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The psychological effects of inflammation overload

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The last time Ali Zeck tried to kill herself, she was in a mental hospital. The antidepressants weren’t working, nor were any of the psychiatric drugs she had been taking in various strengths and combinations for nearly 25 years. Diagnosed with an eating disorder in her early 20s, Ali was hospitalized for a few days and sent home with her first prescription, which she was told she’d need for life.

For the next decade, her life was “a daily struggle” with depression and anxiety, swallowing cocktails of pills from an array of doctors, and riding a wild rollercoaster of hypermania and dark depression that was eventually diagnosed as bipolar disorder.

It was a ride Ali barely survived, sometimes crying for hours or days at a time, drinking wine at 10:30 in the morning to “come down” from the hyper-stimulating effect of her drugs and obsessively picking at her skin until she had a serious, marring infection. Her psychotic breaks with reality and suicide attempts had her in and out of psychiatric wards in a downward spiral.

It was in this state, 45 years old and pondering suicide again, that Ali found herself in the Manhattan office of psychiatrist Kelly Brogan, author of A Mind of Your Own and one of a small cadre of doctors who doesn’t view mental illness as a ‘chemical imbalance in the brain’ or a permanent brain disorder, but as a whole-body or systemic disease characterized by a wildfire of inflammation.

The ‘inflammatory model of mental illness,’ as it is sometimes called, has been around for more than two decades, but has become the subject of recent renewed interest. It’s the idea that mental illness, from depression to schizophrenia, is linked to a hyperactive immune system gone awry, leading to psychological symptoms but also to myriad physical problems routinely dismissed as ‘coincidental’ or unrelated.

The inflammatory model of mental illness recognizes that the rash on your face, or your irritable bowel or heart condition, does indeed have something to do with your mood and mental stability. These symptoms are all evidence of an immune system in a chronic state of hyperactivity, either reacting to a stimulus or engaged in an autoimmune attack on the body, or both.

Inflammation is the immune system’s natural response when defending us against invaders such as foreign bacteria and viruses or toxins in pollution or drugs, and the immune system also launches an inflammatory response when we are injured – the redness, swelling and warmth we experience are the result of immune cells rushing in to eradicate threats and assist repair.

However, when our immune system is hyper-stimulated or chronically activated, it can cause trouble. As a very sophisticated defense mechanism, a misfiring immune system can do a lot of damage. Chronic inflammation is a key player behind atherosclerosis1 and the driving force behind autoimmune diseases from type 2 diabetes to multiple sclerosis.2 People with chronic inflammatory diseases such as colitis also have a higher risk of mutations that cause cancer. A 2015 study from the Massachusetts Institute of Technology found that exposure to DNA-damaging chemicals after a bout of inflammation boosts cancer-causing mutations even more.3

The immune system and your brain

While inflammation is a known culprit in other diseases, it has taken doctors longer to consider its role in mental health, but research is beginning to accumulate.

A review published this year confirmed that key immune system regulators – proteins called cytokines that drive inflammation – also impact neurological function and
are altered in patients with depression.4

Earlier studies found that nearly half of patients receiving cytokine treatment for hepatitis also developed depression.5 And those cytokines increase and decrease with the severity of depression.6

Another 2016 review of 114 studies looking at schizophrenia, bipolar disorder and depression found that inflammatory cytokines were similarly disordered in all these conditions.7

And two recent studies have linked childhood obsessive compulsive disorder (OCD) to elevated blood cytokine levels as well.8

Slipping upstairs

In 2017, researchers at Boston Children’s Hospital discovered how inflammation could be impacting brain function when they studied mouse models of lupus, in which the body mistakenly attacks its own organs. This autoimmune condition has symptoms of fatigue, joint and muscle pain and skin rashes – as well as neuropsychiatric symptoms including headaches, depression, anxiety and even seizures in about three-quarters of sufferers.

In lupus, white blood cells release a cytokine called interferon-alpha, which acts like an immune system general, calling other commandoes into play in a sustained assault.

The Boston researchers discovered that interferon-alpha crossed the blood-brain barrier, where it triggered microglia – the immune defense cells of the nervous system – to attack the junctions between nerve cells in the brain.

“We’ve found a mechanism that directly links inflammation to mental illness,” said lead researcher Michael Carroll. “This discovery has huge implications for a range of central nervous system diseases.”9

Just how these immune system combatants get into the brain is still not clear, but in 2015, researchers at the University of Virginia discovered an entire network of previously undiscovered vessels connecting the brain to the immune system, which could be their conduit.10

Why chronic inflammation?

The idea that infection may lead to mental illness has been around for a long time. American psychiatrist Henry Cotton was so convinced of it in the early 20th century that he removed his patients’ infected
teeth hoping to cure them, and if that didn’t work, he tried surgically extracting other potential culprits including tonsils, ovaries and testicles.

That approach eventually fell out of fashion, but it has been well established that certain infections can lead to neurological and inflammatory conditions.

Latent or chronic infection can keep the immune system stoked, and infections such as Epstein-Barr virus and cytomegalovirus have been implicated as hidden causes of inflammatory neurological diseases such as multiple sclerosis.11

A groundbreaking 2017 study by researchers at University College London and Bart’s and the London School of Medicine found that contrary to the belief that once an infection is ‘over,’ the immune system reverts back to its previous state, in fact, healthy volunteers injected with a killed E. coli bacteria had alterations in some immune system markers weeks after their symptoms had passed.12

In other words, having an infection alters your immune system in a lasting way that sets it up for a different inflammatory response to each further infection.

Asked how the experimental infection differed from vaccination, one of the study authors, David Gilroy, says, “they don’t – they’re identical.”

This raises serious questions about our understanding of the effects of repeatedly prodding our immune system with dozens of childhood vaccinations, booster shots and annual flu vaccines.

A 2015 review of the medical literature looked at the evidence linking vaccination with adverse psychiatric symptoms and outlined many mechanisms by which it can augment inflammatory responses linked to mental illness.13

Food fire

Another recent study found that a standard Western diet may provoke the immune system’s inflammatory response just like an infection, making it hyper-responsive to inflammation triggers.

The German research team found that mice fed an unhealthy diet showed an acute inflammation response and activation of inflammatory genes. What’s more, even though the inflammation died down when they were placed back on their normal diet, returning to the healthier diet failed to reverse the changes in their innate immune system, and many of the genes that had been activated stayed active.14

Brain on fire

Repeated infections, injections and long-term assaults to the immune system are like a match to dry grass, but once activated, our immune system doesn’t distinguish between different kinds of stressors to keep the inflammation going. Environmental toxins, certain foods, sleep deprivation or even physical abuse or trauma can keep the immune response smouldering and flaring for weeks, months or years.

Some patients like Ali even describe their worst mental breaks in terms of an inferno. “It would be like my brain was on fire,” she recalls. “I would pass out from sheer exhaustion. I would be up at three, four in the morning, unable to sleep… but then my brain would be on the second my eyes would open.”

Ali and her doctors noted that her symptoms would flare as she approached her menstrual period. “The brain is the ultimate master of hormonal response cycles, and bodily inflammation can influence brain reactivity, leading to further hormonal disarray,” says psychiatrist Brogan, who treated Ali.

Ali also noticed that her mental state would deteriorate after certain foods like pizza, pasta or sugary foods. Sugar can wreak havoc on hormones, causing insulin spikes followed by a crash – and this, in turn, impacts the brain. So Brogan encouraged Ali to follow a strict anti-inflammatory diet, beginning with eliminating all sugar, gluten and dairy, which can provoke inflammatory immune reactions, along with processed foods (which are almost always packed with inflammation-causing rancid or partially hydrogenated oils like sunflower and other vegetable oils, chemicals and hidden sugars).

“I recommend a diet that controls for glycemic fluctuations through elimination of refined carbs and grains, and through high levels of natural fats to push the body to relearn how to use fats for fuel,” says Brogan. “This is the brain’s preferred source.”

Much of the immune system is housed in the gut, especially in the microbes there, which “train” the immune system and help to rebalance it if it is out of whack. Eating probiotic foods such as sauerkraut, which is teeming with healthful bacteria, can restore the gut ecology and help to balance the complicated relationship between the immune system, gut, hormones and brain.

Ali embraced this diet wholeheartedly and made some lifestyle changes recommended by Brogan, including dry skin brushing to encourage lymph drainage and coffee enemas to support her liver. She began daily meditation, listening to a 20-minute guided meditation. Mind-body therapies like yoga, tai chi, qigong or meditation have been shown to enhance genomic expression of anti-inflammatory genes and suppress gene expression linked to inflammation.15

Ali started the practice of kundalini yoga, which she found helpful for alleviating panic attacks. She also used the Emotional Freedom Technique of tapping on acupressure points to help let go of past resentments and curb panic attacks.

The changes were not immediate, but within a few months of following an anti-inflammatory diet and lifestyle, Ali noticed that she was increasingly “level,” “grounded” and “at peace.” She no longer requires medication to sleep and is free of all
psychiatric medications.

Ali was also able to change the fate of her daughter who, at age 20, had recently been prescribed bipolar medication. She taught her the same tools she had used, and her daughter was able to heal without the drugs. “We have the ability not only to heal ourselves but also the next generation,” Ali says. “We have the ability to tell them, ‘Look, there’s a different way you can do this.'”

Inflammation-lowering supplements

Ali’s journey was written up as a case study.16 Her supplements, which included natural glandular extracts, were tailored to her hormone test results, which confirmed a previous diagnosis of polycystic ovarian syndrome (PCOS) and hypothyroidism, plus general mild inflammation. These supplements included:

To support detoxing:


Dosage: 1800 mg, 2 ×/day for 20 days

Sodium alginate

Dosage: 400 mg, 2 × daily

To support the nervous system:

Liver beef natural glandular

Dosage: 500 mg, 2 × daily

Potassium magnesium

Dosage: 70 mg magnesium, 99 mg potassium daily

Adrenal medulla natural glandular

Dosage: 100 mg daily

Omega 3-6-9 oil

Dosage: 1 tablespoon 3 × per week

Hypothalamus natural glandular

Dosage: 500 mg, 2 × daily

Gamma-aminobutyric acid (GABA)

The chief inhibitory neurotransmitter in the central nervous system, GABA reduces neuronal excitability

Dosage: 2 to 4 capsules (100 mg/capsule) as needed for anxiety


An amino acid precursor of L-glutamate and L-glutamine derived from green tea, theanine may have a relaxing effect and promote immune system balancing

Dosage: 200 mg, 2 × daily

To support digestion:

Digestive enzymes

These included betaine, glutamic HCl and pancreatin plus ox bile acid to increase the acidity in the gut, which assists digestion of nutrients

Dosage: 1 capsule with each meal or follow instructions on the bottle

Pancreas natural glandular

Dosage: 3 capsules (1275 mg total) with each meal and 10 capsules (4250 mg) between meals, 3 × daily

To support hormone balance:

Thyroid glandular

Dosage: 1 capsule (40 mg) daily


This is a Peruvian root known for its hormone-balancing properties

Dosage: 2 capsules (1000 mg) before breakfast and lunch


This is a traditional Chinese medicine known for its anti-inflammatory and anti-diabetic effects

Dosage: 1 capsule (200 mg), 2 × daily



Circulation, 2002; 105: 1135-43


Ann N Y Acad Sci, 2018; 1413: 59-68


PLoS Genet, 2015; 11: e1004901


Mol Psychiatry, 2018; 23: 48-58


Psychosomatics. 2003;44:104-112


Psychoneuroendocrinology, 2014; 45: 77-86


Mol Psychiatry, 2016; 21: 1696-1709


Eur Child Adolesc Psychiatry, 2018 Jan 4; J Neuroinflammation, 2017; 14: 261


Nature, 2017; 546: 539-43


Nature, 2015; 523: 337-41


Clin Transl Immunology, 2014; 3: e27


PLoS One, 2017; 12: e0186964


Altern Ther Health Med, 2015; 21(suppl 3): 18-26


Cell, 2018; 172: 162-175.e14


Brain Behav Immun, 2016; 51: 1-11


Adv Mind Body Med, 2017; 31: 4-11

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Article Topics: immune system, inflammation
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