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.1
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.2, 3 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.4
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.5
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.6
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.”7
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
