Why inflammation is depressing!

A recent quote in the Journal of the American Medical Association said the following: “Psychiatic and neurodevelopmental disorders are being thought of more and more as systemic illnesses in which inflammation is involved.” (1) For a long time mental health concerns were treated as though they only involved the brain, that the rest of the body was separate and irrelevant. But this is changing; balance within the rest of the body is being thought of more and more as relevant.  One aspect of balance that seems to be of interest is inflammation. 

In a previous blog post I shared some of the current understanding about the role of dietary choices in the development and progression of mental illness.  This is the main area of focus for my research work.  One topic that I did not explore in the previous post, as it deserves its own focus, is the role of inflammation in mental health, and how diet can influence these levels. 

Let’s look at what the research shows.  Patients with depression higher levels of inflammation molecules in their body and in their brain and lower levels of anti-inflammatory molecules (2).  In animals, increasing levels of inflammation leads to lack of interest, deceased activity, altered sleep and eating behaviours – all symptoms of depression.  Administering anti-inflammatory molecules to these experimental animals blocks these effects. In humans, studies have found that increasing levels of inflammation can lead to increased anxiety, irritability, hyper-arousal and mania symptoms (3). 

Why does this happen? Proposed explanations for this phenomenon cite evolutionary benefits.  If an animal is injured or infected (two major causes of inflammation), it’s advantageous for their activity to be inhibited (increased sleep, decreased interest and activity) so that resources can be used for repair and recovery.  And if the animal is more vulnerable as a result of the injury or illness, it makes sense that it would be hyper-vigilant (a state similar to anxiety) against further harm. 

Clinically, studies have shown that patients with higher levels of inflammation are less responsive to anti-depressants (4) and when patients respond to anti-depressant medications and therapy, there is an associated decrease in inflammation. 

If inflammation impacts these emotional and behavioral states, how does it happen? It turns out that high levels of inflammation decreased the production of dopamine, a brain chemical important for mood.  They also speed up the breakdown of serotonin resulting in lower levels of another important mood-supporting brain chemical.  It also affects the production of serotonin in a negative way.  Under normal conditions, the amino acid tryptophan is used as a building block to make serotonin (Remember this from the previous article? This is why including protein in your diet is so important!) But when there are high levels of inflammation or stress in the body, the tryptophan is not converted to serotonin but to kynureinine, a molecule that is toxic to nerve cells (5).   

There are many ways to influence inflammation levels in the body.  Exercise is a potent anti-inflammatory agent while obesity, insomnia, physical inactivity, chronic stress and the standard North American diet are potent inducers of inflammation (6,7).  One important diet component that influences the levels of inflammation in the body is dietary fat.  Some fats have anti-inflammatory effect – these include omega 3 and omega 9.  And some have PRO-inflammatory effects (they increase inflammation in the body!) – these include omega 6 fats and trans fats.  The historical human diet contained a ratio of omega-3 to omega-6 of about 1 to 2.  That means that for every 1 gram of omega 3 fats, people were also getting 2 grams of omega-6 fats.  The current standard north American diet? It has a ratio of 1 to 20! That means that for every 1 gram of anti-inflammatory omega-3’s, people are getting 20 grams of pro-inflammatory omega 6’s (8).  Yikes! Omega-3 fatty acids are found in fish, flax, hemp and walnuts while omega-6 fats are found in the vegetable oils (corn, cotton-seed, peanut etc).  Egg, chicken and beef from animals fed an enrichhed or grass-based diet naturally contain omega-3’s but when conventionally produced the levels of omega-3s are extremely low. 

The evidence is mounting that inflammation is an important factor in mental illness. Diet and lifestyle factors can help improve this balance - talk to your Naturopathic Doctor for a personalized recommendation. 


1. Friedrich MJ. Research on Psychiatric Disorders Targets Inflammation. JAMA. 2014; 312(5):474-6.

2. HUANG TL, LEE CT. T‐helper 1/T‐helper 2 cytokine imbalance and clinical phenotypes of acute‐phase major depression. Psychiatry and clinical neurosciences. 2007 Aug 1;61(4):415-20.

3. Müller N, Myint AM, Schwarz MJ. The impact of neuroimmune dysregulation on neuroprotection and neurotoxicity in psychiatric disorders-relation to drug treatment. Dialogues in clinical neuroscience. 2009 Sep;11(3):319.

4. Mendlewicz J, Kriwin P, Oswald P, Souery D, Alboni S, Brunello N. Shortened onset of action of antidepressants in major depression using acetylsalicylic acid augmentation: a pilot open-label study. International clinical psychopharmacology. 2006 Jul 1;21(4):227-31.

5. Oxenkrug, GF. Tryptophan–Kynurenine Metabolism as a Common Mediator of Genetic and Environmental Impacts in Major Depressive Disorder: The Serotonin Hypothesis Revisited 40 Years Later. The Israel Journal of Psychiatry and Related Sciences. 2010; 47(1), 56–63.

6. Lakka TA, Lakka HM. Effect of exercise training on plasma levels of C-reactive protein in healthy adults: the HERITAGE Family Study. European Heart Journal. 2005;26(19):2018–2025.

7. Vgontzas AN. Chronic insomnia is associated with a shift of interleukin-6 and tumor necrosis factor secretion from nighttime to daytime. Metabolism. 2002;51(7): 887-92.

8. Simopoulos AP. The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomedicine & Pharmacotherapy. 2002; 56(8):365-379.