“In the lives of the saddest of us, there are days like this, when we feel as if we could take the great world in our arms and kiss it. Then come the gloomy hours, when the fire will neither burn on our hearts nor in our hearts; and all without and within is dismal, cold, and dark.” ~Henry Wadsworth Longfellow


Dismal is definitely an appropriate adjective for depression, but lately we’ve begun using a different descriptor: misunderstood. For the last several decades, healthcare professionals have generally attributed depression to simply a chemical imbalance. But, the times they are a changin’. Because the current bucket of solutions is insufficient, we’re continually looking for new answers. Especially, considering the fact that current antidepressant elixirs all carry varying degrees (1) of success. Providers and patients are getting tired of switching doses with the rapidity of a texting millennial. They want a more lasting solution.

Thankfully, we may have found at least part of the answer. While rhetoric about delicate balancing acts between serotonin and dopamine, two neurotransmitters that occur naturally in your brain, is still alive and kicking, there’s a new twist on an old twist in this the story.

This new twist is as surprising (and yet inevitable) as the next Trumpian tweet. In the case of depression, the culprit is the reoccurring villain in this tale of modern disabilities and diseases: chronic inflammation. While the association between depression and modulation of the immune system has long been identified; it turns out that chronic inflammation may actually cause an imbalance in the neurochemicals associated with depression(2).

This correlates with other evidence that suggests that conditions like obesity are the result of chronic inflammation and gut microbiome alterations. In the case of obesity, to a much larger degree than causation related to simple calories in versus calories out; the standard model and explanation for decades. This new hypothesis links depression not simply to an attitudinal or emotional choice, but a physical causation. That’s good to know, especially because the traditional pharmaceutical protocol sometimes does serious damage (3) The old adage of medicine applies to their use here; “The poison is in the dose.”

This recent research means that some of us may be able to avoid hours beached upon therapy couches or spending countless dollars on antidepressants that aim to treat symptoms, not the cause (3). The day may be arriving soon that patients no longer have to move between brands and dosages like the walking dead moving pharmacy to pharmacy. We’re finally starting to move away from placing great effort on treating merely depressive symptoms, and beginning to home in with drone-like precision on the real culprit.

But we’re not there yet.

What exactly precipitates this chronic inflammation?

Firstly, we must distinguish chronic continuous inflammation from an acute inflammatory response. For example, suppose you experience an injury; a trauma like a sprained ankle or tissue damage from toxins, viruses, or bacteria. These will cause an immune mediated response to protect your body (4), which serves a valuable purpose under such circumstances.

What happens when you get those immune responses? The body’s receptors are the first to notice the threat of an injury or invasion. They call nearby blood vessels, which dilate, and leukocytes (6) (white blood cells) rush to the compromised area like a bunch of fangirls to the stage of a One Direction concert.

The resulting increased blood flow (7) is responsible for the warmth, swelling, and redness we know as erythema associated with acute inflammation. As helpful and necessary as this may be, when it goes unchecked; those screaming fangirls can quickly become a concert maelstrom.

Even when your immune system is acting normally, common colds or other pathogen-caused illnesses cause your body to focus resources at fighting the bacteria or virus (8). The “down” feeling you may have during a cold or flu may be attributable to all that extra, but necessary, immune response. We are built for such life stressors with our flight or fight response. All these types of singular events flip our immune response into hyperdrive.

And just like a hyperdrive unit; an accelerated immune response is meant for a short fast flight or fight. When permanently left on, even in a sub-acute fashion, resources are depleted, and untoward effects emerge. The result can become widespread, promoting inflammation throughout the body. Symptoms associated with depression, such as unhappiness, fatigue (9), and hopelessness, can all be associated with this rampant inflammation.

It seems like a big jump to assume that this generally healthy inflammation can cause depression, but another medical therapy may give some insight into the mechanism. Collected data from vaccine clinics suggest it. They’ve reported (5) slight waves of depression in patients following inoculations. Those cocktail shots of virus and bacteria-laced vaccines almost always lead to some kind of immune response, so a possible explanation for the sudden mood shift would be contemporal tissue inflammation. As a caveat, polio no doubt leads to much more permanent mood depression.

Likewise, when patients take medications that have pro-inflammatory effects, depressive symptoms tend to appear. Whether this connection is causal or correlative, cannot be determined at present, but make no mistake; it is present.

And among the power players all revved up with such drugs are the cytokines. These proteins are responsible for controlling your immune system, and heightened levels of them can indicate inflammation in the brain. People with depression show higher levels of cytokines in their systems.


No such thing in a quantum reality that observes the interconnectedness of all things.

Not only are depressive symptoms noted in patients with chronic inflammation (11), but gut microbiome abnormalities associated with chronic, continuous, systemic inflammation correlate and can presage the development of various neurological and psychiatric states. What is clear is that the previously held belief that there is a distinct separation between the brain and the immune system is not accurate. For patients diagnosed with depression, there may be a whole new realm of treatment options ahead that may be more effective, holistic, and with fewer side effects. Such anti-inflammatory treatment protocols (10) are yielding benefits and insights in some unexpected ways. Such fresh approaches are birthing new areas of cross disciplinary study like psycho-neuro-immunobiology.

Now that we are aware that the cause of depression may be a physiological abnormality, at least partly rooted in chronic, continuous inflammation, perhaps the negative stigma of mental or emotional weakness surrounding it can be minimized. Maybe society will finally stop putting mental health into the corner and give it the understanding it deserves. Given that depression itself is as potent a risk factor for the development of cardiovascular disease (a known consequence of chronic, continuous inflammation) as any cholesterol level; perhaps we can start connecting dots instead of pointing fingers.

A physiological basis, giving depression a tangible cause, may also encourage more people to seek treatment. They won’t be worried about the humiliation and terrifying, potentially harmful pills they imagine having to pop for the rest of their lives. Instead, they’ll see depression on par with cardiovascular disease, diabetes, and other such maladies.

That’s why many doctors and researchers are starting to look at inflammation control as the next step to treatment. And many efficacious outcomes in this direction can be achieved with lifestyle changes; diet, exercise, and other cost effective, non-pharmacological approaches. Studies continue to provide grounded evidence that such  protocols may be effective. A treatment that empowers those suffering from depression is certainly an advance from one that disenfranchises.















14. Fenster, M. S. (2014). The Fallacy of The Calorie: Why the Modern Western Diet is Killing Us and How to Stop It. New York, NY: Koehler Books.

15. Fenster, M.S. (2018 in press). Food Shaman: The Art of Quantum Food. New York, NY: Post Hill Press.

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