Treating systemic inflammation as depression therapy

Doctors at Emory University School of Medicine have made a connection between inflammation and depression:

  • “About one third of people with depression have high levels of inflammation markers in their blood. New research indicates that persistent inflammation affects the brain in ways that are connected with stubborn symptoms of depression, such as anhedonia, the inability to experience pleasure.”1

German researchers have made a connection between inflammation, depression and newly diagnosed diabetic patients.

“Depressive disorders represent a frequent comorbidity of both type 1 and type 2 diabetes. Inflammation-related processes have been implicated in the development of both diabetes and depression.”2

We are going to take a look at a fascinating paper that appeared in the journal Nature. The goal of the paper was to explain the role of inflammation in depression and how inflammation may prevent treatments from working.

Here is the abstract:

“Crosstalk between inflammatory pathways and neurocircuits in the brain can lead to behavioural responses, such as avoidance and alarm, that are likely to have provided early humans with an evolutionary advantage in their interactions with pathogens and predators.

However, in modern times, such interactions between inflammation and the brain appear to drive the development of depression and may contribute to non-responsiveness to current antidepressant therapies.”3

What does this mean for the patient with depression? It means there is an understanding that if we treat inflammation at the nervous system pathways  we can successfully treat depression.

The paper being explored in this article confirms what other investigators are confirming. That is the strong suspicion that the onset of depression may involve low-grade inflammation and endothelial dysfunction (damage and diseases of the inner lining of the blood vessels) as a causative factor.4

In highlights the Nature paper suggests:

  • The relationship between inflammatory pathways and the brain may drive depression and contribute to non-response to antidepressant medication.3
  • Increased levels of inflammatory cytokines ( i.e., growth factors that exert influences of other cells telling them what to do – signalling pathways) as well as activation of different immune cell subsets has been detected in the brain and peripheral blood of a subgroup of patients with depression. C-reactive protein (CRP), tumour necrosis factor, interleukin-1β (IL-1β) and IL-6 appear to be the most reliably elevated inflammatory markers in the peripheral blood of subjects with depression.3

Most are familiar with CRP (C-reactive protein) a molecule produced in the body that is used as a non-specific marker of inflammation. This molecule can be measured in the blood and, although it doesn’t identify the source of inflammation, (infection, injury or virus), its levels rise in response to inflammation in the body. Many chronic conditions are associated with the inflammatory response to injury. There are practitioners and researchers who are beginning to see chronic inflammation as a single disease 3

Here is an important factor in the inflammatory response that we have discussed before – the Gut – Brain connection. See Probiotics for psychiatric illness | New research

  • Inflammation by stress-induced, non-pathogenic stimuli (not a disease), including damage-associated molecular patterns as well as microbial-associated molecular patterns elaborated from the gut microbiome, may drive peripheral inflammatory responses, which are then transmitted to the brain by trafficking of activated monocytes. In very simple terms the bad bacteria in the gut is causing inflammation which is causing depression.3
  • Inflammation impacts several neurotransmitter systems in the brain, including serotonin, dopamine and glutamate pathways, as well as the kynurenine pathway, which generates the neurotoxic metabolite quinolinic acid.3

A point of explanation, increased levels of quinolinic acid has been linked to depression, autism, and in conflicting evidence seizures.

The findings of this and other research bolster the case that the high-inflammation form of depression is distinct, and are guiding researchers’ plans to test treatments tailored for it. 1

At the Magaziner Center for Wellness, we thoroughly assess each patient’s physical state and treat any triggers of depression without the use of medication. To begin, we look at inflammatory factors such as food sensitivities and allergies

If such sensitivities are detected, we work with the patient to modify his/her diet and environment to eliminate the element’s negative impact with includes modifying the inflammatory response.

We also look at their exposure to mold and other environmental irritants, such as building materials and household chemicals, which often harm the nervous system and impact mood and impact inflammation.

General guidelines recently suggested by Lauren Whitt, Ph.D from the University of Alabama at Birmingham offered suggestions on fighting inflammation with food. These foods can accelerate the anti-inflammatory response:

• Citrus fruits – Vitamin C and Vitamin E as essential antioxidants
• Dark, leafy greens – High in Vitamin K
• Tomatoes – The fruit’s red pigment, lycopene, is a potent antioxidant
• Wild-caught salmon – Contains a rich concentration of omega-3 fatty acids

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1  FelgerJC, et al. Inflammation is associated with decreased functional connectivity within corticostriatal reward circuitry in depression Molecular Psychiatry advance online publication 10 November 2015; doi: 10.1038/mp.2015.168

2 Herder C, Fürstos JF, Nowotny B, et al. Associations between inflammation-related biomarkers and depressive symptoms in individuals with recently diagnosed type 1 and type 2 diabetes. Brain Behav Immun. 2017 Mar;61:137-145. doi: 10.1016/j.bbi.2016.12.025. Epub 2016 Dec 29.

3 Miller AH, Raison CL Nature Reviews Immunology 16, 22–34 (2016) doi:10.1038/nri.2015.5

4 van Dooren FE, Schram MT, Schalkwijk CG, Stehouwer CD, Henry RM, Dagnelie PC, Schaper NC, Associations of low grade inflammation and endothelial dysfunction with depression – The Maastricht Study. Brain Behav Immun. 2016 Mar 9. pii: S0889-1591(16)30049-6. doi: 10.1016/j.bbi.2016.03.004. [Epub ahead of print]