Studies: Effects of Chronic Stress in the Brain

Studies: Effects of Chronic Stress in the Brain

The biological effects of stress can be either favorable or unfavorable, depending on its intensity and duration. Several researchers have been specifically exploring how chronic stress affects the brain. Published studies have revealed that too much and prolonged stress results in cognitive impairments and mental health because it alters brain functions and brain structure.

Understanding What Chronic Stress Does to Our Brain

Alterations in the Brain Functions and Structure

The study of Jamie L. Hanson et al. revealed that early stress is associated with alterations in the orbitofrontal cortex—an area in the prefrontal cortex region of the brain involved in the cognitive processing of decision-making. Another study by Hanson et al. also revealed that early life stress results in the shrinkage of the amygdala and hippocampus—areas of the brain involved in the processing and regulating emotions. Thus, based on these studies, children and adolescents under too much stress for a prolonged period are more likely to grow up with behavioral problems and social difficulties.

Researchers Carmin Sandi et al. reiterated that chronic stress in adults is a risk factor for developing psychopathologies characterized by cognitive impairments and deregulated social behaviors. Their study centered on investigating rat models both in vitro and in vivo. They found out that when triggered by stress, an enzyme called MMP-9 attacks the synaptic regulatory molecule nectin-3 in the hippocampus region resulting in loss of adherence between neurons or synaptic plasticity.

Because the phenomenon transpires in the hippocampus, a region involved in long-term memory, cognitive abilities, and behavior, the outward manifestations of nectin-3 downregulation include loss of sociability and peer avoidance, as well as impaired memory and comprehension of information.

Multiple animal studies have linked high levels of the stress hormone corticosterone—similar to the human stress hormone cortisol—with age-related structural and functional decline in the hippocampus. A study by Jason J. Radley et al. showed that older animals with high corticosterone levels had fewer synaptic connections between prefrontal cortex cells than other older animals with lower levels of the stress hormone. In other words, older animals with high corticosterone levels have “older” frontal cortexes, thus impairing their working memory.

Prolonged exposure to stress fundamentally alters the structure of the hippocampus and prefrontal cortex, which in turn, impairs long-term and working memories. The studies above have also associated chronic stress with reduced brain connectivity due to loss of synapses between neurons.

Link Between Chronic Stress and Mental Health Problems

Another study by Sundari Chetty et al. reported that the effects of chronic stress do not rest alone in alterations in brain connectivity but also in predispositions to mental disorders. According to their initial review of the literature, stress can exert long-lasting changes in brain structure. People suffering from stress-related illnesses, including post-traumatic stress disorder, have differences in the amount of gray matter versus white matter. However, the mechanism behind these stress-induced changes remains unclear.

In a series of experiments that involved observing the hippocampus of rodents while under too much and prolonged stress, Kaufer et al. reported that chronic stress triggers oligodendrogenesis and decreases neurogenesis. Oligodendrogenesis is a process in which neural stem cells mature into myelin-producing cells or oligodendrocytes. Neurogenesis is another process in which neural stem cells mature into neurons. The result is excess fatty myelin sheath and fewer neurons or, in other words, more white matter and less gray matter in some areas of the brain.

Gray matter consists mostly of neurons responsible for storing and processing information, while white matter comprises axons, which create a network of fibers that interconnect neurons. White matter gets its name from the white, fatty myelin sheath that surrounds the axons and speeds the flow of electrical signals from cell to cell. The imbalance between grey matter and white matter disrupts the delicate balance and timing of communication within the brain.

The findings suggest the possible role of oligodendrocytes in long-term and potentially permanent changes in the brain that could set the stage for later mental health problems. Note that there is also a biological link between stress and anxiety, and depression. Stephen S. G. Ferguson et al. reported that stress leads to the activation of a protein known as corticotropin-releasing factor receptor 1 or CRFR1. Its activation does not only trigger anxiety but also promotes the release of specific types of serotonin receptors called 5-HTRs on cell surfaces in the brain. Too much 5-HTRs can cause abnormal brain signaling.

The effects of chronic stress in the brain are multifold. While stress is an unavoidable fact of life, too much can have profound cognitive and mental health implications. The studies above form part of a growing body of research about the role of chronic stress in the overall health and well-being of individuals. Not only did these studies draw associations between stress and cognitive or mental health problems, but they have also established the mechanism behind these associations at the biological, cellular, and molecular levels.

Conclusion: How Intense and Prolonged Stress Affects the Brain

How chronic stress affects the brain? The referenced studies revealed that chronic stress triggers biological processes that alter brain function and brain structure.  A key takeaway from these studies centers on taking into consideration the underlying external and biological mechanisms of stress in the possible treatment and management of specific mental health problems—to include cognitive impairment, poor long-term or working memory, and mental health problems such as anxiety and depression, among others.

FURTHER READINGS AND REFERENCES:

  • Anderson, R. M., Birnie, A. K., Koblesky, N. K., Romig-Martin, S. A., and Radley, J. J. 2014. “Adrenocortical Status Predicts the Degree of Age-Related Deficits in Prefrontal Structural Plasticity and Working Memory.” Journal of Neuroscience. 34(25): 8387-8397. DOI: 1523/jneurosci.1385-14.2014
  • Chetty, S., Friedman, A. R., Taravosh-Lahn, K., Kirby, E. D., Mirescu, C., Guo, F., Krupik, D., Nicholas, A., Geraghty, A. C., Krishnamurthy, A., Tsai, M.-K., Covarrubias, D., Wong, A. T., Francis, D. D., Sapolsky, R. M., Palmer, T. D., Pleasure, D., and Kaufer, D. 2014. “Stress and Glucocorticoids Promote Oligodendrogenesis in the Adult Hippocampus.” Molecular Psychiatry. DOI: 1038/mp.2013.190
  • Hanson, J. L., Chung, M. K., Avants, B. B., Shirtcliff, E. A., Gee, J. C., Davidson, R. J., and Pollak, S. D. 2010. “Early Stress Is Associated with Alterations in the Orbitofrontal Cortex: A Tensor-Based Morphometry Investigation of Brain Structure and Behavioral Risk.” Journal of Neuroscience. 30(22): 7466-7472. DOI: 1523/jneurosci.0859-10.2010
  • Hanson, J. L., Nacewicz, B. M., Sutterer, M. J., Cayo, A. A., Schaefer, S. M., Rudolph, K. D., Shirtcliff, E. A., Pollak, S. D., and Davidson, R. J. 2015. “Behavioral Problems After Early Life Stress: Contributions of the Hippocampus and Amygdala. Biological Psychiatry.” 77(4): 314-323. DOI: 1016/j.biopsych.2014.04.020
  • Southwick, S. M., Vythilingam, M., and Charney, D. S. 2005. “The Psychobiology of Depression and Resilience to Stress: Implications for Prevention and Treatment.” Annual Review of Clinical Psychology. 1(1): 255-291. DOI: 1146/annurev.clinpsy.1.102803.143948
  • Van der Kooij, M. A., Fantin, M., Rejmak, E., Grosse, J., Zanoletti, O., Fournier, C., Ganguly, K., Kalita, K., Kaczmarek, L., and Sandi, C. 2014. Role for MMP-9 in Stress-induced Downregulation of Nectin-3 in Hippocampal CA1 and Associated Behavioural Alterations. Nature Communications. 5(1). DOI: 1038/ncomms5995