Increased inflammation is associated with a host of issues in the body. Chronic inflammation leads to chronic disease. Does this also include a unique type of major depressive disorder?
Inflammation is our body’s innate cellular defensive and protective response to threat, and as such it is essential to our survival. But it seems that in the modern world, our inflammatory response has gone a bit haywire. Research from current hunter gatherer populations demonstrates that inflammation increases in response to illness, injury, or other threat, and then subsequently decreases, which would be considered a normal and adaptive response from our body’s immune system. On the other hand, in our modern, western society there exists a subset of individuals who seem to be impacted by chronic levels of elevated peripheral inflammatory biomarkers, either because their body is sensitized to threat, or because current lifestyle practices introduce a whole host of mildly threatening toxins for their immune system to cope with. There has been a lot of buzz in the medical community about the role of inflammation in depression, and intuitively it makes sense to us that these chronic and insidious processes would overlap with each other to keep some of us locked into feeling less-than-good.
So, let’s break down the following: 1. Who are the individuals who could benefit from screening for increased inflammatory biomarkers? 2. What solutions and treatments will be most effective for those who are found to have elevated levels of inflammation? 3. Should we consider giving everyone with depressive symptoms targeted anti-inflammatory support?
Who can benefit?
First, it’s important to point out that we’re not reductively defining depression as a condition of inflammation. We are saying there exists a subset of individuals who are suffering from depression who also have increased inflammatory biomarkers—so, their immune system is overactivated and they might benefit from different or adjunctive treatment modalities. Also of note: there seem to be some individuals who may not have “off the charts” inflammatory markers, but who are extra sensitive to even the slightest elevations in inflammation.
About one quarter to one third of individuals diagnosed with Major Depressive Disorder will also have chronic elevations of inflammatory biomarkers.(1) Research has demonstrated that in individuals with Major Depressive Disorder, the higher the inflammatory markers, the worse the depressive symptoms will be.(2) These biomarkers include plasma cytokines IL-6, TNF, and CRP – all varying markers of inflammation. CRP (C-Reactive Protein) is one of the easiest and most cost-effective markers to routinely measure. We would argue that it is worthwhile to obtain a CRP in every individual who is suffering from depressive symptoms. Inflammatory pathways interact with every system in our body and brain, and inflammation can certainly be a cause for treatment resistance.
What are the solutions?
Research has shown that CRP levels may predict an individual’s response to an anti-depressant. The correlation seems to be that as one’s CRP levels rise, one will become less responsive to an SSRI.(3) This is important to acknowledge, as SSRIs (selective serotonin reuptake inhibitors) are a first-line treatment for depression. The same research demonstrates that individuals with elevated CRP markers may derive greater benefit from a medication that is less serotonergic and interacts more with the catecholamine hormones dopamine and norepinephrine, such as bupropion.
As always, it’s important to state here that at YWP, we believe in a strong foundation of lifestyle, diet, and exercise support. The goal of these interventions is to decrease inflammation! So, all of our patients, regardless of CRP levels in the blood, receive this same initial treatment – food is our medicine, sleep resets and renews, and movement promotes healing, strength, and resilience.
Why not give everyone diagnosed with depression targeted anti-inflammatory support?
Again, every single patient of ours does receive some form of anti-inflammatory support via lifestyle medicine. This creates the groundwork of our efforts here at YWP, which are centered around your daily foundation: food, sleep, exercise/movement. You might be asking, should we just give every person targeted anti-inflammatory support, in the form of prescriptions or even over-the-counter anti-inflammatory medications or supplements? The answer is surprisingly NO! When you look carefully at the research, it demonstrates that individuals with depression who also have elevated CRP levels benefit from additional anti-inflammatory support and even different treatment modalities, such as catecholamine-based antidepressant therapy. On the other hand, when individuals with depression who did not have elevated CRP levels were given infliximab (a potent anti-inflammatory) and even omega-3 fatty acids as adjunctive therapy, their depressive symptoms actually worsened.(4) These findings are surprising and not well understood at this point, although they may explain why some more recent research on the benefits of Omega-3’s in depression appears to be equivocal (5)—we could be treating two (or more) different kinds of depression without realizing it. The fact is, at YWP we treat individuals, not symptoms, and everyone has a unique process going on internally. The more we can understand about that “hidden” internal process, the more we can customize effective treatments.
Here at YWP, first and foremost we recognize the profound impact inflammation has on our bodies. We recognize that subacute and chronic inflammation is at an all time high due to chronic stress, toxic exposures, sleep disruptions, infections, injury, and traumatic life experiences, to name a few. The road to wellness is all about containing and reducing these inflammatory inputs, which is no small task! If you find you could use a little help on your journey, we’ll be here.
1. Raison, C.L., Miller, A.H. Is Depression an Inflammatory Disorder?. Curr Psychiatry Rep 13, 467–475 (2011).
2. Krishnadas, R., & Cavanagh, J. (2012). Depression: an inflammatory illness?. Journal of Neurology, Neurosurgery & Psychiatry, 83(5), 495-502.
3. Uher, Rudolf, et al. "An inflammatory biomarker as a differential predictor of outcome of depression treatment with escitalopram and nortriptyline." American Journal of Psychiatry 171.12 (2014): 1278-1286.
4. Raison, C. L., Rutherford, R. E., Woolwine, B. J., Shuo, C., Schettler, P., Drake, D. F., ... & Miller, A. H. (2013). A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA psychiatry, 70(1), 31-41.
5. Deane, K., Jimoh O., Biswas, P., O”Brien, et al., Omega-3 and polyunsaturated fat for prevention of depression and anxiety symptoms: Systematic review and meta-analysis of randomized trials. The British Journal of Psychiatry, 218 (3), 135-142. Doi:10.1192/bjp.2019.234