It’s the difference between whether a person can bounce back or falls into a state where some kind of external help is needed” to counter the damage.



The shrinking and expansion of the hippocampus in stressed people is partly explained by a process called neurogenesis––the birth of new neurons. When people recover from depression or anxiety with the help of selective serotonin reuptake inhibitor (SSRI) antidepressants and other treatments, their recovery coincides with the formation of new neurons in a portion of the hippocampus called the dentate gyrus, which in turn promotes neuroplasticity.

 

Dr. McEwen acknowledges that as the human brain ages it has less natural resilience when under stress, but says he is heartened by research that shows the brain’s plasticity is boosted when even a sedentary elderly person begins to exercise five days a week. Studies now suggest that even normal cognitive decline can, in many cases, be slowed through exercise and regular socializing. (This has been found to spur neurogenesis, and not only in the elderly). Similarly, when a depressed or anxious person is placed in an environment that is more interesting and supportive, plasticity seems to be enhanced, and with it, resilience.



Treatments for depression and anxiety succeed most often when a patient takes a neurogenesis-promoting antidepressant medication and receives individually tailored cognitive behavioral therapy (a specific type of “talk therapy”). But antidepressants don’t always work, and one current objective of the McEwen lab is to develop faster-acting antidepressants and medications that enhance naturally occurring “neuroprotective factors.” Such factors include proteins called neurotrophins that promote the brain’s natural plasticity and resilience. It is hoped that such targeted medications will promote brain plasticity to more effectively restore healthy brain function across many psychiatric disorders.