A Mind of Your Own: The Truth About Depression and How Women Can Heal Their Bodies to Reclaim Their Lives

To me, the worst part of the misguided mess we’ve made of mental health care is that we are missing out on the potential for true resilience and self-healing. Safe, effective alternatives to help us through these passages in life do indeed exist. Perhaps most concerning to a holistic physician is data that suggests that long-term antidepressant treatment actually compromises the benefits of exercise!

The effects of exercise have been shown to be comparable to Zoloft but can be diminished when combined with Zoloft; patients relapse at higher rates than they do with exercise alone. I’ll be going into much greater detail about exercise in Chapter 7 (#litres_trial_promo), and I’ll share why I think this is the case. Exercise is an antidote to depression best used without antidepressants.

Mental health will always be grounded in whole body health. When you discover the real imbalances underlying all your symptoms—­physical and mental—­and take steps to address them, you can restore your health without resorting to problematic drug treatments and endless psychotherapy.

The next question to answer is: What kind of “imbalances” come under the veil of depression? We’ll find out in the next chapter.

CHAPTER 3 (#ulink_6e5deae3-4aa4-5c1c-b923-5eb3818ba69b)

The New Biology of Depression (#ulink_6e5deae3-4aa4-5c1c-b923-5eb3818ba69b)

What Gut Microbes and Silent Inflammation Have to Do with Mental Health

Depression is often an inflammation-driven condition, not a neurochemical deficiency disease.

_____

The most powerful path to our brain—­and peace of mind—­is through our gut.

Pick up any health or diet book published recently and you’ll likely read about the ills of chronic inflammation and the blessings of the human microbiome. The two have been the science buzzwords of late, and for good reason. These concepts reflect the zeitgeist of the modern patient because we have reached a point in our collective evolution where our health is being outpaced by lifestyles that are not aligned with how we are biologically designed to live. We are idle when our bodies want to move, we eat foods that are unrecognizable to our systems, and we expose ourselves to environmental factors that assault our cells. This incompatibility is creating serious internal conflict and driving rampant levels of chronic inflammation like an alarm that won’t shut off.

Inflammation is often described as underlying virtually every chronic condition and illness, from obesity, heart disease, and diabetes to degenerative illnesses including dementia and cancer. I’ve already mentioned inflammation dozens of times already, because science is telling us that depression is also an inflammatory condition. In this model, depression is a general fever that tells us little about what is actually causing the body to react and protect itself in this way. The body is “hot,” and we need to understand why. Depressive symptoms are merely the manifestation of many downstream effects on hormones and neurotransmitters, but if we were to swim up to the source, we would find a river of inflammatory markers coursing by. The source itself may be a single culprit, such as a dietary ingredient to which the body adversely reacts or a collection of culprits that have indirect effects on the internal workings of the brain because of their impact on the immune system and stress response. In fact, the relationship between depression and inflammation is so compelling that researchers are now exploring the use of immune-altering medications to treat depression.

Researchers are desperately searching for the next frontier because the current model is in crisis. As you have seen, modern psychiatry has served as a repository for the diagnostic and therapeutic limitations of conventional medicine. When a patient’s symptoms of malaise, “brain fog,” lethargy, inattention, insomnia, agitation, and flat mood slip through the cracks of the discrete territories of specialty medicine, the patient is referred for psychiatric treatment. When she is treated with nonsteroidal anti-inflammatory drugs (NSAIDs), statins, acid blockers, antibiotics, and birth control pills, the effects of these medications are poorly grasped by prescribers, complaints are dismissed, and she is again referred for psychiatric care. What happens when psychiatric care itself is predicated on medication treatment, with placebo-driven short-term effects and worse functional outcomes in the long term? Perhaps it is time to acknowledge the failures of this paradigm.

Now that the scientific literature has demolished the serotonin model of depression, it can no longer stand on its own, and throwing more and more medications at a perceived false target is doing more harm than good. It’s fitting that psychiatry would follow the investigative path of other chronic diseases such as arthritis, asthma, certain cancers, diabetes, autoimmunity, Alzheimer’s disease, and heart disease—­all of which can be the result of lifestyle barbs that drive inflammation.

Today the concept of psychoneuroimmunology has supplanted the myopic serotonin premise in the primary literature.

This new model reveals the interconnectedness of multiple systems—­the gut, brain, and immune systems—­and takes us out of a one-gene, one-ill, one-pill narrow perspective. The field of psychiatry has known about the role of the immune system in the onset of depression for nearly one hundred years. But only recently, thanks to better technology and large, long-term studies that reveal the impact of the relationship between immunity, inflammation, gut flora, and mental health, have we really begun to understand the relevant connections.

Given our new awareness of the complexity of these connections, including the role of the microbiome, biology as we know it must come under revision, especially when applied to its direct human application in medical interventions. No longer can we say “she was born with it”—­the dismissive meme that dominated a large part of twentieth-century medicine. Nor can we say that the same exposure causes the same illness in all ­people. According to conventional medicine, different genetic problems or infectious exposures cause different diseases for which there are distinct, one-pill solutions. And out of that “broken and vulnerable body” theory came the “me versus the microbial world” mentality. René Dubos, the famous microbiologist and early pioneer in the developmental origins of health and disease as well as the one to develop the first clinically tested antibiotic, warned us of the dangers of classical germ theory half a century ago:

[M]an himself has emerged from a line descent that began with microbial life, a line common to all plant and animal species . . . [he] is dependent not only on other human beings and on the physical world but also on other creatures—­animals, plants, microbes—­that have evolved together with him. Man will ultimately destroy himself if he thoughtlessly eliminates the organisms that constitute essential links in the complex and delicate web of life of which he is a part.

Awareness of the role of microbes in our day-to-day life has brought us to a radical new understanding of the indelible fusions between the functions of the gut and brain. In fact, the role of the brain-based immune system has only been elucidated in the past ten years, and while many questions remain, the facts are swiftly building up to make an incontrovertible case against pharmaceuticals and for wholly natural approaches to wellness. In the words of Drs. Paula Garay and A. Kimberly McAllister of UC Davis, who address so-called immune molecules (the cells and their substances that respond to internal and external threats):

. . . the sheer number of immune molecules that could be important for nervous system development and function is staggering. Although much progress has been made in the past 10 years in our appreciation that immune molecules play critical roles in the healthy brain, the large majority of immune molecules have not yet been studied for their presence and function in the brain. For the immune molecules that we know are important, almost nothing is understood about their mechanisms of action.

Why hasn’t this message made it to those who still believe we can safely manipulate human behavior through psychotropic drugs or that we shouldn’t be concerned about the effects of immune-disrupting substances in our environment, from ingredients in foods to vaccines? Drug products were developed without even basic knowledge of this relevant physiology, let alone the implications for the role of the immune system in neurology. Only recently have scientists begun to look at how certain antipsychotics, including antidepressants, change the native tribes of bacteria in the body and render patients vulnerable to other health conditions. The drug desipramine, for example, has been shown to alter the composition of microbes in the mouth, causing dry mouth and gingivitis. Another example: olanzapine changes the microbial balance with results including metabolic injury and weight gain—­especially in women. Remember, not until 2015 did we even know that the brain has a lymphatic system with a primary purpose of connecting it to the immune system. As the authors of that 2015 Nature paper stated: “The discovery of the central nervous system lymphatic system may call for a reassessment of basic assumptions in neuroimmunology and sheds new light on the aetiology of neuroinflammatory and neurodegenerative diseases associated with immune system dysfunction.”

It’s time for that reassessment. It’s time for disciplines like psychoneuroimmunology to take shape and provide a more accurate context for our understanding—­those that honor the known and unknown complexities of the human organism in its environment.

So with all that in mind, let’s deconstruct what is known about depression as it relates to inflammation and the gut-brain dance. I’ll start with some basics about inflammation.

THE INFLAMMATORY MODEL OF DEPRESSION

As we all know, the immune system is essential to human health and well-being. It helps coordinate the body’s response to its environment, from chemicals and medications to physical injuries and infections, essentially maintaining the critical divide between what is “self” and what is “other.” At the heart of a healthy immune system is an ability to experience appropriate forms of inflammation, which I’ll assume you’re familiar with from a rudimentary level—­the inflammation, for example, that accompanies a paper cut or sprained ankle. These reflect inflammatory responses we can actually feel and sometimes see (such as redness, swelling, and bruising). In this instance, inflammation is part of a necessary biological cascade enabling the body to defend itself against something it believes to be potentially harmful, and subsequently recalibrate. When the trigger for inflammation becomes chronic, the effects can be directly toxic to our cells. Unlike the inflammation that follows bruising your arm or skinning your knee, this more silent, ongoing inflammation deep inside has a meaningful connection to your mental health.

The brain lacks pain receptors, so when we’re showing signs of depression we can’t feel inflammation in the brain like we do in a laceration or arthritic hip. Nonetheless, scientific research has clearly demonstrated over and over again that inflammation underlies the development of depression (and most other chronic diseases).

Several messengers relay information about inflammation between the brain and the body. A variety of inflammatory markers—­chemical messengers called cytokines that tell us inflammation is occurring—­are elevated in those with depression. These include markers like C-reactive protein and cytokines such as interleukins one and six (IL-1 and IL-6) and tumor necrosis factor alpha (TNF-α). Elevated cytokines in the blood have not only been shown to relate directly to a diagnosis of depression, but they are predictive of depression. In other words, the inflammation may be the trigger of rather than the response to depression.

As I briefly mentioned in Chapter 1 (#ub28fb01d-f61f-54db-8eaf-582e3408146e), one of the most predictable side effects of interferon therapy for hepatitis C is depression. In fact, 45 percent of patients develop depression with interferon treatment, which appears to be related to elevated levels of inflammatory cytokines IL-6 and TNF.

But there’s also compelling literature suggesting that even stress, specifically psychosocial stress, can cause this inflammation by mobilizing immature immune cells called macrophages from your bone marrow to start the inflammatory process.

So you can see how inflammation lies at the heart of a vicious cycle; the process can trigger depression just as it can be aggravated by depression.

Researchers have further found that in melancholic depression, bipolar disorder, and postpartum depression, white blood cells called monocytes turn on pro-inflammatory genes that lead to the release of cytokines, while leading to decreased cortisol sensitivity.

Cortisol, you’ll recall, is the body’s chief stress hormone; it’s also a buffer against inflammation. When your cells lose their sensitivity to cortisol, they become resistant to cortisol’s message, and the result is prolonged inflammatory states. It helps to keep in mind that broadly speaking, the stress response largely dictates the inflammatory response and its perpetuation.

Once triggered in the body, the inflammatory agents transfer information to the central nervous system, typically through stimulation of major nerves such as the vagus, which connects the gut and brain (more on this shortly). Specialized cells in the brain called microglia represent the brain’s immune hubs and are activated in inflammatory states. In activated microglia, an enzyme called IDO (indoleamine 2, 3-dioxygenase) stimulates the production of biomolecules that can result in symptoms such as anxiety and agitation. These are just some of the changes that may conspire to let your brain in on what your body may know is wrong.

Researchers have also observed that ­people with higher levels of these inflammatory markers are more likely to respond to anti-inflammatories than to antidepressants; this helps explain why curcumin (the golden-colored antioxidant in turmeric), a powerful anti-inflammatory made by nature, has been found to be superior to Prozac and especially effective when medication isn’t.

One of the most important takeaways from the new information gained about the role of inflammation in depression, in particular a continuous state of low-grade inflammation and the stress signals associated with it, is that in many cases it tends to be generated from an unlikely source: the gut. In millions of ­people today, the gut is largely disrupted due to something called intestinal dysbiosis. Let me explain.

LEAKY GUTS FANNING THE FLAMES OF INFLAMMATION AND DEPRESSION

First, some basic anatomy. Your gastrointestinal tract, the tube that goes from your esophagus to your anus, is lined with a single layer of epithelial cells. It’s the largest mucosal surface, and this intestinal lining has three main functions. It’s the means through which you obtain nutrients from the foods you eat. It prevents potentially harmful particles, chemicals, and organisms from getting into your bloodstream. And it’s the home to specialized cells that patrol and present to the immune system suspected invaders. The immune system provides chemicals called immunoglobulins that bind to foreign proteins to protect the body from them.

The body uses two pathways to absorb nutrients from the gut. One moves nutrients through the epithelial cells (transcellular); the other moves nutrients between the epithelial cells (paracellular). The connections between cells are called tight junctions, and as you can imagine, each of these complex, exceedingly small intersections is regulated. If they somehow become compromised and overly permeable, a condition called “leaky gut” develops. And because these junctions act as gatekeepers—­keeping potential threats that will provoke the immune system out—­they greatly influence levels of inflammation. We in the medical community now know that when your intestinal barrier is damaged, a spectrum of health challenges can result, not the least of which is depression.

What happens is that when these tight junctions are compromised, undigested food particles, cell debris, and bacteria components can sneak by to stir trouble in the bloodstream with downstream effects that manifest in depressive symptoms. To quote one team of researchers from Belgium: “There is now evidence that major depression (MDD) is accompanied by an activation of the inflammatory response system and that pro-inflammatory cytokines and lipopolysaccharide (LPS) may induce depressive symptoms.”

Later on, we’ll see how ingredients like gluten, sugar and artificial sweeteners, casein proteins (dairy), and processed vegetable oils can activate the immune system and result in pro-inflammatory cytokines coursing through your system. But let’s look at what LPS alone could be doing. This is an interesting area of study just coming into view.

THE LPS BOMB

Lipopolysaccharide (LPS) is not only a mouthful of a word, but it’s among the most villainous of biological threats. It flips on inflammatory pathways in the body like a switch. LPS is a combination of lipids (fat) and sugars, and is found on the outer membrane of certain bacteria that are naturally found in the gut, representing as much as 50 to 70 percent of the intestinal flora. LPS serves to protect these bacteria so they are not digested by bile salts from the gallbladder. LPS is not supposed to travel beyond the interior of the gut, however, but it can if the gut lining is somehow compromised.

LPS induces a violent inflammatory response in humans—­so violent that it’s also termed endotoxin, meaning a toxin that comes from within.

It’s used experimentally in laboratory research to instantly create inflammation in animal models to study the full array of illnesses rooted in inflammation, from inflammatory bowel disorders, diabetes, lupus, rheumatoid arthritis, and multiple sclerosis to depression, Parkinson’s disease, Alzheimer’s disease, and even autism. In a healthy individual whose intestinal lining is intact, LPS cannot gain entrance into the bloodstream by those tight junctions. But when the cells lining the intestines (remember: the intestinal wall is only one cell thick) are damaged or become impaired and those junctions are compromised, LPS is able to pass into the systemic circulation, where it sets off an alarm and triggers inflammation. Levels of LPS in the blood are in fact indicative of both leaky gut and inflammation in general.

Researchers around the world are finally looking at LPS as playing a pivotal role in depression. After all, inflammatory markers correlate with depression, and LPS increases the production of these inflammatory chemicals. And here’s where the science really shouts out to me: LPS not only compromises the gut by making it more permeable, it can also trespass the blood-brain barrier, bringing the pro-inflammatory message there as well.

In 2008, the same Belgian researchers I quoted above documented a significant increase in the level of antibodies in the blood against LPS in individuals with major depression. Interestingly, the authors commented how major depression is often accompanied by gastrointestinal symptoms. And it’s one of the most logical explanations given the latest science is the fallout from a disrupted gut community. This is why we must focus on gut permeability and the tribes within the gut that are supposed to be protecting that intestinal lining.