Surprising Ways that Stress Affects Your Brain and Immunity

Neuroscience research uncovers the complex effects of stress on brain and body.

Posted Jun 30, 2019

CFCF/Wikimedia Commons
Source: CFCF/Wikimedia Commons

People who have early trauma or those who are chronically stressed often have difficulty remembering things, or they may find it difficult to concentrate, prioritize, and make decisions. These effects may be the result of brain changes associated with severe and/or chronic stress.

Neuroscientists are developing a more advanced understanding of stress-related brain changes based on research with animals and humans. These include both structural changes in brain volume, changes in the release of hormones and neurotransmitters, and the effects of stress on inflammation. Below are some highlights from this research

The Hippocampus and Medial Prefrontal Cortex

Exposure to both early life stress (e.g., child abuse) and chronic stress (e.g., unhappy marriage, excessive work demands) has been linked to reduced volume in two major areas of the brain: the hippocampus and medial prefrontal cortex. 

The hippocampus is a seahorse-shaped structure located in the middle part of the temporal lobe. It is involved in storing memories in an organized and sequential way, as well as in spatial navigation. 

The medial prefrontal cortex is an area in the frontal lobe of the brain that is involved in processing information about the self and others, regulating emotional responses to stress, evaluating risk and reward, and making decisions based on past experiences and aspects of the current situation. 

Reduced volume in these areas can result in impaired social cognition, difficulty making decisions, difficulty regulating emotions, and difficulty in learning from experience, among other functions.

Hormones and Neurotransmitters

1. The HPA axis and cortisol

Chronic stress has been shown to interfere with the workings of the HPA axis (hypothalamic-pituitary-adrenal axis) which are areas of the brain involved in generating a biobehavioral response to stress. The HPA axis is involved in both the production and regulation of cortisol, a stress hormone that alerts and activates the body to respond to stress (e.g., increased heart rate, flow of blood to large muscles, glucose release).

Too much stress exposure can make the system insensitive to the signaling function of cortisol, resulting in either too much cortisol, disruption of its daily rhythm (cortisol is normally higher in the morning and goes down in the evening), or depletion of cortisol. Dysregulated cortisol release can result in under- or overreaction to stress.

Cortisol communicates with the immune system to regulate inflammation. When this function is impaired, inflammatory responses may get out of control.

2. Gamma-aminobutyric acid (GABA)

GABA is a brain neurotransmitter that has been shown to modulate (decrease) anxiety. In a more general way, GABA is an inhibitory neurotransmitter that helps to create a balance between excitation and inhibition in the brain.

In humans with anxiety or stress-related disorders, GABA levels are reduced in the brain, particularly in the prefrontal cortex. A 2015 study of human exposure to the threat of shock (a stress condition) versus no threat (safety condition) showed that GABA levels in the medial prefrontal cortex decreased by almost 18 percent in the threat of shock condition, compared to the safety condition. This result mirrors those of rodent studies, which have also shown decreased GABA neurotransmission in response to acute stress.

Rodent studies have also shown a link between chronic stress (e.g., restraint, immobilization) and reduced GABA signaling in the amygdala, which is a part of the brain involved in fear learning and responding rapidly to threats. More research is needed to confirm this effect of chronic stress on amygdala GABA in humans.

Stress and the Immune System

The effects of stress on the immune system are complex, and the effects differ for acute (time-limited) stress, chronic stress, mild stress, and severe stress. Acute stress can actually improve immune function in the short-term, whereas chronic stress can suppress it, making us more susceptible to colds and flu. 

Stress can facilitate the release of substances known as pro-inflammatory cytokines. Pro-inflammatory cytokines help us fight off disease or infection in the short-term. But if the stressor goes on too long or is too severe, it can result in chronic inflammation which makes us more prone to inflammatory diseases (including cardiovascular disease, diabetes, and Parkinson’s disease).

According to Liu et al. (2017):

“Both pro-inflammatory and anti-inflammatory mechanisms depend on the type and intensity of stressors. Acute stressors seem to enhance immune function, whereas chronic stressors are suppressive. Intense stressors over-activate the immune system, leading to the imbalance of inflammation and anti-inflammation. Reports from different labs have confirmed pro-inflammation induced by stress, including C-reactive protein (CRP), IL-6, TNFα, IL-1β and the transcription factor of “nuclear factor kappa B (NF-κB)” (Miller et al., 2009).”


In summary, acute and chronic stress have varying and complex effects on brain structure and function. We still do not fully understand all of these complex effects and more research needs to be done in both animals and humans to fully understand what types and duration of stress produce which effects, 

The major effects of stress described in this article are:

  • reduced volume in the hippocampus (memory and spatial ability)
  • reduced volume in the medial prefrontal cortex (decision-making, social cognition)
  • disruption of cortisol release and regulation by the HPA axis
  • reduced GABA transmission in the prefrontal cortex and amygdala
  • both pro-inflammatory and anti-inflammatory effects in the immune system
  • chronic inflammation that can result from severe stress and increases the risk for many diseases.


Belleau, E.L., Treadway, M.T. and Pizzagalli, D.A. The impact of stress and major depressive disorder on hippocampal and medial prefrontal cortex morphology. Biological Psychiatry 18 (2018), 10.1016/j.biopsych.2018.09.031. 

Liu, Y.-X. Wang, C.-L. Jiang Inflammation: the common pathway of stress-related diseases. Front. Hum. Neurosci., 11 (2017), p. 316, 10.3389/fnhum.2017.00316

Liu, Z. P., Song, C., Wang, M., He, Y., Xu, X. B., Pan, H. Q., et al. (2014). Chronic stress impairs GABAergic control of amygdala through suppressing the tonic GABAA receptor currents. Mol. Brain 7:32. doi: 10.1186/1756-6606-7-32