Depression as an Immune Response

By Julia Malkowski, ND, DC | December 8, 2020

During the summer of 2020, 40% of adults reported struggling with depression or seriously considered suicide. The pandemic, subsequent lockdown measures, financial and social implications have struck at the very determinants of mental health. Depression is multifaceted, influenced by many factors including psychological, biological and social. A deep-rooted theory of depression, the pathogen host theory, may give us context and clues as how to address the modern predicament we find ourselves in. In this framework, the biological factors contributing to depression may be addressed as well.

Did depression develop out of an appropriate response to sickness? During hunter-gather times, people lived active communal lives. When someone was sick, they needed to lose interest in the external environment, withdraw from the tribe and conserve energy by decreasing activity. This response focuses metabolic resources to fight infection, while isolation prevents the spread of disease. Genes associated with depression are also those genes associated with our ability to fight infections and our immune system. Depression and illness share genetic variants including polymorphisms in the genes for interleukin (IL)-1β, IL-6, IL-10, monocyte chemoattractant protein-1, tumor necrosis factor-alpha, C-reactive protein, and phospholipase A2.  

Biologically speaking, depression and sickness share many factors. Those with depression and illness have increased body temperatures, even more pronounced at night. Well established inflammatory markers CRP and IL-6 have been shown to be increased by 50% in depressed individuals. Inflammatory cytokines such as interferon-alpha are known to cause depression and are inhibited by antidepressants. A proposed mechanism of action for anti-depressants is the reduction of IL-10 to decrease inflammation. The immune modulator, zinc was shown to be 12% lower in depressed individuals, incrementally associated with severity. Iron is decreased as an immune response to starve off bacteria, and low iron has been associated with depression. While critical for the immune system, research shows a link between depleted serum vitamin D and symptoms of depression.

Fast paced living, inadequate physical activity, financial stress, solitary dwelling, and processed food poises modern life far from the active, communal lives of hunter gather times. The processed standard American diet (SAD) is associated with gut dysbiosis. Gut dysbiosis is associated with inflammation, depression and altered immune response. Notably, the Bacteroides family has been shown to be associated with depression. While healthy levels of Lactobacillus and Bifidobacterium are associated with a healthy mental state and innate immune response. 

Conserving energy and withdrawing from society may be an appropriate response to illness, yet this is compounded via a constant low level of inflammation due to modern living which may contribute to depression even during non-pandemic times. While some factors contributing to depression such as genetic polymorphisms are stagnant, epigenetics may be addressed via nutrition and lifestyle. Appropriate recommendations of optimal nutrition and decreased consumption of a SAD may inhibit an inflammatory cascade. Evaluating and addressing CRP, zinc, iron, vitamin D and gut microbial dysbiosis would be an objective approach towards remediation of biological factors that may be contributing to depression for an individual. In this current environment it is prudent to address all determinants of inflammation and mental health.


Alper E., & Ceylan M., (2015) The Gut-Brain Axis: The Missing Link in Depression. Clin Psychopharmacol Neurosci. doi: 10.9758/cpn.2015.13.3.239

Barnes, J., Mondelli, V. & Pariante, C. Genetic Contributions of Inflammation to Depression. Neuropsychopharmacol 42, 81–98 (2017).

Czeisler, Mark, et all. Mental Health, Substance Use, and Suicidal Ideation During the COVID-19 Pandemic — United States, June 24–30, 2020 Weekly / August 14, 2020 / 69(32);1049–1057

Leonard, Brian E. “The concept of depression as a dysfunction of the immune system.” Current immunology reviews vol. 6,3 (2010): 205-212. doi:10.2174/157339510791823835

Raison, C. & Miller, A. Is Depression an Inflammatory Disorder? Curr Psychiatry Rep. 2011 Dec; 13(6): 467–475. doi: 10.1007/s11920-011-0232-0

Laboratory, Endocrine and Neurotransmitter Symposium (LENS)

February 12-14, 2021

Virtual Only

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Gain additional clinical insight and treatment considerations to evaluate some of the most prevalent and challenging conditions that patients present with, including depression, anxiety, altered mental focus and stamina, sexual dysfunction, sleep disturbances, addictions and dependencies, weight management, and chronic disease.

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Hormone Testing Options Compared: Saliva, Serum, Urine

By: Lylen Ferris, ND

January 6, 2021

Examine the pros and cons of testing hormones in various mediums: serum, urine and saliva.

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