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.8,9,10 As I briefly mentioned in Chapter 1, 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.11 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.12 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.13 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.14,15
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.”16 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.17 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.18
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.
Конец
