Effects of chronic stress in human brain

Explainer: How chronic stress affects the brain

Depending on intensity and duration, the biological effects of stress are either favourable or unfavourable and several researchers have been specifically exploring how chronic stress affects the brain. According to published studies, too much and prolonged stress alters brain functions and brain structures, resulting in cognitive and mental health problems.

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 amygdala and hippocampus—another brain areas involved in the processing and regulation of emotions. Thus, based on these studies, children and adolescents who are subjected under too much stress for a prolonged period are more likely grow up with behavioural problems and social difficulties.

Researchers Carmin Sandi et al reiterated that chronic stress in adults is a risk factor for the development of psychopathologies characterised by cognitive impairments and deregulated social behaviours. In their study centred 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 behaviour, 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. Further study by researchers Jason J. Radley et al revealed that older animals with high levels of corticosterone 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 rendering their working memory impaired.

Nonetheless, animal studies suggest that chronic stress is associated with alteration in the structure of several brain areas, particularly the hippocampus and prefrontal cortex, which in turn, result in impairment of long-term and working memories.

The studies above have also associated chronic stress with reduced brain connectivity due to loss of synapses between neurons. Another study by Daniela Kaufer et al reported that the effects of chronic stress do not rest alone in alterations in brain connectivity but also in predisposition to mental disorders. According to their initial review of related literatures, 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 muchand prolonged stress, Kaufer et al reported that chronic stress triggers oligodendrogenesis—a process that makes neural stem cells mature into myelin-producing cells or oligodendrocytes—and decreases neurogenesis—a process that makes neural stem cells mature into neurons. The result is excess fatty myelin sheath and less 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 is comprised of axons, which create a network of fibres 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 a key role for oligodendrocytes in long-term and perhaps permanent changes in the brain that could set the stage for later mental problems, particularly anxiety and mood disorders.

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. The activation of this protein 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 signalling and thus, depression.

The effects of chronic stress on 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 overall health and wellbeing of individuals. Not only did these studies draw associations between stress and cognitive or mental health problems, they have also established the mechanism behind these associations at the biological, cellular, and molecular levels.

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 centre 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 mood disorders such as anxiety and depression, among others.

Further details of the study of Hanson et al are in the article “Early stress is associated with alterations in the orbitofrontal cortex: A tensor-based morphometry investigation of brain structure and behavioural risk” published in 2010 in The Journal of Neuroscience. Details of another study of Hanson et al are in the article “Behavioural problems after early life stress: contributions of the hippocampus and amygdala” published in 2015 in the journal Biological Psychiatry.

More details of the study of Sandi et al are in the article “Role for MMP-9 in stress-induced downregulation of nectin-3 in hippocampal CA1 and associated behavioural alterations” published in 2014 in the journal Nature Communications. Details of the study of Radley et al are in the article “Adrenocortical status predicts the degree of age-related deficits in prefrontal structural plasticity and working memory” published in 2014 in The Journal of Neuroscience.

Details of the study of Kaufer et al are in the article “Stress and glucocorticoids promote oligodendrogenesis in the adult hippocampus” published in 2014 in the journal Molecular Psychiatry. Further details of the study of Ferguson et al are in the article “The psychobiology of depression and resilience to stress: Implications for prevention and treatment” published in 2005 in the journal Clinical Psychology.