Depression: more than just the blues

Depression: more than just the blues

The World Health Organization believes that depression may become the biggest health burden in the world within just a few years (by their estimations, 2020).  In the United States, depression affects literally a quarter of the population. But what is depression? Is it really just a serotonin deficiency…or some sort of Prozac deficiency?

The World Health Organization believes that depression may become the biggest health burden in the world within just a few years (by their estimations, 2020).  In the United States, depression […]

Current research has actually been steering us away from the neurotransmitter model of depression for quite some time now, even as the outdated pharmacologic SSRI interventions treating it like a serotonin deficiency continue to persist (what the heck, it still makes drug companies money).

The first thing we need to do is clarify what it is we mean by depression here.  The fact is that at times, feelings of depression (and even anxiety) can be a perfectly normal, adaptive response to certain stressors in your life.  It can make perfect sense to have these emotions under certain circumstances. If someone in your life dies, or if there’s a divorce or some other emotionally devastating calamity then there is almost something a little bit wrong with you if you don’t have any difficult feelings over that. In other words, it’s perfectly normal to feel depressed if your mother or someone else close to you dies. Where this particular emotional state begins to cross the line into its more pathological definition is when a suitable amount of time has passed and you still maintain persistent thoughts and feelings of helplessness and hopelessness that ultimately become a form of imprisonment in your own brain.

In the field of neurofeedback we commonly see a relative lack of left cortical prefrontal lobe activation (sometimes called “cerebral hypoperfusion”)…which is a fancy way of saying that there is circulatory impairment to the part of your brain that regulates this aspect of your mood.

What could possibly cause that?

As I have said many times before in my public lectures and elsewhere, we all see the world through a lens that is our biochemistry—our hormones, our neurotransmitters and (the degree to which we choose to be dependent upon it) our blood sugar.  At any given moment, we all have things we can feel good about and can feel grateful for in our lives.  We also all have things we feel as challenging, troublesome or stressful going on.  What it is we choose to focus on and the attitude we bring to it is largely a result of the quality and clarity of this “lens”.

One way to think about this is that every single physiological process in the human body and every single biochemical reaction in our body and brain are wholly dependent upon the nutrients in our diets and other (perhaps less than nutritive) compromising substances we supply these processes with.  Genes are almost wholly controlled by epigenetic factors (i.e., dietary and other environmental influences).  Therefore, our underlying mental state is very powerfully influenced by what we feed it (on multiple levels). [1] [2]   –Or don’t.

Nutrition absolutely matters here, but depression is also far more than a simple nutritional deficiency. Current research has begun to classify depression within what is called a “cytokine model.” In other words, researchers are increasingly viewing depression as an inflammatory disorder. Although this new understanding goes much farther in addressing the underlying causes of clinical depression, the news here is also not good.  Depression actually underlies every single neurodegenerative process currently known: everything from Alzheimer’s disease and dementia, to Parkinson’s disease and traumatic brain injury.  During a state of clinical depression, in other words, the brain is on fire… And that inflammatory fire has potentially profoundly destructive consequences long-term.  This puts depression more squarely in the realm of immunologic dysregulation than any manner of neurotransmitter deficiency (though it can decidedly powerfully impact the way your body uses those neurotransmitters).

In my book, Rethinking Fatigue: What Your Adrenals are Really Telling You and What You Can Do About It I discussed the mechanisms behind the way certain forms of inflammatory response can have a dampening effect on the part of your brain (the hypothalamus) that releases the neurotransmitters you need in order to feel good. It’s not that your brain can’t make the neurotransmitters, it’s that inflammation is interfering with the way your brain uses them. So adding pharmacologic serotonin-reuptake inhibitors truly isn’t the answer… And the vast majority of the time it isn’t even a temporary palliative.

The actual research used to establish the most commonly prescribed SSRIs as THE gold standard in the treatment of depression pharmacologically actually showed them to be only slightly more effective than a placebo—just about 13% effective.

–-Hardly anything to write home about, much less base the psychiatric treatment of such a serious disorder upon.  Of those actually being helped by SSRIs, at least 40% of the time the positive effect plateaus and eventually back slides.  Interestingly, no antidepressant pill can ever put so much as one molecule of serotonin in your body.  All they do is artificially manipulate biochemical activity at the synapse (the space between your cells where chemical exchanges take place) in order to give your brain the “illusion” of having more serotonin. The problem with this is that over time your receptors in the synapses may start to feel overexposed to the artificial concentration of the serotonin you have there, and they start to down-regulate and become less sensitive to serotonin.  Put another way—it’s like being subjected to a nagging spouse; the receptors just stop hearing serotonin’s message after a while and become deaf to its message.  So when you actually go to try and get off of your antidepressant medication, now not only do you not have any more serotonin than you did before you started taking it, but now you actually have fewer active receptors to attach to the tiny little bit of serotonin you have. Let’s just say that the physiological response to this is often not good. People undergo extremely uncomfortable mental and physical symptoms while trying to get off of SSRIs, and some feel so overwhelmed by the symptoms they don’t feel as though they can stop taking the drug–even as their depression continues to persist.

As if all this isn’t troubling enough, it turns out that at least some of these SSRI medications have even been fraudulently approved!  In September of 2015 the New York Times[3] and UK’s The Guardian[4] exposed Big Parma giant, GlaxoSmithKline (GSK) for doctoring the studies used to promote Paxil as a treatment for depression. Turns out Paxil (notorious for it’s troubling side effects and withdrawal symptoms) was never proven safe or effective in any way—with evidence that they even had opposite effects to those supposedly intended.  For example, according to David Healy, one of the authors of the reanalysis, said that adverse events in the original study involved acts of violence, suicidal thinking and behavior (many instances of which have since occurred) but were mislabeled!  Close to 60 published papers that initially passed the peer-review process have since been pulled from an international journal after the revelation that the supposed reviewers of those studies were secretly bought and paid for.[5]  And this is anything but an isolated incident.  There have been similar frauds, commonly referred to as peer review rings” in the arena of stroke medications[6] and pain management medication[7], as well (just for starters).  This brings many realms of science under suspicion when it comes to not just pharmaceuticals (and other substances manufactured by profit-oriented drug companies for public application), but also almost literally anything potentially designed to profit major industry profits and goals.  Science seems to be increasingly stacking itself in favor of multinational Industry.  It is rapidly becoming extremely difficult to know who and what to trust.  On this subject of “bought and paid for science” and the corruption of truth for-profit, journalist Jonathon Porritt wrote the following in The Guardian back in 2000[8]: “To what extent does the growing commercialisation of science render it unfit (or at least, less fit) to serve the public purpose without fear or favour?”  In reference to GMO–based agriculture and the Biotech Industry (though broadly applicable throughout other forms of industry, as well) he said, “Much of the research is commercially confidential, never sees the light of day, and is carried out with the sole intent of generating future revenue streams.”   In other words, we all basically need to “follow the money.”

So what’s the answer?

Merely addressing the symptoms of depression through pharmacologic palliatives clearly isn’t.  No form of depression (or any other illness, for that matter) can be entirely effectively managed or cured long term without digging deeper to ferret out its physiological root cause. I’m not talking about psychotherapy here– though I would never diminish the value of such a process toward arriving at self-understanding and a healthy recognition of dysfunctional patterns in your life. There is work that can be done in an appropriate and quality psychotherapeutic environment that truly cannot be accomplished any other way. But that’s not what we’re talking about here. We’re talking about the underlying physiological component that is “depression” biochemically impacting the way you see and interpret the world around you through that “lens.”

So what are the possibilities?

A number of issues have become clearly associated with chronic depression:

  • Chronic infections (viral, bacterial, parasitic)
  • Autoimmunity
  • Antigenic responses to certain foods (like gluten) and/or environmental compounds
  • Traumatic brain injury (TBI)
  • Neurodegenerative processes
  • Low thyroid function
  • Dysbiosis and/or SIBO (small intestinal bacterial overgrowth)
  • Chronic clinical/subclinical anemia
  • Other chronic inflammatory conditions

Obviously it pays big to know which one of these situations might be influencing the functioning of your brain.  Treating depression symptomatically is seldom fruitful– and worse yet can result in ignoring something much bigger that might happen to be underlying it.

While you work with your trusted healthcare provider to get to the root of your chronic depressive/inflammatory symptoms, there is quite a bit you can do on your own in the meantime to help support your own healthiest brain state and recovery from depression.

Steps YOU can take today:

First and foremost, getting the sugar (and alcohol) out of your life should be a priority. I am also quite biased toward adopting more of a fat-based, ketogenic metabolism in order to alleviate the dependence upon sugar (glucose) for mood, energy and cognitive functioning. A ketogenic state is automatically anti-inflammatory in effect and can be exceptionally stabilizing to both mood and brain function.  That removes one potentially major issue pretty quickly.  Sugar and the insulin surges commonly associated with it, as well as starch consumption are inherently quite inflammatory. But in addition, sugar and high carbohydrate diets also tend to be very depleting of B-vitamins, magnesium (also needed for healthy mood), as well as tryptophan (required as the most critical amino acid precursor to serotonin); plus sugar also potentially feeds any (inflammatory) pathogens that may be present in your body. There is literally no such thing as a “carbohydrate deficiency” of any kind, so losing the sugar/starch is kind of a no-brainer (no pun intended). It simply helps eliminate one major source of unnecessary complications.

Secondly, just lose the gluten. It literally has no nutritive value and can be profound source of neuro-inflammatory problems. Gluten immune reactivity has been associated with numerous psychiatric disorders[9] [10] [11] and cognitive issues.[12] [13]  –And what do you suppose gluten immune reactivity’s most common neuropsychiatric disturbance is?  –Yep, you guessed it: depression.

In a peer reviewed study in the Journal Alimentary Pharmacology & Therapeutics,[14] the researchers stated, “Depression is reported to be a feature of celiac disease and is ranked as its most common neuropsychiatric disturbance.”  As I also stated in my book, Primal Body, Primal Mind, “Depression has also been found in 67% of patients with untreated celiac disease” (Addolorato et al. 2004).[15]  The same study found that high levels of anxiety are also exceedingly common in such patients (73%). Gluten sensitivity (or the possibility of it) cannot be ignored here as a contributing factor or underlying culprit.  Got depression?  Get rid of gluten.  Yesterday.

Also to be considered are gluten’s potentially cross-reactive compounds– the most common of which involves dairy proteins. Roughly half of everyone having an issue with gluten immune reactivity also has dairy as a cross-reactivity.  Cross-reactivity refers to a form of “molecular mimicry” in which a particularly sensitive immune system may habitually confuse one compound for another. In other words (as an example), that particular sensitive immune system sees gluten and dairy as exactly the same thing (and all this implies).   Also commonly associated with gluten immune cross-reactivity are oats, corn, millet, baker’s yeast and even rice. In addition, some individuals have a particularly pronounced gluten cross-reactivity with something you might not readily expect: processed coffee grounds and instant coffee. –You know, the cheap stuff typically served in low-end cafes and greasy diners?  Avoid it. This caveat does not necessarily include whole, organic roasted coffee beans (which you might want to avoid having too much of for other reasons)– but instead the more highly processed varieties of coffee that either becomes tainted (cross-contaminated) during processing or whose proteins become adversely altered during the processing itself. The precise reason for this is as yet unclear and is still under investigation by immunologic researchers.  I know, weird.

Finally, you don’t have to have an immune reactivity to gluten at all in order for it to damage either your gut or your brain.  Literally ALL gluten consumption leads to a release of the enzyme, zonulin, which controls not only your gut permeability, but also your blood-brain barrier permeability! This can potentially leave you wide open to inflammatory immune reactions to almost anything you eat. Also, a particular lectin associated with the gluten molecule, known as wheat germ agglutinin (WGA) is capable of crossing your blood-brain barrier all on its own, without any associated immune reactivity, attach itself to your myelin (the insulation surrounding your nerve fibers) and block nerve growth factor– effectively leading to a form of brain damage.  Ironically, WGA levels in wheat products are actually highest in those supposedly “healthy sprouted-grain breads.”   Trust me, they’re not so healthy.

The next part of your body you really need to think about supporting during any form of depression is your gut. Your gut and your brain are connected throughout your entire life through a common thread known as the vagus nerve. Through this nerve (unique to us humans) impulses are sent back and forth between the brain and the gut. What happens in one place will invariably impact the other. It literally goes both ways. But any form of gut inflammation is basically guaranteed to have a negative impact on your mood.

Digestive problems are one critical place to look. Poor hydrochloric acid (HCl) production and/or pancreatic insufficiency can additionally impair your body’s ability to properly digest proteins and may create efficiencies of amino acids needed for hormonal/neurotransmitter production.

By the way, if you have GERD (gastro- esophageal reflux syndrome) your problem actually isn’t too much stomach acid (as you may have been told), but invariably not enough.  I talk about this at much greater length in my book, Primal Body, Primal Mind.

Also, low HCl may also significantly impair the proper ionization and utilization of key minerals in your diet, such as zinc, magnesium, iron and others needed for healthy brain and cognitive functioning. Impaired HCl production additionally impairs your gut’s production of intrinsic factor, required for the digestion and absorption of vitamin B12. B12 deficiencies can lead to macrocytic anemia (which would affect anyone’s mood) and if allowed to go on long enough, can result in neurological damage, severe memory dysfunction/dementia and mental instability, irritability, depression and/or paranoia.  Good times.

Also part of the complete digestive equation includes the health of your gallbladder. Biliary issues can greatly impair the digestion and absorption of both fats and critical fat-soluble nutrients–further impairing mineral absorption and proper protein utilization. If you have gallbladder issues it’s going to be important to determine the underlying cause of this in order to effectively address the problem. Common causes of biliary issues include thyroid problems, a history of overly low-fat and/or vegetarian/vegan diets, a diet having too many processed and/or rancid fats, along with possible nutrient deficiencies associated with impaired bile production. If you already have had your gallbladder removed, then 1) you still need to find out what was the issue underlying that in the first place—the underlying problems didn’t all go away simply because your gallbladder did and 2) you will need to effectively compensate for this by finding a source of supplemental bile salts (sometimes sold in health food stores as “ox bile”) in order to provide sufficient support for the digestion of significant fats and fat soluble nutrients. You will need to take these with any fact containing meal basically for the rest of your life if you want to make the healthiest use of fats and fat-soluble nutrients in your diet. Sorry about that.

Cleaning up your diet is definitely an important part of mitigating these issues, but there is another side to this equation:

One of the biggest buzzwords spoken in the hallowed hallways of the natural health genre today is the term, Microbiome.  Let’s face it, 90% of the cells making up the human body aren’t even human– they are actually bacterial! Fully 99% of the genetic material occupying the human organism at-large is fundamentally “alien” (i.e., non-human) in nature. These microscopic hoards occupy every nook and cranny of your “second brain” (i.e., your G.I. tract) in varying concentrations and species as well as elsewhere in the human body (whether they are welcome or not). It stands to reason that these vast populations of living organisms within our own have their own agenda, requirements and varied physiological impact that anyone trying to understand their health or mood has to seriously take into account.  The relative health or pathology of these populations has demonstrably pronounced consequences upon our own.

Gut bacteria (over 1,000 different species numbering up to 100 trillion) are being discovered increasingly to have a major influential role in brain health and functioning, as well as mood.  Gut bacteria both produce and even respond to the same neurochemicals– such as GABA, serotonin, norepinephrine, dopamine, acetylcholine and melatonin that your brain uses to regulate its own moods and cognition. In part, these neurochemicals may align the brain and its behavior to the feedback it receives from the bacteria living in your gut. Obviously, cultivating and maintaining healthy probiotic colonization of your gut should certainly be a priority with any brain-related issue.

Currently, psychiatric disorders thus far connected with the health of the microbiota include:  anxiety, depression, autism/ASD, Alzheimer’s disease, schizophrenia, and eating disorders—to name a few.  The presence or absence of various microorganisms within the gut seems to be able to even powerfully influence the action of key neurotransmitters.  There is also some evidence to suggest that stress and norepinephrine (NE) can also enhance the pathogenicity of certain (gram negative, rod-shaped) bacteria![16]  Less welcome internal riffraff occupying the small intestine in great numbers (known clinically as SIBO, or small intestinal bacterial overgrowth) have been linked to numerous physiological and immunologic consequences, as well as commonly related mood symptoms such as depression.

Although significant dysbiosis and conditions such as SIBO may require a bit more diagnostic work through expanded gastrointestinal panels and clinical workups, including cultured foods in your diet can be one way to add more of the “good guys” to your gut. Cultured vegetables, coconut kefir and yogurt, kvass and some kombuchas have the potential to improve the conditions in your large intestine. If, however gas and bloating persists with the consumption of these foods, along with the consumption of otherwise healthy fibrous vegetables, nuts and seeds… Then it is quite possible that what you have going on is an overgrowth of bacteria in your small intestine. This condition, known as SIBO (small intestinal bacterial overgrowth) typically requires the omission of foods like this until the problem can be properly corrected. Again, seek out a knowledgeable functional medicine healthcare provider having a good understanding of these issues in order to systematically identify and treat the problem.

Dietarily, increasing anti-inflammatory foods/spices into your diet can also be decidedly helpful. Turmeric (and its associated curcumanoids) can be especially useful, as it is one of the few anti-inflammatory compounds that actually is able to cross the blood brain barrier and help with inflammation there. Ginger, too is another potentially useful anti-inflammatory spice.

Avoiding refined table salt can help eliminate another insidious and potent form of inflammation-generator. Full-spectrum see salts like Celtic sea salt and Himalayan sea salt are not similarly inflammatory and should always be used instead.

Deficiencies in essential fatty acids such as Omega-3’s (EPA and DHA fro 100% grass-fed meats/marrow and fatty fish), GLA (gamma linolenic acid) from organ meats, fat-soluble vitamin D3 (from animal fat, full sunlight exposure) and nutrients such as vitamin B6, zinc, iron and magnesium are also potential culprits in the development and perpetuation of depressive problems.

Many people are tempted to call their depressive symptoms a form of “adrenal exhaustion.” I address this concern in expanded detail– offering useful screening tools and helpful suggestions and solutions for addressing various forms of adrenal-related dysregulation in my e-book, Rethinking Fatigue: What Your Adrenals are Really Telling You and What You Can Do About It.  Let’s just say that “adrenal problems” might not be what you or even your natural health care provider thinks. Most of the current approach to identifying and addressing adrenal-related issues are based upon outdated 1950’s science that was actually never proven to be true and has since been dismissed by stress physiology researchers. My book brings this whole subject matter into the 21st century and helps people better identify what is actually happening and (just as importantly) what they can do about it.

Finally, as I wrote about in a soon-to-be published article on the subject of depression for the Townsend Letter and also for a recently published academic book on the subject of Neurofeedback called, ‘Restoring the Brain: Neurofeedback as an Integrative Approach to Health,’ one more condition related to depressive symptoms may need to be ruled out through an inexpensive urinary test: Pyroluria.  As I wrote in the above-mentioned publications,

A little discussed genetic condition known as Pyroluria also seems to affect a significant number of individuals presenting with mental, emotional and cognitive-related issues. It is thought to affect roughly 11% of the population. Individuals identified with Pyroluria produce excess amounts of a bi-product from hemoglobin synthesis called hydroxyhemopyrrolin-2-one (also called OHHPL), which is an otherwise inconsequential waste product. In the case of Pyroluria, excess levels of this metabolite will bind excessively to both zinc and vitamin B6 and can lead to potentially severe deficiencies of these critical nutrients. The condition is diagnosed through the presence of elevated kryptopyrroles in the urine.  This is a subject I cover more extensively in my book, Primal Body, Primal Mind “The condition is very widely recognized within the field of orthomolecular medicine and orthomolecular psychiatry but is little acknowledged within conventional medical circles (mainly due to the fact there are no medications with which to treat it).  The diagnosis and hypothesis of Pyroluria have also been strongly acknowledged and advocated by Carl Pfeiffer, of Emory University, and by staff members at the Princeton Brain-Bio Center, a precursor of the Pfeiffer Treatment Center.”

The condition has profound implications for various aspects of mental and physical health, including neurotransmitter production, immune functioning, cognitive functioning, digestion, and a few hundred or so other things that might happen to be impacted by critical nutrients such as zinc and vitamin B6.  Symptoms can be anywhere from mild to severe and tend to be worsened by increased stress. Nutritional management of Pyroluria generally involves relatively large doses of zinc and vitamin B6 (in the form of P-5-P), as well as added GLA/gamma-linolenic acid supplementation (i.e., black currant seed oil) and diets higher in arachidonic acid and omega-6 fatty acids in general. Omega-3 fatty acids tend to be less well tolerated by this particular population.


I offer an extremely helpful free pre-screening tool/questionnaire based on existing symptoms associated with Pyroluria in my book, Primal Body, Primal Mind, as well as on my personal web site, www.primalbody-primalmind.com.

In conclusion, as I have frequently stated elsewhere, from a foundational macronutrient perspective there is literally nothing at all more stabilizing to the human brain than healthy, natural dietary fat and nothing more commonly destabilizing the dietary sugar and starch.  Immune reactivity to various foods and environmental compounds ranks a very close second in impact upon your overall health and mood.  Supporting your digestive health and microflora are clearly also critical.

In conclusion:

Obviously, depression can be a complicated condition to fully unravel, and frequently is interwoven with complicating issues such as traumatic emotional history, stress, gut-related issues and chronic inflammatory response. It pays to be a good detective and get to the bottom in order to more permanently address the problem. One thing is for sure–depression is not and never was a Prozac deficiency and it also doesn’t just fall out of the sky. By maintaining the healthiest possible nutritional foundations and cultivating a healthier, nutrient-dense, Paleo-oriented, fat-based diet and ketogenic metabolism you are laying the foundation for health and healing that simply cannot be accomplished any other way!

[1] Egger, G., Liang, G., Aparicio, A., and Jones, PA. “Epigenetics in human disease and prospects for epigenetic therapy.” Nature 429, 457-463 (27 May 2004) | doi:10.1038/nature02625

[2] Aaron D. Goldberg, C. David Allisemail, Emily Bernstein.“Epigenetics: A Landscape Takes Shape.” Cell, Volume 128, Issue 4, p635–638, 23 February 2007. DOI: http://dx.doi.org/10.1016/j.cell.2007.02.006

[3] Benedict Carey. “Antidepressant Paxil Is Unsafe for Teenagers, New Analysis Says”. New York Times, September 16, 2015.

[4] Sarah Boseley. “Seroxat study under-reported harmful effects on young people, say scientists.” The Guardian. Wednesday 16 September 2015.

[5] Henry Fountain. “Science Journal Pulls 60 Papers in Peer-Review Fraud.” The New York Times. July 10, 2014

[6] Lenzer J. Why we can’t trust clinical guidelines. BMJ 2013;346:f3830

[7] Sarah Rubenstein. “A New Low in Drug Research: 21 Fabricated Studies.” Wall Street Journal Health Blog.  March 11, 2009

[8] Jonathan Porritt. “Bought and paid for.” The Guardian. Wednesday 31 May 2000

[9] Margutti P, Delunardo F, Ortona E. Autoantibodies associated with psychiatric disorders. Curr Neurovasc Res. 2006 May;3(2):149-57. Review

[10] Matsunagab, H., Kimuraa, M., Tatsumia, K. , et al.  Autoantibodies against four kinds of neurotransmitter receptors in psychiatric disorders  Journal of Neuroimmunology Volume 141, Issues 1–2, August 2003, Pages 155–164

[11] Michael E. Benros, MD; Berit L. Waltoft, MSc; Merete Nordentoft, DrMedSc; et al.  Autoimmune Diseases and Severe Infections as Risk Factors for Mood Disorders: A Nationwide Study.  JAMA Psychiatry. 2013;70(8):812-820. doi:10.1001/jamapsychiatry.2013.1111

[12] Hu WT, Murray JA, Greenaway MC, Parisi JE, Josephs KA. Cognitive impairment and celiac disease. Arch Neurol. 2006 Oct;63(10):1440-6

[13] Bushara KO. Neurologic presentation of celiac disease. Gastroenterology. 2005 Apr;128(4 Suppl 1):S92-7. Review

[14] Hallert, C., et al. July 2002. “Evidence of Poor Vitamin Status in Coeliac Patients on a Gluten Fee Diet for Ten Years.” Alimentary Pharmacology & Therapeutics 16, no. 7:1333-39

[15] Addolorato, G.,et al. 2004. “Regional Cerebral Hypoperfusion in Patients with Celiac Disease.” The American Journal of Medicine 116, no. 5:312-17

[16] Lyte M, Ernst S. Catecholamine induced growth of gram-negative bacteria. Life Sci 199250203–212.212

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