Wednesday, October 16, 2013

The Relationship between Stress and Depression

The relationship between stress and depression is complex (Laureate Education, Inc., 2012). It is bidirectional in that stress can cause depression and depression can cause and exacerbate stress (Laureate Education, Inc., 2012; Wilson & Warise, 2008). In an effort to understand the inextricable interconnectedness of the immune system and depression, one might wonder if depression, like other diseases, is a product of inflammation. In any event, inflammation and the immune response are implicated in depression. Although depression may lead to inflammation (Wilson & Warise, 2008) but inflammation can lead to depression (Musselman et al., 2001).

Factors that Influence Depression

One of the body's primary responses to stress is the surge of cytokines, specifically interleukins and interferons, through the blood to defend the body against pathogenic invaders. The body's cytokine immune response has been implicated in depression as well as in some autoimmune diseases (Wilson & Warise, 2008).

Cytokines Causing Symptoms of Sickness

Cytokines are immune proteins that regulate the immune system, especially during a stress response (Wilson & Warise, 2008). This dispatch can cause overall feelings of fatigue and malaise that can contribute to depression. When stress forces this immune response, the resulting fatigue and reduced motivation can cause frustration, anxiety, and additional stress. Stress has been defined as the increasing incongruence between the needs of the individual and his or her environment (Storch, Gaab, Küttel, Stüssi, & Fend, 2007). For example, if an individual's stress level has positioned her on the brink of depression, the growing difference between her ability to accomplish her daily responsibilities with her suboptimal level of physical energy and decreased motivation could cause further frustration and problems at work, exacerbating her level of stress, and contributing to the development of depression. This is an example of the bidirectional character of the relationship between the stress and depression.

Cytokines Affect on Serotonin

Another influence of cytokines is their inflammatory effect on the neurotransmission of serotonin, which plays an important role in psychological health and well-being (Dabhar, 2011; Salih & Feyza, 2012; Wilson & Warise, 2008). Inflammation has an effect on the body's ability to manufacture serotonin. Further, cytokines have an influence on the other neurotransmitters dopamine and norepinephrine, both of which are integral to well-being. When cytokines are flushed into the blood stream by the immune system, they activate an enzyme called IDO, which degrades serotonin (Müller & Schwarz, 2007). In addition, this enzyme has an effect on tryptophan, which is the precursor to serotonin. With lower levels of serotonin in the system, the individual is more susceptible to depression. In effect, the inflammation from the immune response destroys serotonin (Müller & Schwarz, 2007). When cytokines are administered as a medical treatment for disease, side effects are known to cause social problems, insomnia, and a decline in cognitive functioning, all of which are symptomatic in depression (Raison, Demetrashvili, Capuron, & Miller, 2005).

Depression and the Immune and Inflammatory Response Systems

Depression has a powerful affect on the immune and inflammatory response systems. It increases stress hormones such as cortisol and other inflammatory cytokines such as IL-6, and the aforementioned IDO (Müller & Schwarz, 2007). These substances decrease the body's ability to heal, which can increase vulnerability to other diseases, even some types of cancer and autoimmune diseases such as lupus and osteoporosis. IL-6 has been implicated in decreased immune functioning and chronic inflammation and has been frequently studied in depression (Salih & Feyza, 2012). High levels of IL-6 have been found in depressed patients as well as in cancer patients. In effect, an increase in cytokines typically induces sickness behaviors, and the same increase has been found in depressed individuals (Müller & Schwarz, 2007; Salih & Feyza, 2012).

On a personal note, it is somewhat exciting to learn about the implications of inflammation in depression. However, my excitement is tempered by considering the complex relationship between the environment, individual genetics and perceptions, and biology, and the fact that likely there is not a sole cause of depression. Maintaining a holistic perspective continues to benefit research, individual case conceptualization, and the development of interventions for depression (Gutman, & Nemeroff,, 2011; Raison et al., 2005).


Dhabhar, F. S. (2011). Effects of stress on immune function: Implications for immunoprotection and immunopathology. In R. J. Contrada & A. Baum (Eds.), The handbook of stress science: Biology, psychology, and health (pp. 47–63). New York, NY: Springer Publishing Company.

Gutman, D. A., & Nemeroff, C. B. (2011). Stress and depression. In R. J. Contrada & A. Baum (Eds.), The handbook of stress science: Biology, psychology, and health (pp. 345–357). New York, NY: Springer Publishing Company.

Laureate Education, Inc. (2012). Stress, the immune system, chronic illness, and your body. [Handout].

Müller, N., & Schwarz, M. J. (2007). The immune-mediated alteration of serotonin and glutamate: Towards an integrated view of depression. Molecular Psychiatry, 12(11), 988-1000. doi: 10.1038/

Musselman, D. L., Miller, A. H., Porter, M. R., Manatunga, A., Gao, F., Penna, S., & ... Nemeroff, C. B. (2001). Higher Than Normal Plasma Interleukin-6 Concentrations in Cancer Patients With Depression: Preliminary Findings. American Journal of Psychiatry, 158(8) 1252-1257.

Salih, G., & Feyza, A. (2012). Inflammation in depression: the role of cytokines. Journal Of Marmara University Institute Of Health Sciences, 2(3), 103-107.

Wilson, D. R., & Warise, L. (2008). Cytokines and their role in depression. Perspectives in Psychiatric Care, 44(4), 285–289.

Zhang, S. (2012). A biological explanation for depression: The role of interleukin-6 in the aetiology and pathogenesis of depression and its clinical implications. Australian Medical Student Journal, 3(2), 24-26.

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