by Kelly Brogan 

When a woman experiences fatigue, brain clouding, flat mood, PMS, and constipation, we call it anxiety or stress and we stick her on an antidepressant that she will likely take for the rest of her life. Where in this protocol have we investigated why she is feeling that way? How have we personalised the treatment to her unique biochemistry? What is the plan for side effects including new and different psychiatric symptoms resulting from this prescription? We haven’t. We’ve applied a one-size-fits all treatment to mask symptoms without consideration for the cause.

The Immune System and Depression

Psychiatry has known about the role of the immune system in certain presentations of depression for the better part of the last century, and more recently, pioneering thinkers like Maes, Raison, and Miller have written about the role of altered immune set points and inflammation in models of depression. Our immune systems are largely housed in the gut and the interplay between the gut and the brain is a complex and profoundly important relationship to appreciate.

We all recognise that anxiety or nervousness can impact our guts – most of us have had butterflies before a date or even diarrhoea with extreme performance anxiety.

We are just learning that this relationship is bidirectional; however, and that the gut can also communicate its state of calm or alarm to the nervous system.

We think that the vagus nerve is a primary conduit of information and that inflammatory markers are the vehicles travelling this highway. Scientists have studied the “protective effects” of severing this nerve when animals are exposed to gut-related toxins that normally cause depressive symptoms. We are getting ahead of ourselves; however, because we need to better elucidate why inflammation matters, where it comes from, and why it is the universal driver of chronic illness.

How Does Inflammation Start?

When a woman feels foggy, run-down, easily overwhelmed, and flat, we know that her hormones as messengers between her gut and brain are out of balance. From my perspective however, hormone derailment is a downstream effect of cellular dysfunction from oxidative stress and inflammation. Inflammation stems from many sources, including, hallmarks of the modern Western lifestyle:

• Sugar

Sugar, particularly in the form of fructose and sucrose, spikes insulin and triggers the release of inflammatory cytokines. It forms advanced glycation end-products when it binds to proteins, and oxidises lipids which form cell and mitochondrial membranes.

• Chemicals

Pesticides, environmental pollution from industrial waste, hormonally-modulating plastics, fire retardants, and cosmetic additives all stimulate our immune systems to varying extents and disrupt the optimal production of energy on a cellular level, particularly in vulnerable tissues like the thyroid.

• Pathogens

The aforementioned culprits, and notably herbicides, gluten grains, and genetically modified foods, promote intestinal permeability, changes in our intestinal flora that facilitate the growth of pathogenic bacteria, yeast, and fungus which keep our immune systems in a state of alarm.|

• Stress

This catch-all term, broadly defined, represents the ultimate link between hormones and inflammation, because stress, whether it’s psychological or physiological, triggers the release of cortisol. Cortisol helps to mobilise blood sugar so that you can run effectively and efficiently from that tiger chasing you.

Cortisol also acts as a systemic immune suppressant, lowering levels of secretory IgA, an important body guard of the gut mucosa.

Cortisol and insulin are like stress-response sisters. High cortisol states also contribute to insulin resistance, or high insulin and high sugar, while the cells themselves, are starving. Insulin protects fat storage (inhibits lypolisis), and fat cells secrete their own inflammatory signals in addition to aromatising testosterone to oestradiol contributing to states of oestrogen dominance, while also increasing DHEA and androgens to fuel that process (as well as acne, hair growth, and agitation). Cortisol also inhibits the conversion of storage thyroid hormone to active hormone leading to states of hypothyroidism even with normal-looking labs.

What Does Inflammation Do?

Once inflammation is active, it is highly self-perpetuating. These inflammatory cytokines travel throughout the body causing oxidating stress to the fragile machinery of the tissues and mitochondria, specifically. In the brain, inflammation serves to shunt the use of tryptophan toward the production of anxiety-provoking chemicals like quinolinate, instead of toward serotonin and melatonin.This produces a replicable collection of symptoms called ‘sickness syndrome’, noted for it’s overlap with ‘depressive’ symptoms such as lethargy, sleep disturbance, decreased social activity, mobility, reduced libido, learning issues, anorexia, and and hedonia.

Further, psychiatric researchers have observed that patients with higher levels of inflammatory markers (like CRP) are less likely to respond to antidepressants, and more likely to respond to anti-inflammatories.

Where Do We Begin to Heal?

How is any of this good news? This approach to chronic illnesses like depression views it as a complex, non-specific symptom reflecting a state of bodily disharmony. It isn’t that you were born with bad genes or low serotonin.

It is far more likely that you are experiencing an unhealthy inflammatory balance, driven by cortisol dysfunction, and stemming from a sick gut.

We can come at modifying your system from many angles, but here is a basic starter kit:

• Exercise

Burst exercise is my primary recommendation – you get the most bang for your buck in terms of cardiovascular benefit and specifically enhancing mitochondrial health because it puts a special kind of stress on the body when you move to your max for 30 seconds and then recover for 90. I recommend 8 intervals 1-3x/week.

• Meditation

The effects of stimulating the relaxation nervous system, even through listening to a 20 minute guided meditation, can be far-reaching. Enhanced genomic expression of anti-inflammatory genes and suppression of inflammatory ones have been demonstrated in research.

• Diet

I recommend a diet that controls for glycaemic fluctuations through the 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. This is the brain’s preferred source.

Strategic supplementation

Natural anti-inflammatories like polyunsaturated fats (evening primrose oil and fish oil), curcumin (the active component of turmeric), and probiotics to name a few, can help promote a synergy of beneficial effects from the above interventions.

In my practice, despite some suggestion that antidepressants may actually be having their effect through an anti-inflammatory mechanism, these medications have become obsolete. An appreciation of the role of inflammation and immunity in driving hormonal imbalance which directly impacts mood, energy, and wellness, is at the core of personalising the definition of ‘depression’. Don’t be lured into the simplicity of a one disease-one drug model. There’s no room for you in that equation.

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