The HPA Axis Explained: The Impact of Fight or Flight on Psychiatric Disorders

The hypothalamic-pituitary-adrenal (HPA) axis is part of the endocrine system of hormones used to maintain homeostasis of the body; this pathway is involved in stress response

This axis links the central nervous system (CNS) with the body; the hypothalamus acts as a primary interface, (Mitrovic, 2014). Three integrating centers are involved in the pathway, first, the hypothalamus triggers the sympathetic system in the fight or flight response. When a person feels stressed this is processed by the Amygdala, an emotional processing center, which signals to the hypothalamus, signals are also sent from the midbrain or limbic system, (Health.harvard.edu, 2014). Stressful life events are also processed in the cerebral cortex that signals to the hypothalamus via the hippocampus. One of the ways information is transmitted via these pathways is through the release of the hormone cortisol.

Basal (resting) cortisol is usually measured at several points in the day due to the natural pattern of cortisol levels due to waking response and food intake

Cortisol causes ‘energy efficiency’ in the cell. This means that vital function stops so as to conserve energy. An increase in cortisol in the brain, mostly in the hippocampus, which as well as being a regulator part in the system, plays a large part in memory formation and the limbic system, has a degenerative effect. They cause an induced regression of the dendritic process, inhibit neurogenesis and contribute to neuronal death over time. (Walker and Mittal et al., 2008, pp. 189—216).

Depression has been linked to HPA dysfunction in many papers

Cortisol is known to suppress the immune system, however, cortisol receptor desensitization has been seen in major depression patients. (Van Rossum and Binder et al., 2006, pp. 681--688). Without suppression of the immune system pro-inflammatory cytokine levels would increase. These in the brain cause decreased neurogenesis and have been linked with depression as well as other degenerative mental disorders. (Leonard, 2001, pp. 305--312) Glucocorticoids strongly suppress neurogenesis in the hippocampus. Neurogenesis is required for normal functioning of the endocrine system and mice studies also showed it caused food avoidance, increased behavioral despair, and anhedonia- symptoms of depression. (Snyder and Soumier et al., 2011, pp. 458--461)

Cortisol at increased levels in patients, especially women and those with depression, decreased emotional memory formation (Abercrombie and Jahn et al., 2011, pp. 15--23)

The HPA axis’s involvement in depression has led to the development of antidepressant that directly targets the pathway, these have been effective in depression treatment for some, these, however, are effective only with some patients eluding to the complex nature of depression and it has many causes. Women are further at risk for HPA dysfunction during pregnancy and childbirth. During pregnancy, depression risk increases in mothers and there are high risks in psychotic patients of a manic episode occurring. Cortisol levels gradually increase during pregnancy and are at their highest to help in the inducement of birth (Fameli and Kitraki et al., 1994, pp. 651--659).

Dysfunction of this pathway could be linked to an evolutionary floor

The pathway is designed to keep us alert and alive during a stressful period. Originally this would be stressors such as predators, but in the modern age, stressors can be much more chronic and so long periods of exposure to high levels of cortisol are being felt; possibly explaining how the system becomes desensitized to its feedback controls. Once dysfunction occurs, in an illness such as depression, a viscous loop of dysregulation, increased stress, and eventually, changes in neurobiology mean that if not helped or treated, psychiatric consequences are difficult to overcome. The role of the HPA axis is involved in the cause and symptoms of psychiatric disorders, however, this differs between the disorder and individual patients. More research is required to establish how much of a cause it is as appose to the effect of disease onset.

 
References

1. Abercrombie, H. C., Jahn, A. L., Davidson, R. J., Kern, S., Kirschbaum, C. and Halverson, J. 2011. Cortisol’s effects on hippocampal activation in depressed patients are related to alterations in memory formation. Journal of psychiatric research, 45 (1), pp. 15--23.

2. Fameli, M., Kitraki, E. and Stylianopoulou, F. 1994. Effects of hyperactivity of the maternal hypothalamic-pituitary-adrenal (HPA) axis during pregnancy on the development of the HPA axis and brain monoamines of the offspring. International Journal of Developmental Neuroscience, 12 (7), pp. 651--659.

3. Health.harvard.edu. 2014. Understanding the Stress Response - Harvard Health Publications. [online] Available at: http://www.health.harvard.edu/newsletters/Harvard_Mental_Health_Letter/2011/March/understanding-the-stress-response [Accessed: 24 Mar 2014].

4. Leonard, B. E. 2001. Changes in the immune system in depression and dementia: causal or co-incidental effects?. International Journal of Developmental Neuroscience, 19 (3), pp. 305--312.

5. Mitrovic, I. 2014. [online] Available at: http://biochemistry.ucsf.edu/programs/ptf/mn%20links/HPA%20Axis%20Physio.pdf [Accessed: 24 Mar 2014].

6. Snyder, J. S., Soumier, A., Brewer, M., Pickel, J. and Cameron, H. A. 2011. Adult hippocampal neurogenesis buffers stress responses and depressive behaviour. Nature, 476 (7361), pp. 458--461.

7. Van Rossum, E. F., Binder, E. B., Majer, M., Koper, J. W., Ising, M., Modell, S., Salyakina, D., Lamberts, S. W. and Holsboer, F. 2006. Polymorphisms of the glucocorticoid receptor gene and major depression. Biological psychiatry, 59 (8), pp. 681--688.

8. Walker, E., Mittal, V. and Tessner, K. 2008. Stress and the hypothalamic pituitary adrenal axis in the developmental course of schizophrenia. Annu. Rev. Clin. Psychol., 4 pp. 189--216.