Chapter 1
Depression
Depression is a major topic in America today; however, the impact on society is underestimated. The National Institute of Mental Health (NIMH) divides depression into two categories: Major Depressive Disorder (MDD) and Persistent Depressive Disorder (PDD). The NIMH defines Major Depressive Disorder, or Clinical Depression, as causing “severe symptoms that affect how you feel, think, and handle daily activities, such as sleeping, eating, or working. To be diagnosed with depression, the symptoms must be present for at least two weeks.” The Anxiety and Depression Association of America (ADAA), a non-profit organization cultivating further research and education in the field of psychiatry, estimates that in 2016, 16.1 million, or 6.7% of American adults suffered from MDD. As defined by NIMH, Persistent Depressive Disorder, or Dysthymia, causes patients to “have episodes of major depression along with periods of less severe symptoms, but symptoms must last for two years to be considered Persistent Depressive Disorder.” PDD is a subset of MDD. According to the ADAA, of the 16.1 million adults with MDD in 2016, approximately 3.3 million, or 1.5% of American adults, suffer from PDD. Approximately 2-3% of children between the ages of 6-12 are clinically depressed, while 6-8% of teens are clinically depressed. Certain people have a higher risk of developing depression. Some individuals have a genetic predisposition to developing depression, as it is passed down through the generations. Depression is also affected by stressors such as being diagnosed with a chronic illness or making a major medical decision.
Inflammatory Bowel Disease
Inflammatory Bowel Disease (IBD) is a category of autoimmune disease that affects the gastrointestinal tract. IBD consists of Ulcerative Colitis and Crohn’s Disease (see fig. 2). The Mayo Clinic describes the symptoms of Ulcerative Colitis as causing “long-lasting inflammation and sores in your digestive tract. Ulcerative Colitis affects the innermost lining of your large intestine (colon) and rectum.” They describe the symptoms of Crohn’s Disease as causing “inflammation of your digestive tract, which can lead to abdominal pain, severe diarrhea, fatigue, weight loss, and malnutrition. Inflammation caused by Crohn’s Disease can involve different areas of the digestive tract in different people.” The Crohn’s and Colitis Foundation of America, a non-profit organization that is at the forefront of IBD research, estimates that 1.6 million Americans have IBD, of which 80,000 are children. Of the 1.6 million Americans with IBD, approximately 907,000 have Ulcerative Colitis and 780,000 have Crohn’s Disease. Although the exact cause of IBD is unknown, researchers believe that certain factors impact the probability of a person developing IBD. Known risk factors include age, ancestry, smoking, non-steroidal anti-inflammatory drug (NSAIDs) usage, and the environment. IBD often causes severe pain, diarrhea, extreme weight loss, and anemia due to blood loss.
Comorbidity
In comparison to citizens without a diagnosed inflammatory disorder, depression is much more prevalent in citizens with IBD. The American Journal of Gastroenterology (AJG) is a peer reviewed monthly publication from the American College of Gastroenterology (ACG). The ACG is made up of nearly 12,500 physicians from 86 different countries. In an article published by AJG in 2017, researchers from the Mayo Clinic, Washington University in Saint Louis, and University of North Carolina found that out of the 2,798 patients they studied who had Crohn’s Disease, 38% were clinically depressed, and that of the 1,516 patients studied with Ulcerative Colitis, 32% were clinically depressed. In comparison, NIMH estimated that 16.1 million adults, or 6.7% of all American adults, were clinically depressed in 2016. People with IBD are approximately five times more likely to suffer from depression. Alison Feller, of aliontherunblog.com, was diagnosed with Crohn’s Disease at the age of seven. Now 25, Ali explained her feelings during a recent flare:
I just didn’t want to exist anymore. I was in such a state of constant pain and unhappiness from this disease that I didn’t want to be around anymore… Some days I was sad, others I felt angry. Most days, I felt nothing at all. I didn’t respond to emails, I didn’t shower, and I definitely didn’t feel like “fighting”… Everyone kept telling me to “keep fighting!” and it would make me irrationally angry. I wasn’t fighting. I was sitting around, unshowered, covered in fever-induced sweat. I wasn’t trying to leave the apartment. I wasn’t making myself nutritious meals. I was barely surviving. I was letting Crohn’s win, and I had no desire to “fight.”
Depression and IBD are comorbid disorders, which explains why depression is often more prevalent in people with IBD.
Chapter 2
Nervous System
Without the nervous system, there would be no connection between the colon and the brain. The two parts of the nervous system are the central nervous system (CNS) and the peripheral nervous system (PNS), and they communicate through the vagus nerve. The PNS is divided into 4 parts, however the fourth section, the enteric nervous system (ENS) is the most critical for the gut-brain axis:
The enteric nervous system is the one that operates in your gut, your second brain. It is intimately connected with the rest of the nervous system but operates with its own set of rules. This system, including your microbiota, holds the keys to dismantling any chronic stress responses you may be experiencing, and to returning your body to a healthy homeostasis. (Anderson et al., 118)
In the ENS, bacteria produce neurotransmitters such as serotonin, that the nervous system uses to communicate. Serotonin is a neurotransmitter that is responsible for regulating brain activity such as behavior, emotion, body temperature, anxiety, and depression. The gut produces 90-95% of the body’s serotonin supply. When an individual is suffering from IBD or dysbiosis, the resulting inflammatory cytokines cause serotonin production in the gut to decrease. Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) were originally developed to treat MDD; researchers, however, have found that both SSRIs and SNRIs have positive side effects for patients with IBD and other inflammatory disorders:
A 2012 study by Ross Tynan of Australia’s Deakin University established that depression is linked with inflammation and that SSRIs and the related SNRI drugs greatly reduce inflammation of the microglia in the central nervous system. In the journal “Brain, Behavior, and Immunity,” Tynan looked at the ability of five SSRIs ‒ fluoxetine, sertraline, paroxetine, fluvoxamine, and citalopram ‒ as well as one SNRI, venlafaxine, to suppress this inflammation, and he found that they did so powerfully. (as qtd. in Washington 212-213)
These medications reduce symptoms of IBD, and are currently used as anti-inflammatory agents, as well as antidepressants.
When the body is stressed, anxious, or depressed, the gut microbiota become dysbiotic and cr
eate inflammatory cytokines. (see
fig. 3) Through the gut-brain axis, the disrupted microbiota travel back into the brain, causing more depression and anxiety. The actions of the microbiota cause the brain to react negatively:
Take an obvious case like food poisoning. Your microbiota recognize the pathogenic intruders and start to attack them. It tries starving and poisoning them and —importantly— it alerts your immune system. Now kicked into high gear, your second brain prepares to purge your system. It sends you a terse admonition to find a bathroom, quickly. Your mood at that point is acute anxiety. Now imagine that happening day after day. That’s what occurs when you have chronic inflammation, often caused by a breach in your microbiotic defenses. Anxiety and depression can become a constant companion… Nature has wired us to lay low when we have an infection. This is called sickness behavior. (Anderson et al., 17)
Sickness behavior causes individuals to isolate themselves from others. When individuals are chronically ill, they can become isolated for long periods of time. The extended isolation, when combined with inflammation, causes depression, or sickness behavior. Jenni, of jennisguts.blogspot.com, was diagnosed with Crohn’s disease 22 years ago, and has been battling depression ever since. She explains in her post “The Uncomfortable Side of Chronic Illness” how she feels on a daily basis: “I really don’t want to leave my house… I’m scared. I don’t want to come and hang out and pretend to be okay. I’m not okay.”
Vagus Nerve
The entire gut-brain axis relies on stimulation of the vagus nerve. The vagus nerve runs through the spine, connecting the brain to the gut, and sends nerve fibers throughout the entire digestive system (see fig. 4). Most, if not all, communications between the brain and the gut involve the vagus nerve.
Research has shown that just injecting certain cytokines can induce depression. Immune cells produce [inflammatory] cytokines when pathogens show up. The signals quickly reach nerve cells in your gut and are then conveyed to the brain through the vagus nerve, providing information about the type and severity of the inflammation. (Anderson et al., 123)
Along with cytokines, the neurotransmitters produced in the ENS travel through the vagus nerve to reach the brain. IBD and depression, with the help of the gut-brain axis, create a positive feedback loop that is challenging to break.
Chapter 3
Nutrition
Numerous factors affect inflammation, however nutrition is arguably one of the most predominant. American eating habits are regarded as the worst on the planet. American dinner tables are often covered in plates filled with fried foods, refined carbohydrates, and processed meat, as well as glasses filled with sugary soda. These foods all feed the pathogenic bacteria that live in the gut. When the bacteria become accustomed to a certain diet, they become addicted and “[turn] rogue and [dig] into your gut lining, potentially causing bloody diarrhea… this kind of behavior is known as bacterial virulence” (Anderson et al. 57). For individuals with dysbiosis, the likelihood of experiencing bacterial virulence is much higher, as the gut lacks diversity. The lack of microbial diversity in the guts of Americans mimics the lack of diversity in the Western diet.
Research done in 2010 by Dr. Janice K. Kiecolt-Glaser, Ph.D., a professor of psychiatry and psychology at the Ohio State University Neurological Institute, found that the C-Reactive Protein (CRP) levels, an inflammatory marker, in women who ate a Westernized diet was 73% higher than that of the women who ate a Mediterranean diet. Kiecolt-Glaser also found that the level of Interleukin-6 (IL-6), a type of pro-inflammatory cytokine, was 17% higher in the women who ate a Western diet. The U.S. Department of Health and Human Services, the U.S. Department of Agriculture, and the Dietary Guidelines Advisory Committee found that in 2010, only 57.8% of Americans over the age of two followed the recommended dietary guidelines. They recommended that citizens on the generic 2,000 calorie/day diet should consume 2.5 cups of vegetables, 2 cups of fruit, 6 ounces of grains, 3 cups of dairy, 5 ½ ounces of proteins, and 27 grams of oils per day (see fig. 5). This diet, derived from the Mediterranean diet, focuses on balanced nutrients, vegetables, fermented foods, dairy products, seafood, and healthy oils, such as avocado and olive. The Mediterranean diet is an anti-inflammatory diet, and has also been known to reduce symptoms of depression (Berk et al.).
The Mediterranean diet is high in antioxidants, unlike the typical Western diet. Antioxidants help to combat the effects of food additives and oxidative stress. Oxidative stress occurs when cells are deprived of oxygen. This can cause brain cell toxicity as well as have a negative impact on gastrointestinal disorders such as IBD. Many scientists believe that for many individuals, a key factor in the development of depression is brain cell toxicity. The natural environment also impacts brain cell toxicity, depression, and IBD.
Natural Environment
The natural environment has a major effect on depression and IBD (see fig.6). The biodiversity hypothesis proposes that “clinical diseases caused by poor microbiome, immune dysfunction and inflammation, are linked to biodiversity loss” (as qtd. in Tasnim et al.). The amount of environmental biodiversity has been found to affect immune function both positively and negatively. Urban environments are linked to a decrease in microbial diversity, and an increase in inflammation and inflammatory disorders. Inflammatory disorders also have a higher rate of occurrence in urban areas due to the lack of exposure to rural environments that have thousands of bacteria in them. The lack of exposure to bacteria causes the gut microbiome to become nutrient starved, and therefore increases health risks.
Chemicals that are found in the materials used to build urban structures can also negatively impact mental and physical health. People who work in fields that are frequently exposed to pesticides, heavy metals, and other toxic chemicals, are more likely to suffer from depression and other psychiatric disorders. For example, craftsmen who use paints and varnishes, farmers who use pesticides, and those who work at gas stations are at risk for developing depression and other mental disorders, as well as gastrointestinal disorders. This is due to the toxicity of the chemicals they are working with (see fig. 7), and the changes that these chemicals are able to make in their brain. They inhale toxic particulates daily, and the particulates disrupt the brain chemistry.
Conclusion
The two types of depression are Major Depressive Disorder and Persistent Depressive Disorder, and the two types of Inflammatory Bowel Disease are Ulcerative Colitis and Crohn’s Disease. Depression and IBD are comorbid disorders. The gut-brain axis is composed of the brain, the central nervous system, the enteric nervous system in the small intestine and the colon, and the vagus nerve. Neurotransmitters are created in the gut, and travel from the colon to the brain through the gut-brain axis. The Western diet encourages inflammation, while the Mediterranean diet encourages healing. Urban environments are filled with chemicals that are potentially harmful for both the gastrointestinal tract and the nervous system.