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Is Depression a Disease or a Symptom of Inflammation?


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The idea that depression and other mental health conditions are caused by an imbalance of chemicals (particularly serotonin and norepinephrine) in the brain is so deeply ingrained in our collective psyche that it seems almost sacrilegious to question it. 

A depressed person
Depression and inflammation are linked. Find out how. iStock.com/AntonioGuillem

Of course, Big Pharma has played a role in perpetuating this idea. Antidepressant drugs, which are based on the chemical imbalance theory, represent a $10 billion dollar market in the U.S. alone. According to the CDC, 11 percent of Americans over 12 years old take antidepressants, and they are the second-most prescribed medications (after cholesterol-lowering drugs). Doctors wrote a staggering 254 million prescriptions for antidepressants in 2010. (1)

Research suggests that depression may be primarily caused by inflammation. Check out this article to find out more about the depression–inflammation connection. #MentalHealth

Yet as popular as this theory has become, it is riddled with problems. For example: 

  • Reducing levels of norepinephrine, serotonin, and dopamine does not produce depression in humans, even though it appears to do so in animals.
  • Although some depressed patients have low levels of serotonin and norepinephrine, the majority do not. Several studies indicate that only 25 percent of depressed patients have low levels of these neurotransmitters.
  • Some depressed patients have abnormally high levels of serotonin and norepinephrine, and some patients with no history of depression have low levels of them. (2)

What if depression isn’t caused by a “chemical imbalance” after all? More specifically, what if depression itself is not a disease, but a symptom of an underlying problem? 

That is exactly what the most recent research on depression is telling us. A new theory called the “Immune Cytokine Model of Depression” holds that depression is not a disease itself, but instead a “multifaceted sign of chronic immune system activation.” (3)

To put it plainly: depression may be a symptom of chronic inflammation.

The Connection between Depression and Inflammation

A large body of research now suggests that depression is associated with a low-grade, chronic inflammatory response and is accompanied by increased oxidative stress. 

In an excellent review paper by Berk et al, the authors presented several lines of evidence supporting the connection between depression and inflammation: (4)

  • Depression is often present in acute, inflammatory illnesses. (5)
  • Higher levels of inflammation increase the risk of developing depression. (6)
  • Administering endotoxins that provoke inflammation to healthy people triggers classic depressive symptoms. (7)
  • One-quarter of patients who take interferon, a medication used to treat hepatitis C that causes significant inflammation, develop major depression. (8)
  • Remission of clinical depression is often associated with a normalization of inflammatory markers. (9)

During an inflammatory reaction, chemicals called “cytokines” are produced. These include tumor necrosis factor (TNF)α, interleukin (IL)-1, interferon (IFN)ɣ, and interleukin (IL)-10, among others. Researchers discovered in the early 1980s that inflammatory cytokines produce a wide variety of psychiatric and neurological symptoms which perfectly mirror the defining characteristics of depression. (10)

Interestingly enough, antidepressants (particularly SSRIs) have been shown to reduce the production of pro-inflammatory cytokines like TNF-α, IL-1, interferon IFN-ɣ and increase the production of anti-inflammatory cytokines like IL-10. (11, 12) They also change the gene expression of some immune cells that are involved in inflammatory processes. This suggests that SSRIs are anti-inflammatory, which would explain their mechanism of action if inflammation is a primary driver of depression.

The research on this topic is robust, and the connection between depression and inflammation is now well-established. But if depression is primarily caused by inflammation, the obvious question that arises is, “What is causing the inflammation?”

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Nine Common Causes of Inflammation and Depression

If you’ve been following my blog for any length of time, you know that inflammation is at the root of nearly all modern disease, including diabetes, Alzheimer’s, cardiovascular disease, autoimmune disease, allergies, asthma, and arthritis. So perhaps it shouldn’t come as much of a surprise that depression is also caused by inflammation

The downside of this connection is that our modern diet and lifestyle are full of factors that provoke inflammation—and thus cause disease. The upside is that if we address these factors and reduce inflammation, we can prevent and even reverse the chronic, inflammatory diseases that have become such a fixture of industrial civilization.

According to the authors of the Berk et al review paper I referenced above, the following are the most common causes of inflammation that are associated with depression. 

1. Diet

There are several problems with the modern diet. It is high in foods that provoke inflammation, such as refined flour, excess sugar, oxidized (rancid) fats, trans fats, and a wide range of chemicals and preservatives. And it is low in foods that reduce inflammation, like long-chain omega-3 fats, fermented foods, and fermentable fiber. Numerous studies have associated the Western diet with major depressive disorder. (13)

2. Obesity

One of the most harmful consequences of the modern diet has been the dramatic increase in obesity. Obesity is an inflammatory state. Studies have shown higher levels of inflammatory cytokines in obese people, and weight loss is associated with a decrease in those cytokines. (14) Obesity is closely linked with depression, and while that relationship is likely multi-factorial and complex, inflammation appears to play a significant role. (15)

3. Gut Health

Disruptions in the gut microbiome and leaky gut (i.e. intestinal permeability) have both been shown to contribute to inflammation and correlate with depression. For example, a leaky gut permits endotoxins called lipopolysaccharide (LPS) to escape the gut and enter the bloodstream, where they provoke the release of inflammatory cytokines such as TNF-α, IL-1 and COX-2. (16) And numerous studies have linked unfavorable changes to the bacteria inhabiting our gut with major depressive disorder. (17

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4. Stress

Stress may be one of the most obvious causes of depression, but the link between stress and inflammation is less well-known. Research has shown that psychosocial stress stimulates the pro-inflammatory cytokine network, including increases in TNF-α and IL-1. (18) These increases in inflammatory cytokines are in turn closely related to depressive symptoms, as described above. 

5. Lack of Physical Activity

There’s a huge amount of evidence indicating that exercise is an effective treatment for depression—in many cases as effective or more so than antidepressant drugs. It has also been shown to prevent depression in healthy people with no pre-existing symptoms. (19) Interestingly enough, while exercise initially produces the same inflammatory cytokines that are associated with depression, that is quickly followed by induction of anti-inflammatory substances. (20) This is known as a hormetic effect, where an initial stressor provokes a compensatory response in the body that has positive, long-term consequences. 

6. Sleep Deprivation

Chronic sleep loss has been shown to increase inflammatory markers even in people that are otherwise healthy. (21) And although temporary sleep deprivation has been used to therapeutically improve depression, chronic sleep loss is a well-known contributing factor to developing depression in the first place. (22

7. Chronic Infection

Chronic infections produce ongoing inflammation, so it’s no surprise to see that depression is associated with Toxoplasma gondii, West Nile virus, Clostridium difficile, and other pathogens. (23, 24, 25

8. Dental Caries and Periodontal Disease

Dental caries and periodontal disease are another source of chronic inflammation, and thus a potential cause of depression. According to one large study of over 80,000 adults, researchers found that people with depression were more likely to have tooth loss even after controlling for several demographic and health factors. (26

9. Vitamin D Deficiency

Low levels of vitamin D are common in Western populations, and there is growing evidence linking vitamin D deficiency to depression. Vitamin D modulates immune responses to infection, including reducing inflammatory markers like TNF-α and IL-1 that are associated with depression. (27) Supplementation with vitamin D to normalize serum 25D levels has been shown to to reduce inflammatory markers in some, but not all cases. (28)

The Biggest Problem with the Chemical Imbalance Theory

The early 1980s discovery that inflammatory cytokines produce all of the characteristic signs and symptoms of depression should have made a big splash. For the first time ever, scientists had discovered a class of molecules that were tightly and consistently associated with depression, and, when administered to healthy volunteers, produced all of the symptoms necessary for the diagnosis of depression. 

Unfortunately, the “chemical imbalance” theory continues to be the dominant paradigm for understanding depression nearly 30 years after this profound discovery, despite the weak correlation between serotonin, norepinephrine, and dopamine and depressive symptoms. There are probably several reasons for this—and you’d be correct if you guessed that some of them are financial—but I’ll leave that discussion for another time.

The significance of this finding is huge—both for patients and clinicians. It shifts our focus from viewing depression as being a disease caused by a chemical imbalance, which often requires medication to correct, to being a symptom of a deeper, underlying problem. It also leads to entirely new avenues of treatment—many of them more effective and safer than antidepressant drugs.

Understanding the physical roots of depression can have a profound effect on people who are suffering from it. Although the stigma surrounding depression has decreased in recent years, many who are depressed still carry the burden of thinking that there’s something wrong with them, and the depression they experience is “their fault.” When my patients with depression learn that theres an underlying physiological cause of their symptoms, they often feel a tremendous sense of relief and empowerment. Whats more, when we address this underlying cause, their mood improves dramatically and they quickly realize that the self-judgment and shame they felt about being depressed was misplaced and unwarranted.  

I don’t mean to suggest that emotional and psychological factors don’t play an important role in depression. In many cases they do, and I’ve written on that topic before. However, the assumption in mainstream medicine that depression is exclusively caused by those factors is obviously not true, and too often these other potential underlying causes go unexplored. The doctor prescribes an antidepressant, the patient takes it, and thats the end of the discussion.

What to Do If You’re Suffering from Depression

With this in mind, what can you do if you’re suffering from depression? Follow these two steps:

1. Adopt an Anti-Inflammatory Diet and Lifestyle

This means eating a nutrient-dense, whole foods diet, getting enough sleep, managing stress, engaging in appropriate (not too little or too much) physical activity, and nourishing your gut. For more on how to do this, see my book, The Paleo Cure.

2. Investigate Other Underlying Causes of Inflammation

On your own or with the help of a good Functional Medicine practitioner, explore other possible causes of inflammation that could be contributing to depression. These include gut issues (SIBO, leaky gut, dysbiosis, infections, etc.), chronic infections (viral, bacterial, fungal), low vitamin D levels, dental caries and periodontal disease, exposure to heavy metals and mold or other biotoxins, obstructive sleep apnea, and more.

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Join the conversation

  1. I have noticed for a long time that when I leave sugar and white flour out of my diet, everything regarding my physical and mental health improves. I drop weight, feel happier, move better and generally enjoy life a lot more. It’s not an exaggeration to say it’s the difference between life and a living death. Regarding depression, I have suffered from in on and off and, now that I think about it, it may be linked to high-sugar eras in my life. This article is life-saving. Thanks so much

  2. This is an excellent article. I had been thinking about inflammation as the underlying cause of so many of our problems (I wrote about it here http://benboomed.wordpress.com/2014/08/08/inflammatory-speech/ ) but depression was not one of the things that had occurred to me. But what I really wanted to mention is that recently I have been experimenting with pycnogenol, which is supposed to be a pretty good anti-inflammatory (it is derived from the bark of pine trees, BTW) and to my surprise, for once I found that some of the hoopla seems to be justified. I am always a bit at a loss when something like this seems to help as I really don’t believe in magic bullets, but having discovered that magnesium made a HUGE difference in my life I am now on the lookout for other possible supplements that actually work. Most of them that I have tried have made no difference, but I believe that pycnogenol is worth following up on.

    • I suggest Wobenzym N for chronic inflammation. I take 3-4 tablets on waking and don’t eat for at least 45 minutes afterward. I know it works for me because I recently ran out and didn’t take it for a week. My debilitating arthritic hip pain and stiffness returned and I could not walk without looking injured. This resolved within days after re-starting my daily Wobenym N. I’m also taking magnesium carbonate daily and I’ve been eating low carb, high fat for the past 6 months.

  3. I enjoyed the read about depression. I agree with the nutritional approaches to clear the “cloudy view’ of so called depression. Definitely medication is a non -starter and should be eliminated. Once the view is clear a more sensible observation can be engaged in to look a depression. These observation don’t follow the European viewpoint of no psyche to mental depression. Therefore the road out is the road through . Lots of work just to start ahead of us. Keep strong.

  4. Would low dose naltrexone be helpful for decreasing inflammation in people experiencing depression?

    • Yes, there is some evidence that LDN reduces central nervous system inflammation, which is one reason why it may be effective against depression. It also increases endorphin levels, which could also explain it’s effect.

      • There too is evidence that from benefiting from the ‘rebound effect’ by taking LDN which upregulates the body’s own natural supply of met enkephalin (known as OGF) which has demonstrated to be a potent anti inflammatory agent exerting beneficial effects on the immune system ties in nicely with your research and explanation of depression. Thank you!

  5. I wonder if this “research” and the people who then blog about it have ever experienced depression…

    It’s easy to comment from the side-lines…

    • During my 10-year struggle with chronic illness I experienced severe depression. Healing my illness—which was inflammatory—cured my depression, so I am speaking not only about what the research says, but from personal experience.

      • I too experienced a complete reversal of mild to moderate depression upon discovering (at almost 50) that the underlying cause of a variety of symptoms was celiac disease. I have the blood work correlating, for example, a change in D-25 status from 42 on a more Paleo diet to 26 when travelling and feeling awful, and back to 43 now that I’m finally completely gluten free. My definition of ‘awful’ includes not only digestive but inflammatory symptoms of joint pain, pre-diabetic level blood glucose/A1C readings (despite not being overweight), headaches, etc. My theory has been that the malabsorption (of fat soluble vitamins D, A, K2) caused by the intestinal damage of celiac resulted in inflammation, spiraling into more symptoms. Chris, I wholeheartedly agree with your assessment that depression is a symptom of inflammation which can, in turn, have multiple root causes. Looks like most roads still lead to the gut!

        • Rae, so true. Known since I was a child something was wrong. Took another 25 yrs. for a doctor to even bring up the subject of celiac. Lost faith in what most of them had to say. Started having heart palps about 3 yrs. ago. Tests showed a high level of blood calcium. Well, the endo scheduled me for hyper-parathyroid surgery. The surgeon insisted on further testing – which seems to be an epidemic where I live. No, it was “only” osteoporosis, everyone seems to be sporting their little throat scars……but wait, they do have very expensive meds available. I read up on them and said NO. Reading for the past 3 yrs. has helped amazingly well. That jerk endo never once recommended D3, magnesium. K-2, nor a slew of others – nor that celiac is known to prevent absorbtion of critical nutruients. Oh, and the magnesium puts me to sleep like a baby and my husband claims that I used to have a hair trigger temper and now I don’t.

      • Chris,
        Thank you for your candor regarding major depressive disorder. I’m 41 and struggle with Endometriosis, Fibromyalgia, interstitial Cystitus and IBS, plus major depression. I was diagnosed with IBS and anxiety at age 7. The other diagnosis followed in my early and mid-20’s. I have a Master’s Degree in Biology and Pathology received in ’99 so the clinical data has changed much over the years – also, as we say “Big Pharma,” has had an enormous impact on what and how information is studied and the results distributed. I’m preaching to the choir I realize. I guess my true question lies with this, I have bought whole-headedly, the Paleo diet/life-style, but still suffer major depression. I’m not on an SSRI or any other type of anti-depressant – having taken them in the past with no positive effect and sometimes extremely negative ones. Behavioral Cog. Therapy also has been of no long-term usefulness – other than the brief time I have a one on one session and am able to verbalize the negativity and severe abuse I endured as a child and in 2 other adult relationships. As I said, even then, the positive results are briefly felt.
        I do have VERY low D3 which I take a daily 5,000 IU dissolvable gel tab for and after many months have not noticed any help – though I need to check on my new D3 baseline on the dose, but the Dr seems to feel that unnecessary. Currently I take an opioid for my anxiety and PTSD and a strong narcotic for pain. I STRONGLY dislike being on any medication like this, but my Dr’s have yet to give me a reasonable alternative except for having a hysterectomy (!) which would be my 16th surgery and which would bring many many other physiological, not to mention neurological implications into play. I used to be a thin active healthy child. I want that back. I have too much life left to live, but I don’t want surgery and going cold-turkey off the opioid and narcotic frightens me and that’s the option my Dr gave me – no weaning schedule!? I guess, even with my own knowledge and the research I try to remain up-to-date on (not via Big Pharm.) I just don’t know where to start and the depression doesn’t help that, neither does having found myself in a position I cannot afford to eat and buy homeopathically. I know I’ve introduced many topics – any suggestions, especially with depression with weight gain appreciated. Also, I really want to explore how genetically predisposed we are to many of these things (knowing already how damaged our environment/ecosystem is) such as premie babies of mother’s who smoked, drank, ate poor diets and where peri-natally depressed themselves – any research you could point me to or any experience with generational illnesses?
        Thank you and thank you for your own tremendous documentation on Paleo/holistic health.

        • As someone has said, you need to take D3 with K2 MK7. they work together with calcium and a little vitamin A.

          15 surgeries is way too many. I could imagine you have been very damaged by the surgeries.

          Usually one can find natural remedies to avoid surgery but doctors stay ignorant of them. you need to exhaust alternative non surgery methods.

          What natural remedies have you tried for IBS, Endometriosis and IC ?

      • Thank you Kris, that’s one. Knowledge is good (as evidenced here by all the knowledgeable posts), but WISDOM, is precious.

      • Well it’s still not true for everyone.
        I keep having my body checked for inflammation and I don’t have any (through blood work)
        …and yet I still struggle with clinical depression (dysthymia).

        • I think inflammation is hard to measure. My CRP came in within the reference range, but, I don’t know if that is a very valuable measurement. Mark Sisson seems to think the reference range is too high.


          I was also fairly intrigued by the work of Dr. William Walsh, mentioned in the comments for Chris’ latest podcast on methylation. But, I was also intrigued by Dan Kalish’s work, and have lost my enthusiasm for his “mind mapping” approach. I have no first-hand experience with either approach.

          Here’s a link to The Bulletproof Executive’s interview of Dr. Walsh. I found it interesting, but, not making any recommendations.


          I hope you find a way to feel better, and I think I understand the frustration you might be feeling.

          • there is a supplement that brings CRP level down. One study showed it dropped CRP score by in participants by 50%. The supplement is called Provinal Omega 7 Concentrated Palmitoleic Acid. It seems to have a wide range of positive effect in people. It seems to work pretty quick within one month. Definitely something to look into.

    • Amen. Suffering with depression, who has the energy or clarity of mind to even read all this speculation! Just tell us what to do to stop the pain!

  6. I found the comment about magnesium and vit D interesting.
    So many people are Vit D deficient and I have always thought that there was more going on than just not getting enough sunshine. Also the magnesium deficiency is not from poor diet. I recently discovered that Aluminium toxicity blocks the absorption of magnesium. Many people have Aluminium toxicity because it is not only in aluminium cans, antiperspirants etc but it is in our water supply. I have bought a water filter to minimise the aluminium as well as many other heavy metals.

    • Agreed! A reverse osmosis filtration system (Many under $300) is one of the best health investments you can make. Also removes chlorine & fluoride right at the tap, unlike faucet mount systems. Nobody should be Drinking chlorine, fluoride, aluminum & other junk that is present even in “superior” rated city water supplies.

    • One of the worst place to get aluminum is in Baking Powder. I always buy the non aluminum kind.

  7. Hi
    I have Chronic Polymyalgia and Arthritis in many Joints. I’m Diabetic amongst other problems also. I found out I had very low Testosterone. Went on replacement therapy and it had a huge effect on the Polymyalgia and Diabetes and associated decades long intractable depression. I cannot say my problems disappeared but I was able to cope better than before. Testosterone has huge effects in men and women on many aspects of the systems in the body. Lack of it is like a car without fuel. I cannot get up the stairs without it.

  8. Hello Chris

    Very insightful article. I stumbled over the sentence with mold being a a cause of chronic inflammation. Do you have further information about that? Just recently we found out that we had water coming from the apartment above us behind the wooden ceiling in out bathroom. It was full of hidden mold – for an unknown period of time. Now I am a bit concerned about possible long term consequences.
    Any further insight highly appreciated!


    • Hi Mike,

      I will be writing an article on how mold and other biotoxins can lead to something called “chronic inflammatory response syndrome (CIRS)” soon.

      • This is really needed Chris. Although I read estimates that only 2-5% of American homes have toxic mold, the presence of non-toxic mold is much more common, and seems to cause a lot of people (including me) health issues. I assumed it was just an allergic reaction, but I’d like to know more about other effects it might have, and especially any ways you know to deal with the symptoms.

        And thanks for the great article, as always!

  9. I have thought for a long time that dental problems and periodontal disease is a co-symptom of general inflammation not a causal agent. I have no research evidence to back this up, but I haven’t seen research that contradicts that idea either. The gums seem to be the type of tissue that would become easily inflamed/infected during a general low-grade body-wide inflammatory response, similar to the gut and skin.

  10. Excellent article. It’s a pity though there is no mention of MAGNESIUM an anti inflammatory agent most people consuming processed foods fail to meet the current low Magnesium RDA.
    Magnesium enables the Vitamin D form Cholecalcferol convert to calcidiol and then to calcitriol its active hormonal form.
    Correcting magnesium deficiency also impacts of Vitamin d levels and effectiveness.

    • I’m a huge believer in magnesium supplements. After 10 years of constipation and 8 years of heart palpitations and chronic inflammation manifesting as arthritis I found out about magnesium. Within days of starting to take it things began to improve and now, four months later I have a new lease on life. (I had already changed my diet and exercised regularly, am not over weight, don’t smoke etc.)

      • Ardys, How much Magnesium did you take? I , too, suffer from constipation for 5 years or so. I heard advice to take Magnesium (500-1000) day and other source said Magnesium Citrate.

    • For me, symptoms of depression (five years ago) abated completely when I quit statin drugs and supplemented with magnesium (drinking mag water, per the affibers’ recipe, plus topical mag oil). My cholesterol levels are sky high, which may make my primary care physician nauseous but is clearly how my brain likes it.

      There is a chance, I suppose, that my self experimentation has had a placebo effect. I embrace it. Anyone with depression should be trying any non-harmful thing they can think of to fix the problem. If something helps, but it is only the placebo effect, fine. As I recall, for the SSRI drug trials the control groups experienced massive improvement in symptoms on a placebo, with the SSRIs only barely beating them (75% improved on SSRIs, 70% improved on placebo).

      I understand that doctors cannot prescribe placebos, which when the alternative is SSRIs seems a shame.

      If you have depressive symptoms, you need to get off of statins (at least as an experiment). Mag water (magnesium bicarbonate) is an outstanding way to supplement magnesium (easy, cheap (20 cents a day) and well absorbed). Mag oil (magnesium chloride (nigari) dissolved in water) applied topically is, in my non-expert opinion, another effective way to get magnesium.

  11. In M.E. there is evidence of autoimmune activity against serotonin. Some patients have elevated serotonin, and some have low serotonin. I find a low 50mg dose of 5-HTP helps a bit, but 100mg gives me a headache. So I don’t think I have low serotonin, just that some serotonin is either damaged, or not completing its job because receptor sites aren’t functioning like they should because of inflammation.

    • 5-HTP 50mg 3x daily has helped me tremendously! I also tried 100mg 1x daily and got nothing more than an upset stomach. I did read somewhere that 5HTP shouldn’t be taken for more than 12 weeks at a time. Does anyone know if this is accurate? No doubt that a healthy diet only brings more benefits.

    • Re Curcumin – anti-inflammatory action.
      Curcumin for the treatment of major depression: A randomised, double-blind, placebo controlled study used 500 mg twice daily or placebo for 8 weeks and concludes
      “Partial support is provided for the antidepressant effects of curcumin in people with major depressive disorder, evidenced by benefits occurring 4 to 8 weeks after treatment.”
      Other research shows Curcumin works more effectively when taken in conjunction with Vitamin C. Vitamin C also helps resolve depression.
      It also makes sense to ensure natural levels of all anti-inflammatory agents (Omega 3, Vitamin D3, Magnesium and Melatonin) are all restored.

      • Totally agree. The only thing to add is that Omega3’s are fragile & easily oxidized when in fish oil capsule form (from some forms of processing, heat in transportation, time sitting on a shelf…). So, Eating foods high in omega 3’s like Wild Caught salmon, mackerel… is best. I bet you know that, Edward, but I’m throwing this in because I only learned about importance of omega 3’s from Food sources in the last half year.

  12. This is an interesting idea and certainly relates to my experience. I dealt with chronic subclinical depression for over twenty years, sometimes severe enough to reach a clinical level. Lexapro helped a little, birth control pills helped even more, but not enough, and the positive effect faded over time. 1 1/2 years ago i started a paleo diet, and was amazed to find all my mood issues gone without a trace. NO depression at all anymore. I don’t get very stressed out anymore, and events that used to crush me roll right off. I can’t express how wonderful it is to feel NORMAL. I have not had this effect with any other treatment. As to the shame of depression, i really think this is another symptom. I was deeply ashamed, not of being depressed, but of myself and my infinite flaws that I could not stop brooding over. Those things simply don’t bother me much anymore, thanks to my much healthier brain. All thanks to paleo.

  13. The important thing aboit focusing on inflammation is to solve problems like leaky gut, root canal bacteria, gene problems that cause problems in the body, etc. These are issues for me, and the more I learn about these things, the better my depression gets. The rise in depression among the general population may be linked to all kinds of problems with our diets and health care () and environment. A Paleo diet low in carbs and sugar has helped me, and learning about MTHFR and other gene mutations has helped me, too. There’s a lot to learn. I wish the insurance companies would help with my expenses for supplements.

  14. I never experienced depression until the last year after my relationship with someone who had bipolar II. She was abusive towards me, so the stress was unlike I’ve ever experienced. I’ve managed my Crohn’s very well with GAPS, so I do everything you recommend.

    In my case, I think its the emotional and psychological factors, and my lack of a support network/friends that contributes to my depression. And the stress of being depressed and not supporting myself financially.

  15. I totally believe the ubtestinal track can have enormous help to leading to other problems. That’s where it starts. I suffer mild depress duo and take Effexor! I also suffer intestinal bloating and colitis. I agree

  16. Would you characterize SAD as a potentially inflammation-driven disorder? I suffer terribly from it.
    My CRP levels have been undetectable, although to be fair I don’t remember whether those were taken in winter, spring or fall (wasn’t summer).
    While light therapy (I bought the little one you recommended) helps and I exercise regularly with benefit for maybe 2 hours after, the most profound effect I’ve experienced has been an SSRI.

        • Marie, When possible, it is always better to get your Vit. D3 (really is a hormone) from the sun. Why? because the sun provides other factors that have a synergistic effect. There are also likely additional factors/ benefits provided by sun exposure that haven’t yet been discovered. I am 54, and yes, I still happily wear a bikini. Even if you normally don’t, it is worth getting one (or, something that allows Maximum skin exposure, like a rolled up tank top & shorts) & perhaps you have a back yard to lay out in. I do apply a nontoxic sunscreen to my face, neck & tops of hands to avoid wrinkles. (I like Tropical Sands all natural 30 spf lotion. it is sometimes on Amazon, or order from their website: http://www.mexitan.com. Really, any brand that uses a physical barrier- Zinc &/ or titanium dioxide- & is biodegradable is safe to use. It’s also reef-safe. There are other good brands like Badger, but they are more expensive. T.S. 30 spf Won’t turn you white; the 50 spf will). Anyway, don’t put sunscreen anywhere unless you are avoiding wrinkles, have a sunburn or need to cover precancerous skin areas. The whole idea is to get maximum skin exposed to the sun on both sides Without getting a sunburn. Try to do this every few days. Even minimal sun exposure is better than none. Your body will store Vitamin D, so “stock up” from the sun during warmer weather & supplement only when it is just too cold to lay outside.

          • Thank you for the suggestion, and I agree entirely. In the summer I have no issues and get as much sun as possible.
            But it’s *seasonal* affective disorder, and the sun simply doesn’t get night enough in the sky, nor would I be able to bring myself to stand exposed in 20 degree weather 🙂 The only option was supplementation.

    • Marie, I’ve read that there might be a hypothyroid connection with SAD, but I’m not sure if much research was done, or if that connection panned out. It could be something to look into . . my hypo symptoms get much worse in the winter. If it was just the light exposure, I would assume that the light box would alleviate the problem, but since it doesn’t, perhaps the temperature difference is a factor to consider?

      • Yes, I believe the temperature difference is a factor, thank you very much for the suggestion! 🙂 However, I don’t think it’s working through thyroid in my case.
        I’m under constant monitoring for ‘subclinical hypothyroidism,’ (thyroid hormones are just under where they should be) but I tried thyroid medication and all it did was speed up my metabolism enough to lose weight (that I can’t afford to lose). My hypothesis is that the cold triggers a bad nervous system reaction, though I’ve no science to support that that’s even possible.

    • Hi Catherine
      Tryptophan is catabolised through the Kynurenine Pathway in 2 ways, triggered by inflammation and IDO or Indoleamine 2,3, dioxigenase enzyme, which usually produces an agitated depression, due to excessive output of Quinolinic acid, which is an NMDA receptor agonist.
      The second pathway, through the same Kynurenine process, is through TDO or Tryptophan 2,3, Dioxygenase, which results in Kynurenic acid, producing a melancholic depression, due to the antagonistic nature of Kynurenic aci. Severe forms of Tryptophan degradation results in Schizophrenia.
      Hope this helpsw

  17. I wish to speculate a little – perhaps these fall into order??? Seeing that most people here have abundant biochemicall knowledge, I hope to provoke ideas: one area of obvious inflammation is injury. Does depression (a chronic state) parallel chronic inflammation in multiple sclerosis due to ‘injury’ (much like varicose veins … of brain vesicles)?
    I found advertising for ‘cleaning arteries’ using EDTA, fascinating. One recent focus was the stagnant brain-blood supply was compromised in folks with multiple sclerosis. Would EDTA help? It is known that people with ms have low D3 [arterial calcium and vitamin K2 levels (M-7 fraction) I do not know. Would the new vitamin D3 patches from http://www.rawfoodworld.com help here? They also have the K2 (M-7). Wouldn’t this assist with all nerve-tissue (like excess glucose) alteration (inflammation /depression)?

    • http://m.jnnp.bmj.com/content/early/2012/02/21/jnnp-2011-301876.short

      And studies like it, have been done on D3. There might be ones on K2 as well… but I haven’t searched for ’em. As per above, D3 may help slightly, but not much. The primary and most secondary measures showed non-significant differences, and the sample size was somewhat solid at 66 patients.

      I don’t think you’ll be seeing any miracle fixes with vitamins, however applicable.

  18. There’s no doubt that inflammation is a major factor in mental health and disease in general but is it possible that inflammation and oxidative stress can inhibit neurotransmitters like dopamine and serotonin thus affecting mood, behaviour and one’s sense of well being?
    In your podcast on the gut-brain connection you talk about how a large percentage of people with IBS have mental health problems and you did a great job at explaining the cyclical nature of disease and how stress impacts the body as a whole. I can’t disagree with you about inflammation and obviously chronic inflammation and chronic stress are a huge problem but i think there’s a variety of factors that create stress and inflammation. Biological, psychological, social, spiritual factors. I think taking steps to address inflammation like you have explained is a big part of the solution but i believe that unfortunately its more complicated then that and there’s many more factors that may be contributing to the problem and that may need to be addressed. Its a challenging problem to assess and solve or identify and prevent in our modern world and with our modern way of living.

    • Yes, there’s research showing that inflammatory cytokines affect neurotransmitter metabolism. But if that’s the case, the most effective approach will be to reduce cytokine production (i.e. inflammation) rather than focusing on its downstream effects (disrupted neurotransmitter metabolism). This is the primary difference between functional medicine and conventional and even integrative medicine. With a functional approach, we try to identify and then treat the root cause of a problem. With a conventional or integrative approach, it’s often about using drugs or supplements/herbs to suppress/treat symptoms.

      Having said that, depression—like all other modern diseases—is multifactorial and the etiology will differ from person to person. As I mentioned in the article, emotional and psychological factors do play a role and the idea that inflammation is the only cause is overly reductionistic. The point of this article is that inflammation is a major root cause (whether provoked by gut issues, stress, psychosocial problems, sleep deprivation, toxins, etc.) that often goes unexplored.

      • That makes a lot of sense and this is why i’m such a big fan of you and your approach! Your trying to bring attention to a very important and very overlooked factor, which is inflammation what causes it.
        It was your articles on stress and practicing pleasure in your 9 steps to perfect health series and your podcast on the gut-brain axis that really opened my eyes to the bigger picture. You pointed me in the direction of people like Gabor Mate and Robert Sapolski, where i became very aware of the sociological and psychological factors of stress, which i think are often overlooked and unexplored as you say. I’m also intrigued by people like Dr Amen and his use of Brain Spect Imaging.
        I look forward to reading more from you on this subject. People need to become more educated on the complexity of modern health problems like add/adhd, mental health problems, addiction, alzheimers/dementia etc.

        • There is no science or credible research behind Dr. Amens claims about SPECT imaging, but he sure is making a lot of money convincing people that there is. I highly doubt that Chris Kresser would give any credibility to him at all. I’m all on board with this depression – inflamation link though since Chris backs it up with solid science.

          • I hear what your saying about Dr Amen, and i’m not one to judge the science behind Brain Spect Imaging. Inflammation should definitely be the first thing addressed and as Chris explained with the goal of functional medicine, it makes sense to try identify and address the root cause. But i still think Brain Spect Imaging makes a lot more sense then the current typical approach of using pharmaceuticals based on symptoms or to try and to try and correct “chemical imbalances”.

      • Looking for ways to stop inflammation. Tired all the time, have allergies,fibromyalgia,asthma, others.
        Tired all the time.

        • Stop eating wheat and see if you can manage an organic diet. It helped me tremendously with my myositis (muscle inflamation). My whole body was all inflammation, I got completely cured by wheat-free and organic diet, acupuncture/acupressure and some little excercises everyday. This in less than a year. Regular health care told me there was no cure, only painkillers for the rest of my life……..

          • Diet consisting of a lot of organic fruit and veggies builds the immune system – it’s the building blocks of our bodies – do cure a lot of ailments. When a body is cremated, that is the only real substance left of us – the minerals (building blocks). As soon as you fill up your minerals, which is only present in our soil and in organic fruit and veg, the body is able to take up it’s own function of healing itself. You first detect a deficiency and then you do get symptoms and illnesses. By the time there is an illness, the deficiency is big – but can be reversed. Minerals also work on the psycho-somatic level and are able to reverse depression, Alzheimers, ADHD, etc

        • Hi Sue – There are so many great herbs available that can help reduce inflammation – Turmeric is one – you can get it at a bulk section at a health food store/coop. One easy and tasty was to take it is to mix 1 tsp-1 tbs of turmeric powder into a cup of warm milk – also add some ground pepper and maybe tsp or so of coconut oil – these will help you body absorb the turmeric. You can sweeten it with honey and even add cocoa powder if you like which is a great antioxidant. Drink this brew 2x/day.
          Also – wondering if you have been tested for Lyme disease or other tick pathogens as these can cause your symptoms and are so frequently undiagnosed. The best lab for these tests is Igenex – http://www.igenex.com
          Good luck!!

        • You likely have infections. You should consider trying a systemic anti fungal first and antibiotic protocol. I’d try the borax protocol also.

          Your asthma would likely be a fungal infection.

          I have come to the conclusion that there are different types of fibromyalgia. When one reads enough symptom reports, the symptoms seem different.

          Costochondritis is reported by around 70% by people with FMS. This is pretty significant but essentially treated as a separate medical condition. The definition of FMS has been corrupted.

          The medical community is just lumping all the cases in a single category. This makes FMS studies invalid and misleading. I think this is by design. There has never been any real effort to address the disease by the government since they want to keep people sick.

          Even worse, the way they diagnose it is very subjective hence not everyone who has it gets diagnosed.

          I think you have to divide FMS into an infectious and non infectious type. Most people likely have the infectious variety.

          I cured my FMS with an antibiotic called minocin pretty quickly after many decades. Most generic minocyclines will not work although a few specific ones will. They have pushed the price of minocin artificially way up. At least some of the FMS will have mycoplasma infection. You should consider an antibiotic protocol and borax protocol.

          One needs to address any fungal infections first. This could solve the problem by making it more difficult for the mycoplasma infection to thrive.

          Another consideration is that the FMS may be just a secondary infection but still resolvable by addressing the secondary infection.

        • All classic symptoms of hypothyroidism and all your issues are 100% curable with the right natural thyroid treatment. This is a must read book, Hypothyroidism the Unsuspected Illness by: Broda O. Barnes, this book is a major eye opener! Orthodox medicine is not taking the right approach to the majority of our health problems. You can also go to the website “stop the thyroid madness” for other information.

        • Please get checked for Lyme disease by a Lyme literate doctor. I just found out I have it after suffering for months with fatigue, migraine, muscle aches, neck pain…After seeing eight doctors over the course of 7 months it was my naturopathic dr. that ordered the test. I am on antibiotics now and feeling better. I hope you get the answers you need! 🙂

        • Look into Mthfr….20 years fatigue headaches Cf Fibra.M allergies soreness depression anxiety……80 percent gone ….methylation restored with a few supplements methylfolate and methylb12 and go grain/gluten free and eliminate as much folic acid from your diet as u can it’s in everything…good luck

        • Have you been thoroughly tested for Lyme Disease through Igenex? I had/have Fibromyalgia and a laundry list of dx’s from over the years. Found out last year that I actually have Chronic Lyme and several very serious tick borne co-infections. This is a MAJOR issue for so many people and it is being kept quiet by the powers that be.

          Check out the free documentary on YouTube called Under Our Skin. I cannot recommend it highly enough to all people.

          That said, a Paleo diet has helped me more than any other type of treatment. My Fibro pains and symptoms virtually disappear when I eat Paleo/Primally. It’s nothing short of a miracle.

          The chronic fatigue/chronic tiredness is likely reactivated Epstein Barr Virus (EBV). Have you been tested for it? I would be willing to bet that you have it, as most Fibro/CFS patients tend to actually have Lyme Disease which reactivates dormant viruses in the body. This will make you feel like you have Mono 24/7. Just unrelenting tiredness. I know because I have the same thing.

          Plus, with these reactivated viruses and other health concerns, the adrenals get run down. Have you thoroughly tested your cortisol levels? You could be dealing with an adrenal issue.

          Please look into Lyme Disease. Information is conflicting – which is why I urge you to watch the film Under Our Skin so that you can understand why the info is so politicized. https://www.youtube.com/watch?v=CVzXsKvN2ck

          • Also, MTHFR mutations & Mold sickness is extremely common for Lyme patients. I have both issues.

            I struggled with debilitating depression and suicidal thoughts/actions for most of my life up until I finally found out what I’m really dealing with. And with bringing up my B12 levels, eating Paleo, detoxing, changing my hygiene and household products, etc. I have dramatically changed my mental health.

          • EBV has nothing to do with CFS. It is just a secondary infection that only a small number of people with CFS have. Coconut oil works well for EBV.

            Generally Lyme / CFS / Severe MS / FMS / GWS have overlapping symptoms. The powers that be have spent many decades covering up these diseases. Many well known doctors involved with these diseases work covertly for the powers that be along with patient organizations.

            There is no official way to prove what one has because that is the way the powers that be want it. keep things murky. The powers that be already know what causes these diseases but they have made the decision to let people drift in the wind. they do let information out unofficially. Polio disease had the same cover ups.

            They have been coming up with new and improved Lyme tests for decades.

            Separating out MCS from the others is important also.

            I would concentrate on treatments and not focus on what one has. It would be nice to definitively know.

            It’s why I wouldn’t waste my time and risk my health having a colonoscopy etc for anything colon related. It will usually be an infection that needs to be addressed. No matter what tests you have, one is still left with, what does one do for the infection.

            The best way to approach these diseases is the way rheumatoid arthritis is approached.

            This gives a general perspective on how to approach these diseases


            This doesn’t mean everything will get necessarily all cured but if a lot of sickness is removed, it will improve the quality of your life. CFS will have a ciguatoxin involved hence difficult to remove from the body.

            Hayakawa has back tracked from his original ciguatera findings and claimed much of it has mitichondria origins even though he dissected the toxin down to the molecular level in his first studies. His research contracts are with the CDC, NIH, Pentagon etc, the very agencies involved spear heading the cover ups globally. Hence, he needs to talk out of both sides of his mouth. This has resulted in anyone with shellfish poisoning having their tests invalidated also or brought into question.

            You have an infection but can only guess what it is. Now what. The way to circumvent this political game is to take a generic approach to treatment. You might get lucky.

    • Yes, it seems facile and contrived for the author to construct this article as an either / or argument of one causative theory against another. There is evidence of complex malfunction in neurotransmitter systems in many cases of depression. There is evidence of abnormally high levels of inflammatory chemicals and stress hormones as well. It is very liky that neither one of these observations can “explain” depression or even preempt one another in a causative chain. They are merely descriptive findings that can help to guide biological interventions for a complex condition.