Managing Depression as an Inflammatory Condition

Managing Depression as an Inflammatory Condition

Lylen Ferris, ND | March 17, 2021
Patients with major depression have been found to exhibit increased peripheral blood inflammatory biomarkers, including inflammatory cytokines. Cytokines have been shown to access the brain and interact with virtually every pathophysiologic domain known to be involved in depression, including neurotransmitter synthesis and metabolism, neuroendocrine function, and neural plasticity.

A 2014 study examined 50 non medicated patients with major depressive disorder (MDD). Before treatment, the inflammatory markers IL-1β, IL-5, IL-6, IL-7, IL-8, IL-10, and IFNγ were significantly elevated in depressed patients at baseline compared to healthy controls. After 12 weeks of treatment, the plasma levels of these seven cytokines had decreased significantly compared to baseline and did not differ from those in the healthy controls. Researchers concluded, “Recovery from depression was associated with reduction to normal levels of the majority of the measured cytokines. These results strongly support the notion that a complex network of cytokines is involved in the pathophysiology of MDD.”

Once cytokine signals reach the brain, they have the capacity to influence the synthesis, release, and reuptake of neurotransmitters like serotonin, dopamine, glutamate, and norepinephrine. Testing the neurotransmitter imbalance driven by these inflammatory cytokines provides information on how to approach patient support. Once imbalances are identified via spot or 24-hour urinary neurotransmitter testing, therapies such as amino acids, nervine and apoptogenic herbs, and essential nutrients can be implemented as appropriate. However, the underlying inflammation must not be overlooked.

Identifying the source of inflammation is essential, but it can be daunting to know where to begin. Common drivers of inflammation are lifestyle related: Does the patient smoke? Are they physically active? Obese? What does their diet look like and are food sensitivities a possibility? Dental health is an often-overlooked etiology of inflammation, as many patients do not have dental insurance and are neglectful of this area of health. Periodontal disease and dental cares can be sources of inflammation.

Hormone imbalance is often a reflection of inflammation, and perhaps a driver of it, as insomnia promotes inflammation, but can also be the result of inflammatory conditions and pain. Stress drives inflammation. Stress and insomnia are typically reflected in the disordered release of cortisol. Additionally, inflammatory metabolic syndrome drives androgen imbalance and estrogen dominance in males and females alike.

Another common etiology of inflammation is gastrointestinal dysbiosis and digestive issues. The intestinal epithelial lining, together with factors secreted from it, forms a barrier that separates the host from the environment. In pathologic conditions, the permeability of the epithelial lining may be compromised allowing the passage of food particles, toxins, antigens, and bacteria in the lumen to enter the blood stream and drive inflammation. Assessing the heath of the microbiome as well as digestive and inflammatory markers can provide essential information on gastrointestinal health.

When it comes to sources of inflammation, the good news is that most of these factors are plastic, and potentially amenable to therapeutic and preventative interventions. Taking a thorough history and employing appropriate laboratory testing will provide the practitioner with insight as to where to focus anti-inflammatory efforts in the management of depression and other neuroendocrine imbalances.



Berk M, et al. So depression is an inflammatory disease, but where does the inflammation come from? BMC Med. 2013 Sep 12;11:200.

Dahl J et al. The plasma levels of various cytokines are increased during ongoing depression and are reduced to normal levels after recovery. Psychoneuroendocrinology. 2014 Jul;45:77-86.

Miller AH, et al. Inflammation and its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression. Biol Psychiatry. 2009 <May 1;65(9): 732-741.

Qinghui Mu, Jay Kirby, Christopher M. Reilly, Xin M. Luo. Leaky Gut As a Danger Signal for Autoimmune Diseases. Front Immunol. 2017;8:598.