March 15, 2025	PSY 340 Brain and Behavior Class 30: Stress and Health

Think of the kinds of stress do you or other college students experience?

Demands of work and school at the same time?
Taking care of children or sick parents while holding down a job?
Demands at work that you give 110%?
Taking too many classes?
Personal life-threatening illness? Other chronic illness?
COVID-19!!!!!
War in Ukraine & threat of nuclear war!!

I. Stress and the Autonomic Nervous System

• During the 1950s, the Czech-Canadian physiologist, Hans Seyle (1907-1982), developed the first important theories regarding the relationship between stress and health.
    
• Stress = the response of the body to any demand put upon it. Note that the demands can be not only physical (e.g., the effects of weather, cold, heat, etc.), but also psychological.
    
• Types of stress: pleasant (e.g., getting married) and unpleasant (e.g., death of a loved one, financial difficulties)
    
• General Adaptation Syndrome: A generalized response by the body to continued stress which comes in three stages
• Stage 1: Alarm = sympathetic nervous system readies body for brief emergency
  
• Stage 2: Resistance = adrenal gland secrete cortisol & other hormones to promote alertness, fight infections, and heal wounds
  
• Stage 3: Exhaustion = after prolonged stress, body becomes tired, inactive, and vulnerable to infections, etc.
  

II. Stress, the HPA Axis, & the Immune System

• Stress activates two body systems: the (1) autonomic nervous system and (2) the HPA Axis (hypothalamus-pituitary gland-adrenal cortex)|
   
  
• The hypothalamus sends CRF (corticotropin releasing factor) to the pituitary gland which secretes ACTH (adrenocorticotropic hormone) into the bloodstream which, when it reaches the adrenal cortex, stimulates the production of cortisol. When operating normally, elevated levels of cortisol serve in a negative feedback loop to suppress the further production of CRF and ACTH. Thus, cortisol inhibits its own secretion. The hippocampus appears to be a major neural structure to inhibit the HPA axis; hence, damage to the hippocampus would be expected to upset the normal functioning of the axis.
    
• Cortisol (aka hydrocordisone) mobilizes body's energies by increasing blood sugar and metabolism rate (while lowering rate of protein synthesis). In the short-term this is helpful, but in the long-term, this is damaging to the body. Recall that cortisol is a "catabolic steroid" which breaks down proteins including muscle tissue.
  
• Chronic stress in which cortisol is elevated for long periods of time has been associated with a range of health problems including type 2 diabetes and metabolic syndrome (increased blood pressure, high blood sugar, excess body fat around the waist, and abnormal levels of cholesterol or triglycerides in the blood). In addition to diabetes, metabolic syndrome increases the risk of heart disease and stroke.
  

• Cortisol & the Brain: Negative Effects (not in book)

• In addition to the effects on blood sugar, protein synthesis, and metabolism rate, the cortisol molecule easily crosses the blood-brain barrier and affects the central nervous system, particularly areas having to do with cognition (Ouanes & Popp, 2019). 
  

• Functional Effects.
  

• Research has consistently found that high levels of circulating cortisol among otherwise healthy older adults without dementia is associated with poorer episodic memory.
  

• Structural Effects.
  

• Among the elderly, high cortisol levels are associated with a smaller hippocampus and greater memory problems.
  
• Other studies of healthy middle-age adults find high cortisol levels associated with decreased volume of various brain areas involved in cognition including decreased total brain volume (especially decreased occipital & frontal grey matter) as well as microstructural changes in the corpus callosum and other structures [Oaunes & Popp, 2019, p. 3; Echouffo-Tcheugui, J. B. et al (2018)]. 
  

• Alzheimer's Disease (AD)

• The impact of stress in elevating the H-P-A Axis into chronic over-activity has been hypothesized to be a risk for the development of AD or speeding up the neural deterioration of patients with AD. 
  

• Among individuals with varying levels of Alzheimer's disease, high levels of cortisol are associated with both lower overall brain volume as measured by MRI and lower levels of brain metabolism as measured by PET scanning ("hypometabolism"; Wirth et al., 2019). "Taken together, our findings are convergent with the idea that HPA axis activation may be a vigorous mechanism that accelerates AD pathogenesis. The study shows detrimental relationships between stress hormone levels and brain integrity within regions sensitive to AD pathology across the AD spectrum" (Wirth et al., 2019, p. 23)

• Other researchers have found that high cortisol levels are associated with a faster decline in AD patients while cortisol levels are an accurate biomarker for deterioration from mild cognitive impairment to full AD (Oaunes & Popp, 2019).
  

  Effects of Stress on the Immune System

Cytokines: When we are sick, T-cells (a type of immune system cell in our blood) release chemicals called cytokines (e.g., interleukin-1). These combat infections and also communicate with the brain to promote appropriate nervous system responses. As we saw in an earlier chapter, cytokines stimulate receptors of the vagus nerve which, in turn, relays messages to the hypothalamus and hippocampus to release cytokines within the brain, too.

• These prompt the development of a fever
• Increased sleep, decreased muscle activity, and decreased sex drive conserve energy
• Decreased appetite might be helpful by curbing the need to work to provide food

Strong, inescapable, and temporary stresses trigger similar responses to those caused by an illness: fever, sleepiness, decreased appetite & sex drive

Brief stress causes SNS arousal and HPA Axis arousal: in the short run, these strengthen the body.

Long-term or chronic stress, anger, or anxiety leads to harm of the body, e.g.,

• Prolonged cortisol release seems to limit the synthesis of immune system cell proteins, e.g., people living near the Three-Mile Island nuclear plant accident (1979) over the subsequent year had decreased immune system cells

• Antarctic researchers over 9 months of cold, dark, and isolation show reduced T-cells functions (ca. 50% of normal).

• Exposure to common cold viruses does not lead to increased illness for those subject to less than a month of stress; individuals with 4 or more weeks of stress are more likely to become sick.

• Recent research of children who had been subjected to severe child maltreatment by their parents by the age of 3 demonstrated significant negative alterations in the overall connectivity patterns in the development of the white matter of their brains (as compared to matched control children; Puetz et al., 2017). The researchers note that such findings are in line with research showing that high levels of HPA axis activation and chronic exposure to cortisol affects neural development in children.  
  

• Chronic stress may increase the likelihood of developing cancer (Dai et al., 2020; Tausk, 2023) including the spread of breast cancer to the bones (Lourenço et al., 2022)
  

References

Dai, S., Mo, Y., Wang, Y., Xiang, B., Liao, Q., … Zeng, Z. (2020). Chronic stress promotes cancer development. Frontiers in Oncology, 10, 1492. https://doi.org/10.3389/fonc.2020.01492

Echouffo-Tcheugui, J. B. et al (2018) Circulating cortisol and cognitive and structural brain measures. Neurology, 91(21). https://doi.org/10.1212/WNL.0000000000006549

Lourenço, C., Conceição, F., Jerónimo, C., Lamghari, M., & Sousa, D. M. (2022). Stress in metastatic breast cancer: To the bone and beyond. Cancers, 14, 1881. https://doi.org/10.3390/cancers14081881

Ouanes, S., & Popp, J. (2019). High cortisol and the risk of dementia and Alzheimer’s disease - A relview of the iterature. Frontiers in Aging Neuroscience. https://doi.org/10.3389/fnagi.2019.00043

Puetz, V. B., Parker, D., et al. (2017). Altered brain network integrity after childhood maltreatment: A structural connectomic DTI-study. Human Brain Mapping, 38(2), 855-868. https://doi.org/10.1002/hbm.23423

Tausk, F. (2023). Psychoneuro-oncology: How chronic stress grows cancer. Clinics in Dermatology. https://doi.org/10.1016/j.clindermatol.2023.03.008

Wirth, M., Lange, C., & Huijgers, W. (2019). Plasma cortisol is associated with cerebral hypometabolism across the Alzheimer's disease spectrum. Neurobiology of Aging, 84, 80-89. https://doi.org/10.1016/j.neurobiolaging.2019.08.00

---

The first version of this page was posted on April 7, 2005.