Inflammatory Depression Getting You Down?

The number one cause of depression in the USA is inflammation, also referred to as depression of chronic disease. There are both psychological and biochemical reasons why this is the case. I am going to outline a few reasons why you might not have a choice in developing a mood disorder like depression when chronic inflammation is present.

Depression in Chronic Disease

The odds are not in your favor if you suffer from a chronic disease. Check out incidence rates of major depression in a selection of diseases:

  • 1 in 5 persons with cardiovascular disease experiences MDD

  • Diabetes diagnosis doubles your odds of having depression

  • Up to 70% of patients with autoimmune diseases, such as rheumatoid arthritis, Hashimoto’s disease, or systemic lupus erythematous experience depression

  • Several studies show that 15% to 25% of cancer patients experience depression, compared with 9% in the general population; a doubling to tripling in rates!

Blame Inflammation

Inflammation is what makes us feel old and is often that wrench in your gear box that prevents you from moving forward. When your immune system is active, you produce large quantities of inflammatory molecules called cytokines. Pro-inflammatory cytokines stimulate the immune and nervous systems to mobilize them against some threat. Unfortunately, many threats are life-long (such as auto-immune diseases, diabetes, cardiovascular disease, herpes, etc.), undetected (chronic infections like tooth decay, mold exposure, Lyme disease, Small Intestinal Bacterial Overgrowth, etc), or ignored (food sensitivities, food allergies, poor diets, alcohol abuse, smoking, etc.) or part of the agin process (such as arthritis or degenerative joints). Pro-inflammatory cytokines will reduce the production of many of the brain chemicals, neurotransmitters, needed for a healthy nervous system and normal mood.

The Tryptophan Steal

Serotonin is one of the main neurotransmitters that helps regulate your overall mood. Most blockbuster antidepressant drugs (Prozac, Lexapro, Cymbalta, Effexor, Remeron and many more) are designed to reduce the breakdown of serotonin in an effort to raise a person’s mood. Psychiatry and conversional medicine has fully embraced this approach serotonin boosting to address depression, anxiety, panic disorders, sleep issues and even menopausal symptoms.

We all have an enzyme call indoleamine 2,3-dioxygenase (IDO) that increases in concentration in the presence of inflammation (pro-inflammatory cytokines) and causes what has been nicely described as the “Tryptophan Steal”. Normally the amino acid precursor to serotonin, tryptophan, is converted to 5-hydroxytryptophan (5-HTP) and then to serotonin. But inflammation increases IDO and instead of being directed toward serotonin production, tryptophan is directed into an altered pathway. This stealing of tryptophan results in less serotonin available for usage and storage. The tryptophan steal also results in more oxidative stress and stress to your brain.

Double Threat

In addition to IDO, you also require the enzyme tetrahydrobiopterin (BH4) in order to synthesize most of your neurotransmitters. Inflammation (pro-inflammatory cytokines) will eventually reduce BH4 production and thereby reducing the effected neurotransmitters further. This will result in further reduction of serotonin levels in addition to your energy and metabolism brain chemicals dopamine, epinephrine, norepinephrine, and phenylethlamine (PEA). This is why many people begin taking SSRI medications but eventually need to be switched to a SNRI drug class. This is why chronic inflammation significantly increases your odds of developing brain imbalances manifesting as fatigue, brain fog, anxiety, insomnia and depression.


Chronic inflammation can come from a variety of sources and its effect on neurotransmitter synthesis leads is the main cause of depression. Prescriptive medications are effective at increasing circulating levels, but do not increase overall levels of neurotransmitters. Long-term usage of antidepressants often occurs but they tend to work less in time, result in more side effects, and rarely addresses the the root causes behind not having enough serotonin in the first place. Most antidepressants result in further depleted neurotransmitter stores and less drug efficacy. If you are using an antidepressant, the next time you see your prescribing doctor please ask them to assess and address your inflammatory status and include strategies to increase your overall levels of neurotransmitters. If you suffer from depression and have not addressed inflammatory or immune causes behind it, you should start looking.

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