Microbes And Brain Health

CHAPTER 1:

INFECTIONS AND TOXINS AS A CAUSE

OF BRAIN AUTOIMMUNITY

THE MENTAL HEALTH CRISIS

: A MISUNDERSTOOD EPIDEMIC

Did you know that toxins like Lyme, bartonella, mold, and viral infections can contribute to depression, anxiety, poor memory, mood swings, poor attention, and other mental health issues?

Microbes can seriously affect and even damage mental health. Increasingly, research is showing that microbes such as the Borrelia bacterium that causes Lyme Disease, mold toxins, or a virus like Epstein-Barr can all be major root causes of mental illness.

In this e-book, we will review some specific microbes which affect mental health:

● You will see how symptoms of infection can overlap with mental disorders

● You will learn precisely how research has shown that these microbes affect mental health and brain function

● We will overview some of the most important lab tests for toxins and infections

● Finally, we will end with the broad treatment strategies used in our Functional Medicine clinic that can help you address these microbes and get your mental health back on track

Before we connect how microbes can cause mental health concerns, the question arises: how important is mental health and how big of a problem are mental illnesses?

It may or may not surprise you that conservative estimates from the National Institutes of Health (NIH) state that at least 1 in 5 US adults experience mental illness and 1 in 20 experience serious mental illness.

Although the statistics on US adults are somewhat grim, the research on adolescents in the US is even worse. The National Comorbidity Adolescent Supplement (NCS-A,

1 Mental Illness, N. A. on. (2022, June). Mental health by the numbers NAMI. Retrieved February 5, 2023, from https://www.nami.org/mhstats

2010)2 estimated that 49.5% of adolescents had at least one mental disorder and 22.2% of those were severely impaired as a result. The figure below outlines the data.

With nearly half of adolescents experiencing mental illness, this issue has reached epidemic proportions. Because this data is pre-pandemic there have been data since that suggest a much greater prevalence today. If a less strict criteria were to include mental health problems that are not quite to the level of diagnosable mental illness, easily a majority of the US population would be included as struggling with their mental health. Clearly the current treatments and solutions are not adequate for the level of the problem. Luckily, there is research supporting testing and treatments that

2 Merikangas KR, He JP, Burstein M, et al. Lifetime prevalence of mental disorders in U.S. adolescents: results from the National Comorbidity Survey Replication--Adolescent Supplement (NCS-A). J Am Acad Child Adolesc Psychiatry. 2010;49(10):980-989. doi:10.1016/j.jaac.2010.05.017

are not being routinely utilized in the field of mental health. This e-book will serve to reveal some of the researched causes that are often missed and what kinds of solutions are available to reduce or eliminate the reasons for mental health symptoms to arise in the first place.

SEROTONIN AND DEPRESSION: AN ANTIQUATED PARADIGM

Observational studies linking diets low in the amino acid tryptophan with depression date back to the 1960s. The theorized hypothesis at the time was suggesting that the depletion of tryptophan was leaving the body devoid of enough of the amino acid precursor for the neurochemical serotonin. Because tryptophan gets converted into serotonin, the correlative link to depression from tryptophan-depleted diets was enough to generate a strong momentum towards proposing a serotonin-centric explanation for symptoms of depression. By the 1990s, pharmaceutical companies had developed a drug class called Selective Serotonin Reuptake Inhibitors (SSRI). These drugs were developed as “antidepressants” and touted the serotonin theory of depression as proven and unquestioned.

Despite the popularity of the serotonin theory of depression and the strong reliance on SSRI medications as one of the foremost pharmaceutical treatments for depression, until 2022 there was no comprehensive literature review critically synthesizing and analyzing the data to see if the evidence supports the theory. One such review was published in July of 2022 and has shaken the very foundation upon which modern medicine has viewed the causes of and treatments for depression.

When “The serotonin theory of depression: a systematic umbrella review of the evidence” was published (Moncrieff et. al., 2022)3 many experts expected a conclusive synthesis supporting the statistically significant link between serotonin and

depression. However, the article concluded that there is “no consistent evidence of there being an association between serotonin and depression” and further that there is “no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations” (Moncrieff et. al., 2022).3

Worse still, long-term use of SSRI medications may lower serotonin concentration. Despite this evidence, many medical and mental health professionals perpetuate the notions that depression is primarily connected with neurochemical imbalances.

So, if not serotonin depletion, what does cause depression? How does this change the paradigm around main root causes for how and why mental illnesses develop? What does research support as a stronger hypothesis for causes of why mental health dysfunction forms? If research does support causes for mental illness, what testing can help identify those causes? And if able to identify researched root causes, are there good treatments?

These are the questions that this e-book seeks to answer. In particular, the focus of this e-book is around research, testing, and treatment for chronic infections and toxins as causes of mental illness.

3 Moncrieff J, Cooper RE, Stockmann T, Amendola S, Hengartner MP, Horowitz MA. The serotonin theory of depression: a systematic umbrella review of the evidence [published online ahead of print, 2022 Jul 20]. Mol Psychiatry. 2022;10.1038/s41380-022-01661-0. doi:10.1038/s41380-022-01661-0

WHICH MICROBES CAN CONTRIBUTE TO MENTAL ILLNESS?

Post-infectious onset of mental illness has been observed for many decades. Around 1998, observations of children developing mental health disorders in the weeks or months after strep infection led researchers to begin to investigate a possible connection. Case studies of dramatic and sudden onset of OCD and tic disorders in children were presented by Susan Swedo et al at the US Institute of Mental Health.

Case studies inspired research which suggested there is indeed a link between some infections (not just strep) and antibodies against brain tissue. While somewhat overly simplistic, a basic way to understand how this occurs is that when the immune system is combating some infections, the protein structure of the infectious organism may look a lot like some brain tissue. For example, dopamine receptor antibodies are one that has been shown to elevate in some people post infection and reduce after treatment for infections. The immune system is trying to combat infection and inadvertently starts to attack brain structures in the process. If the infection becomes chronic or the autoimmune process continues, changes to brain chemistry and neuroinflammation that result from the brain autoimmunity can cause the onset of mental health disorders.

At first the diagnosis was described as “Pediatric Autoimmune Neurophsychiatric Disorders Associated with Streptococcal infections” (PANDAS). However, other types of infections such as borrelia burgdorferi (the bacteria that causes Lyme disease), Epstein-Barr Virus (the virus that causes mono), bartonella (the bacteria that causes cat-scratch fever), and more were shown to also be linked with increased brain structure antibodies. Thus, the diagnostic label was expanded to be called “Pediatric Acute-onset Neuropsychiatric Syndrome” (PANS) to include other infections. More

recently, clinicians and researchers have suggested removing “pediatric” because it has become clear that adults can also contract infections that can initiate a brain autoimmunity process leading to mental health dysfunction and children are not the only ones affected.

While many types of infections have been linked to brain autoimmunity and many more are theorized to also potentially be connected, there are several that Dr Miles and the Medicine with Heart clinic find to be prevalent as causes of mental health disorders. In fact, it was by accident that Dr Miles discovered the connection. He became sought out by people struggling with mold illness, Lyme disease, bartonella, Epstein-Barr Virus, and other chronic infections. Most people were coming in complaining of chronic fatigue, pain, digestive problems, hormone imbalance, and significant challenges feeling good about their life and prospects for what the future might hold. When evaluating their case history, many reported depression, anxiety, OCD, extreme food sensitivities, eating disorders, brain fog, difficulties concentrating, memory issues, and other mental health struggles. Because most people relegate mental health to the domain of psychologists and psychiatrists, most people did not come into the clinic seeking resolution of mental illness and did not add these issues as main complaints or focus for the treatments.

To Dr Miles surprise, treating infections or toxins from mold led to many people reporting significant improvements in mental health. Severe anxiety, debilitating depression, intense brain fog, food sensitivities, and more were getting better and sometimes reversing completely. This inspired Dr Miles to devote much of his free time to researching, investigating, and working in the clinic with the view that potentially infections and toxins may be significant players in the mental health picture.

Out of the clinical experience of Dr Miles and the Medicine with Heart clinic, 5 main categories of infectious / toxin causes of mental illness have stood out as significant.

STREP:

Group A beta-hemolytic streptococcal (GABS) infections were the first to be linked in children with obsessive-compulsive disorder (OCD) and tic disorders. Later, additional behavioral and mood problems like eating disorders, anxiety, depression, insomnia, motor or sensory issues, and increasing food sensitivities.

The onset of these neuropsychiatric symptoms comes after strep throat, but there may be weeks or even months delay due to the time required for antibodies against brain tissue to cause structural damage and neuroinflammation enough to cause symptoms.

Whether symptoms and autoantibodies resolve with treatment of the strep bacteria and to what degree the strep bacteria can become chronic and systemic are currently being investigated and researched.

LYME DISEASE:

Lyme Disease is a bacterial infection, caused by the bacterium Borrelia burgdorferi. Borrelia is most commonly spread by a bite from an infected black-legged tick.

Lyme Disease is a complex inflammatory disease with both acute and potentially chronic symptoms. It typically, but not always, starts with:

● Rash: Erythema Migrans or “bullseye” rash between 3-30 days after infection (may not look like a bullseye and sometimes but not always there is rash at the site of the tick bite and other times rashes arise in different areas later)

● Headache

● Fever and chills

● Muscle and joint aches

● Swollen lymph nodes

Lyme disease can possibly develop into more serious symptoms such as arthritis, neurologic, or cardiac issues. In the worse-case scenarios, it can seriously affect a person’s quality of life.

Common long-term Lyme Disease symptoms include:

● Pain of any type including joint pain, neck stiffness, muscle pain, or nerve pain (often receives a diagnosis of arthritis, fibromyalgia, and/or neuropathy)

● Chronic fatigue ranging from mild low energy to complete exhaustion

● Hormonal imbalance including thyroid, reproductive hormones, and adrenal hormones (often low blood pressure, low blood sugar, frequent urination go together with chronically low levels of ACTH which stimulate adrenal hormones like cortisol, DHEA, and antidiuretic hormone)

● Cognitive problems ranging from brain fog to cognitive decline

● Neurological issues such as headaches, motor or sensory control issues, and in severe cases symptoms such as seizures (people can experience strange

electrical sensations, feelings like some is crawling inside their body or brain, severe temperature dysregulation, and other hard to describe symptoms)

● Neuropsychiatric problems such as depression, anxiety, panic, obsessive-compulsive disorder (OCD), eating disorders, significant irritability sometimes bordering on rage, low tolerance for stress (getting frustrated about or reacting to things that previously would not have been a big issue)

● Facial palsy (droop or loss of tone on one or both sides of face)

● Inflammation in the brain and spinal cord (can manifest with a variety of mood, cognitive, and pain symptoms)

● Dysautonomia: problems with the autonomic nervous system which can manifest with a variety of symptoms such as some of the following

○ Postural orthostatic tachycardia syndrome (POTS): causes elevated heart rate often when transitioning from sitting or laying down to standing. This can go together with shortness of breath and in some people chest pain or fainting.

○ Problems with balance, sensitivity to noise and light, blurred vision, sleeping problems, chronic headaches, erectile dysfunction, difficulty swallowing, general weakness, and more

● Cardiac / heart issues such as Lyme Carditis (inflammation in the heart muscle itself), heart arrythmias (irregular heart beat), heart palpitations, tightness in the chest, dizziness, and tachycardia (fast heart beat).

Additionally, Lyme Disease is the great mimicker; it can look like literally dozens of other illnesses. Lyme Disease is not completely understood in the medical world.

LYME CO-INFECTIONS:

A Lyme Disease co-infection occurs when someone is infected with Lyme and other diseases transmitted by the same tick. A tick can carry disease-causing microbes or co-infections in addition to Borrelia. Once bitten, it is possible to contract Lyme and one or even more co-infections simultaneously.

The possible Lyme co-infections include:

● Bartonella

● Anaplasmosis

● Babesiosis

● Powassan virus

● Borrelia miyamotoi (relapsing fever-like illness)

● Ehrlichia muris (which causes ehrlichiosis) (Eisen, 2018).

Co-infections can also be stand-alone. You could be infected with Babesia or Bartonella, for example, without getting Lyme. People may get a co-infection with two pathogens, or even three, although it is rare to have a three-pathogen infection (Kumar M, 2019).4 People who live in endemic tick areas, such as the Northeast US are at a higher risk (Kumar M, 2019).4

4 Kumar M, Sharma A, Grover P Triple Tick Attack. Cureus 2019;11(2):e4064. Published 2019 Feb 13. doi:10.7759/cureus.4064

The frequency of co-infections depends on what diseases the specific tick is carrying. But co-infections are common, especially in people with chronic Lyme. This is likely why people with chronic Lyme have such a compromised quality of life.

MOLD TOXINS:

Mold toxins (mycotoxins) are biotoxins that can cause illness after mold exposure:

● Mold often grows in moist and water-damaged buildings. Exposure to mold can lead to the accumulation of mycotoxins in your body.

● The United States Environmental Protection Agency (EPA) estimates that between 1 in 4 and 1 in 2 American homes foster damp conditions that are ripe for mold growth. This may be a conservative estimate.

● Approx. 1 in 4 people have a genetic abnormality which prevents mold and other toxins from being detoxified and properly removed from the body.

● For these people, even having a single exposure can cause mold toxins to circulate in the body and causing many symptoms including fatigue, pain, migraines or headaches and others.

Mold is a significant and under-examined issue that contributes to chronic inflammation and illness. It is compounded by the fact that approximately 50% of buildings are water damaged and have not been remediated properly.

VIRAL INFECTIONS:

A virus can be a significant cause of illness, inflammation, immune problems and mental health issues. Viruses like Epstein-Barr, herpes simplex virus, chicken pox / shingles, and now COVID-19 are common and evidence suggests that some can become

latent and chronic and potentially reactivate. Everyone contracts viral infections and most people most of the time are able to recover and continue with their life. However, many are not aware of a connection with mental health concerns and do not consider that onset in the weeks or months after a viral infection may be connected.

Bacterial infections which often are fully eliminated from the body and completely resolve (some we mentioned early are exceptions to this such as Lyme and bartonella). Viral infections, on the other hand, often remain in the body at low levels even after the acute symptoms resolve. Once you get over a viral infection such as Epstein-Barr Virus, it tends to remain dormant in the body. A virus can be re-activated at any time. Stress is one of the main triggers for reactivation. When the immune system becomes overwhelmed by something else a virus can become active again. If you are under constant stress and too weak to fight the virus off, it can develop into a chronic underlying viral infection. Other bacterial or parasitic infections and exposure to toxins like mold toxins or toxic metals can also trigger the reactivation of latent viral infections. Even other viruses such as COVID-19 may be able to reactivate other dormant viruses like Epstein-Barr Virus.

Chronic viral infections can cause:

● Unexplained symptoms and flare-ups

● Inflammation and connected symptoms such as pain

● Fatigue and/or insomnia

● Development of autoantibodies that can lead to autoimmunity

● Neuroinflammation or brain antibodies that can lead to mental health issues

CHAPTER 2:

CONNECTING MENTAL HEALTH AND

CHRONIC INFECTIONS

MENTAL HEALTH DISORDERS AND MENTAL ILLNESS

In chapter one we reviewed the alarming statistics on the epidemic of mental illness in America today. We discussed the antiquated paradigm around mental health disorders such as depression being primarily caused by neurochemical imbalances such as serotonin deficiency causing depression. The data do not support that connection and we reviewed some of the more contemporary theories for causes of mental health issues related to infections and toxins.

This chapter will explore in more depth mental health concerns and infections and where they may overlap or have causal links. There will also be discussion of the interplay between chronic infection symptoms and chronic illness in general taking a toll on mental health regardless of whether brain autoimmunity or neuroinflammation are causing or worsening mental illness.

MICROBES AND MENTAL HEALTH

Chronic infections, autoimmunity, chronic inflammation, and psychosocial stress can affect mental health. They can trigger psychiatric conditions such as schizophrenia, autism spectrum disorder, bipolar disorder and depression (Pape K, 2019).5

Chronic infections can worsen the severity of Lyme disease or mold illness. The reverse is also possible; Lyme or mold illness can worsen imbalances that are already present in the body. What came first can be difficult to identify. Either way, Lyme, mold and chronic infections may induce brain autoimmunity and/or cause or worsen

5 Pape K, Tamouza R, Leboyer M, Zipp F Immunoneuropsychiatry - novel perspectives on brain disorders. Nat Rev Neurol. 2019;15(6):317-328. doi:10.1038/s41582-019-0174-4

neuroinflammation. Additionally, some infections can secrete or produce toxins and the cell walls of gram-negative bacteria contain lipopolysaccharide (LPS) which is considered an endotoxin and has been shown in research to elevate pro-inflammatory cytokines. These toxins play a significant part in the inflammatory process and can contribute to many different mild or serious health issues. Some additional ways in which microbes can connect with mental health:

● Microbes or pathogens that affect the brain may result in psychiatric symptoms (Benros ME, 2013)6

● Different types of viruses, including Epstein-Barr Virus (EBV), herpes, and chickenpox / shingles have been associated with mental illnesses (Canli, 2014)7

● One study found that any history of hospitalization for infection is associated with a 62% increased risk of later developing a mood disorder, such as depression and bipolar disorder (Benros ME, 2013)6 Autoimmunity, a condition where the immune system attacks itself, can be triggered by infection and may contribute to mental disorders. A history of an autoimmune disorder increases the risk of a future mood disorder by 45% (Benros ME, 2013).6

Unfortunately, these types of infections from bacteria (such as Lyme & co-infections), viruses (such as EBV, herpes simplex, COVID-19 & others) or biotoxins (mold) can be overlooked by your doctor. If this happens, symptoms will persist because you don’t

6 Benros ME, Eaton WW, Mortensen PB. The epidemiologic evidence linking autoimmune diseases and psychosis. Biol Psychiatry. 2014;75(4):300-306. doi:10.1016/j.biopsych.2013.09.023

7 Canli T Reconceptualizing major depressive disorder as an infectious disease. Biol Mood Anxiety Disord 2014;4:10. Published 2014 Oct 21. doi:10.1186/2045-5380-4-10

get the right treatment. The infection can quickly become a chronic problem that can deteriorate overall health.

Chronic underlying infection is one of the first potential root causes we look at in our Functional Medicine clinic, alongside gut dysregulation, hormonal imbalance, nutrient deficiencies, detoxification issues and others.

WHAT IS A MENTAL HEALTH DISORDER?

Mental health disorders are a wide range of behavioral or psychological conditions that affect mood, thinking, state of mind and behavior. They can affect all aspects of life and create distress for the person suffering from symptoms. Examples of mental illness include depression, anxiety disorders, schizophrenia, eating disorders and addictive behaviors.

Disorders are typically going to be mental health concerns that are significant enough to impair ability to function fully and significantly reduce quality of life. Many more subtle and minor mood imbalances would not get a diagnosis as a mental health disorder. A much more significant percentage of the total population experiences periodic symptoms of depression and anxiety without having a mental health disorder.

Little-known facts about mental health disorders:

● 1 in every 8 people in the world live with a mental disorder (GBD, 2022)8

8 Institute of Health Metrics and Evaluation. Global Health Data Exchange (GHDx), (https://vizhub.healthdata.org/gbd-results/, accessed 5 Feb 2023).

● 1 in 5 people in the United States struggle with a mental illness (NIMH, 2022)9

● Mental disorders involve significant disturbances in thinking, emotional regulation, or behavior

● 1 in 100 deaths worldwide are from suicide (WHO, 2021)10

● Anxiety and depression are the most well-known mental health conditions

9 Substance Abuse and Mental Health Services Administration. (2021). Key substance use and mental health indicators in the United States: Results from the 2020 National Survey on Drug Use and Health (HHS Publication No. PEP21-07-01-003, NSDUH Series H-56). Rockville, MD: Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration. Retrieved from https://www.samhsa.gov/data/report/2020-nsduh-annual-national-report.

10 Suicide worldwide in 2019: global health estimates. Geneva: World Health Organization; 2021. Licence: CC BY-NC-SA 3.0 IGO.

WHAT IS MENTAL ILLNESS?

Many people may temporarily have a mental health issue at some point in their lives. A mental health concern becomes a mental illness when symptoms are ongoing, cause frequent stress and affect the person’s ability to function. A mental illness can cause problems in daily life, at work or in relationships.

Mental health conditions fall into several major categories. The different types of mental illnesses include:

● Mood disorders such as depression or bipolar disorder

● Anxiety and panic disorders

● Personality disorders such as antisocial or narcissistic personality disorders

● Psychotic disorders such as schizophrenia

● Eating disorders such as anorexia or bulimia

● Trauma-related disorders such as PTSD

● Substance abuse disorders such as alcoholism

DIFFERENTIATING MENTAL ILLNESS AND CHRONIC INFECTION

While the two are often connected and sometimes even causally linked, it can be helpful to overview some of the most common symptoms that are associated with each. This can help in some cases to identify when there are symptoms of both present. If you or someone you know are experiencing symptoms of both mental illness and also some of the symptoms of chronic infections, the case for investigating the potential for a causative link between the two becomes more convincing.

COMMON SYMPTOMS OF MENTAL ILLNESS

Symptoms can vary tremendously depending on the disorder, circumstances, and other factors. Mental illness symptoms affect emotions, thoughts, and behaviors.

Signs and symptoms of mental illness can include:

● Feeling sad or down

● Confused thinking or reduced ability to concentrate

● Excessive fears or worries or extreme feelings of guilt

● Extreme mood changes with highs and lows

● Withdrawal from friends and activities

● Significant fatigue, low energy or problems sleeping

● Detachment from reality or delusions, paranoia, or hallucinations

● Inability to cope with daily problems or stress

● Difficulty understanding and relating to situations and to people

● Problems with alcohol or other substance abuse

● Major changes in eating habits

● Sex drive changes

● Excessive anger, hostility, or violence

● Suicidal thinking

● Unexplained and/or specific aches and pains

COMMON SYMPTOMS OF CHRONIC INFECTION

In medical research, we see that the symptomatic presentation of certain infections and mental health conditions is similar. (Canli, 2014).7 Lyme, co-infections, mold, and viruses can exhibit symptoms that are similar to those of mental illness.

The following are symptoms of chronic infection that have a significant overlap with symptoms of mental illness:

● Difficulty concentrating, confusion or cognitive issues including brain fog

● Inability to function, not being able to handle stress

● Insomnia

● Various types of pain

● Fatigue

● Loss of appetite and weight loss

● Hallucinations or suicidal thoughts

● Severe headaches

● Irregular heartbeat

● Dizziness or shortness of breath

Many of these mental health symptoms can co-arise with mold exposure, Lyme disease, other toxins and/ or infections. In turn, mental health challenges can cause or worsen imbalances in the body’s hormonal, nervous, gastrointestinal, detoxification and methylation systems. In order to heal from mental illness and chronic disease, it helps to identify and address these imbalanced root causes.

THE LINKS BETWEEN CHRONIC INFECTIONS AND MENTAL ILLNESS

In chapter 1 we covered some of the most prominent mechanistic links between infections and mental illness. The post-infectious brain autoimmune process was described as one of the main ways in which autoantibodies against brain structure and brain inflammation (neuroinflammation) can be caused. Some additional insights into how infections may lead to mental health issues are overviewed in this section.

HOW CAN CHRONIC INFECTION (LYME, MOLD, VIRUS) TRIGGER FOR MENTAL ILLNESS?

In this section, we highlight some of the physiological mechanisms of action (MOAs) or the ‘How’ of infection and mental illness. Understanding the mechanisms can help us to identify root causes.

MOAs common to mental health disorders include (Pape K, 2019)11:

● Pro-inflammatory cytokines (immune system cells)

● Molecular mimicry (which happens in autoimmunity)

● Autoantibodies (also involved in autoimmunity)

● Self-reactive T cells (immune system cells)

● Disturbance to the blood-brain barrier (which protects the brain from toxins)

● Microglial cell: immune cells that make up 10% of cells in the brain (Augusto-Oliveira M, 2019)12 activation (which causes inflammation in the brain)

11 Pape K, Tamouza R, Leboyer M, Zipp F. Immunoneuropsychiatry - novel perspectives on brain disorders. Nat Rev Neurol. 2019;15(6):317-328. doi:10.1038/s41582-019-0174-4

12 Augusto-Oliveira M, Arrifano GP, Lopes-Araújo A, et al. What Do Microglia Really Do in Healthy Adult Brain?. Cells. 2019;8(10):1293. Published 2019 Oct 22. doi:10.3390/cells8101293

NEUROINFLAMMATION

Inflammation in the brain negatively affects brain health and is connected to virtually all types of mental illness. Mood disorders such as depression, anxiety, autism, dementia and schizophrenia have all been linked to inflammation in the brain. These mental illnesses, and others, including ADD, ALS, Multiple Sclerosis, Alzheimer’s and Parkinson’s disease are all inflammatory diseases of the brain.

As we reviewed earlier how depression is not connected to serotonin depletion. What then does more contemporary research suggest is connected? Aside from infection as a cause, there is a significant body of research that outlines what is called the “cytokine theory of depression”. This hypothesis postulates that inflammatory proteins called cytokines in the bloodstream can cross the blood-brain barrier and cause neuroinflammation. This neuroinflammation and resultant activation of the microglia can cause depressive symptoms. Of course, this then begs the question of what the source(s) of the inflammatory cytokines might be. We have already reviewed infections and toxins as sources of inflammation. What else can cause systemic inflammation?

Other sources of inflammatory cytokines aside from infections and toxins:

● Some foods and nutrient imbalances may increase inflammation. An example would be excessive omega-6 polyunsaturated fatty acids from industrial seed oils like corn oil, soy oil, peanut oil, sunflower oil, safflower oil, etc have been identified to be pro-inflammatory. This is especially in the presence of omega-3 (such as EPA and DHA from fish) insufficiency.

● Gut dysbiosis has been linked in research with depression and inflammation. The vagal nerve connection between the brain and gut is one mechanism and

another is that intestinal permeability (aka “leaky gut”) can lead to gram-negative bacteria getting into the blood stream and causing inflammation systemically.

CHAPTER 3:

BRAIN INFLAMMATION AND

AUTOIMMUNITY

WHAT CAUSES BRAIN INFLAMMATION?

Infections like Lyme, mold and viruses are a key root cause of inflammation in the brain (and entire body).

Encephalitis, or inflammation of the brain is commonly caused by a viral infection like herpes simplex virus (Ellul M, 2018).13

Some Lyme patients still suffer from neurological issues even after treatment. Brain scans can show persistent neuroinflammation after a full course of antibiotics. This is because remnants of Borrelia, the bacteria that causes Lyme, can spread into the brain tissue (Parthasarathy G, 2022).14 Antibiotics may kill the bacteria, but remnants can remain and cause ongoing inflammation. In fact, these remnants are even more inflammatory than live, intact bacteria. Further, there is evidence that perhaps what have been thought of as remnants may actually be what are referred to as persister cells which have been shown in petri dish studies to actually regrow into fully formed bacteria after antibiotics were applied.

This explains some of the neurological symptoms and conditions that may persist after a Lyme infection (Parthasarathy G, 2022).14

13 Ellul M, Solomon T. Acute encephalitis - diagnosis and management. Clin Med (Lond). 2018;18(2):155-159. doi:10.7861/clinmedicine.18-2-155

14 Parthasarathy G, Gadila SKG. Neuropathogenicity of non-viable Borrelia burgdorferi ex vivo. Sci Rep 2022;12(1):688. Published 2022 Jan 13. doi:10.1038/s41598-021-03837-0

Exposure to molds, mycotoxins and water-damaged buildings can also cause neuropsychiatric symptoms and inflammation. People who are unable to properly detoxify mold may have symptoms of pain, fatigue, increased anxiety, depression and cognitive issues when exposed to a moldy environment.

Symptoms from mold exposure are extremely similar to those caused by immune system activation after a bacterial or viral infection (Harding CF, 2020).15

Mold illness causes brain inflammation in the hippocampus, the part of the brain involved in memory, learning and the sleep-wake cycle (Harding CF, 2020).15 Patients with mold illness experience a decrease in the formation of new brain cells, anxiety and other neurological symptoms (Harding CF, 2020).15

15 Harding CF, Pytte CL, Page KG, et al. Mold inhalation causes innate immune activation, neural, cognitive and emotional dysfunction. Brain Behav Immun. 2020;87:218-228. doi:10.1016/j.bbi.2019.11.006

AUTOIMMUNITY

In addition to the specific autoantibody attack against brain structures, there is some evidence that any autoimmune process may contribute to neuroinflammation. In this section we go over autoimmunity in more detail to better understand the links.

AUTOIMMUNITY BASICS

Autoimmunity occurs when the immune system mistakenly attacks itself. The immune system has a very sophisticated way to attack foreign and toxic substances to kill them off and protect the body. Sometimes, the system that is meant to protect us gets confused and attacks its own tissue. This is what happens in autoimmunity.

In a basic, healthy immune response, the immune system produces antibodies to protect against an unwanted foreign or toxic substance that can get into the body. A great example is mold toxins. Antibodies, made by the immune system, bind to these foreign substances (i.e., mold toxins) and eliminate them from the body.

AUTOANTIBODIES EMERGE WHEN THERE IS AUTOIMMUNITY

Autoantibodies are:

● Mistakenly made by the immune system

● Pathogenic dangerous antibodies that attack cells of your own body

Instead of reacting to the foreign substance entering the body, autoantibodies respond to cells in the body that look like the foreign substance. In some cases, autoantibodies

can cause an abnormal immune response. This over-reactive response is called an autoimmune response and can lead to the development of autoimmune diseases. With bacterial and viral infections, antibodies are produced to destroy the pathogenic bacteria or virus. If the immune system is over-activated, an antibody reaction can be too vigorous and become autoimmune. In this case, the immune system mistakenly attacks healthy cells. This kind of attack can happen in any part of the body, including the brain. If the immune system mistakenly attacks healthy brain cells, there is autoimmunity and inflammation in the brain. Over time, this can lead to neuropsychiatric symptoms.

Representation of autoantibodies attacking a brain neuron

AUTOANTIBODIES IN THE BRAIN

Autoantibodies (the self-attacking antibodies caused by autoimmunity) attack parts of the brain. New research is identifying specific circumstances in which autoantibody attacks occur in the brain. For example, anti-NMDA receptor encephalitis occurs when the immune system creates autoantibodies that target NMDA receptors in the brain (Gibson LL, 2020).16 NMDA receptors play an important role in learning and memory, and are critical for spatial memory (Gibson LL, 2020).16 With a persistent autoantibody attack on NDMA receptors, the function of the associated cognitive areas can begin to deteriorate.

AUTOANTIBODIES AGAINST DOPAMINE

In another type of brain inflammation or encephalitis, called basal ganglia encephalitis, autoantibodies target the basal ganglia part of the brain (Chain JL, 2020)17 and receptors which may include the dopamine receptors.

When autoantibodies bind to or block dopamine receptors, the brain malfunctions causing neuropsychiatric symptoms. The autoantibodies also cause inflammation in the basal ganglia. This can contribute to symptoms like obsessions, compulsions, tics, ADHD-like behavior, mood swings, seizures, anxiety and depression (Chain JL, 2020).17 The cause of these brain issues is infection, inflammation and autoimmunity. They are

16 Gibson LL, McKeever A, Coutinho E, Finke C, Pollak TA. Cognitive impact of neuronal antibodies: encephalitis and beyond. Transl Psychiatry. 2020;10(1):304. Published 2020 Sep 1. doi:10.1038/s41398-020-00989-x

17 Chain JL, Alvarez K, Mascaro-Blanco A, et al. Autoantibody Biomarkers for Basal Ganglia Encephalitis in Sydenham Chorea and Pediatric Autoimmune Neuropsychiatric Disorder Associated With Streptococcal Infections. Front Psychiatry. 2020;11:564. Published 2020 Jun 24. doi:10.3389/fpsyt.2020.00564

all inter-linked and can negatively affect brain functioning contribute to mental disorders. In addition to dopamine antibodies, infection-induced antibodies against tubulin and lysoganglioside (immune system attacking neurons) amongst other structures have also been linked. The entire extent of the functional implications of these antibodies remains to be seen. There may be problems with learning, memory, attention, and many other aspects of brain function that result from the insult to the brain tissue through this autoimmune process.

AUTOIMMUNITY, THE BLOOD BRAIN BARRIER, AND MENTAL ILLNESS

Recent research shows that patients with psychiatric disorders have an increased incidence of both bacterial and viral infections (Belz, 2018).18 In one study, the risk of developing a mental illness increases depending upon the number and severity of infections the individual has had over their lifetime (Köhler-Forsberg O, 2019).19 There seems to be an ‘infection load’ that influences brain health and mental disorders. The blood brain barrier protects the brain and prevents toxins in the blood from entering the brain. Stress, infection, and inflammation can compromise the integrity of the blood brain barrier. (Zong S, 2017)20 When the blood brain barrier becomes ‘leaky,’ autoantibodies enter the brain and may attack brain tissue. This can then result in dysfunctional behavior, affecting emotions and cognition (Zong S, 2017).20 If autoantibodies get into the brain through a leaky blood brain barrier, they can cause

● Inflammation in the brain, aka “neuroinflammation”

● Overactive immune cells

● Possibly damaged brain tissue

18 Belz M, Rehling N, Schmidt U, Wiltfang J, Kis B, Wolff-Menzler C. Bacterial infections among patients with psychiatric disorders: Relation with hospital stay, age, and psychiatric diagnoses. PLoS One 2018;13(12):e0208458. Published 2018 Dec 4. doi:10.1371/journal.pone.0208458

19 Köhler-Forsberg O, N Lydholm C, Hjorthøj C, Nordentoft M, Mors O, Benros ME. Efficacy of anti-inflammatory treatment on major depressive disorder or depressive symptoms: meta-analysis of clinical trials. Acta Psychiatr Scand. 2019;139(5):404-419. doi:10.1111/acps.13016

20 Zong S, Hoffmann C, Mané-Damas M, Molenaar P, Losen M, Martinez-Martinez P Neuronal Surface Autoantibodies in Neuropsychiatric Disorders: Are There Implications for Depression?. Front Immunol 2017;8:752. Published 2017 Jul 5. doi:10.3389/fimmu.2017.00752

Autoimmune causes of brain inflammation have been reported to be at least as common as viral causes in one study (Uy CE, 2021).21 As autoimmunity continues to affect more and more of the population, it is expected that the growing range of autoimmune causes of brain inflammation will become more common than infectious causes of brain inflammation (Uy CE, 2021).21

21 Uy CE, Binks S, Irani SR. Autoimmune encephalitis: clinical spectrum and management. Pract Neurol 2021;21(5):412-423. doi:10.1136/practneurol-2020-002567

RESEARCH LINKING AUTOIMMUNITY AND MENTAL ILLNESS

The link between behavior and immune function has been hypothesized for many decades. In particular, autoimmune encephalitis demonstrates how abnormal autoimmune targeting of certain proteins in the brain can result in neuropsychiatric symptoms (Sæther LS, 2022).22 The high incidence of autoimmune disorders with neuropsychiatric features shows the likely cross-reactivity of autoantibodies with brain antigens (Kayser MS, 2011).23 The following examples support the effects of autoimmunity on mental health.

Autoantibodies have been seen in schizophrenia patients as early as the 1930’s. There are antibodies to various neurotransmitter receptors, like dopamine, in the brains of psychiatric patients.

Viruses cause classical inflammation and low-level neuroinflammation. Recent research supports that viral infections, virus-related products, or virus-induced autoimmunity plays a role in the development mental illnesses (Bechter, 2013).24

Mold patients report cognitive, physical, and emotional symptoms. Neuropsychological testing indicates damage from mold exposure is similar to that from mild TBI.

22 Sæther LS, Ueland T, Haatveit B, et al. Inflammation and cognition in severe mental illness: patterns of covariation and subgroups [published online ahead of print, 2022 Dec 28]. Mol Psychiatry. 2022;10.1038/s41380-022-01924-w. doi:10.1038/s41380-022-01924-w

23 Kayser MS, Dalmau J. The emerging link between autoimmune disorders and neuropsychiatric disease. J Neuropsychiatry Clin Neurosci. 2011;23(1):90-97. doi:10.1176/jnp.23.1.jnp90

24 Bechter K. Virus infection as a cause of inflammation in psychiatric disorders. Mod Trends Pharmacopsychiatry 2013;28:49-60. doi:10.1159/000343967

Mycotoxins may do damage through inflammatory responses mediated by cytokines (Ratnaseelan AM, 2018).25

25 Ratnaseelan AM, Tsilioni I, Theoharides TC. Effects of Mycotoxins on Neuropsychiatric Symptoms and Immune Processes. Clin Ther. 2018;40(6):903-917. doi:10.1016/j.clinthera.2018.05.004

CHAPTER 4:

HOW TOXINS AFFECT MENTAL

HEALTH AND COGNITIVE FUNCTION

MOLD, MAST CELLS, AND MENTAL ILLNESS

As overviewed earlier in this book, mold is a prominent issue much more prevalent than most people realize. With between one fourth and on half of American homes with damp conditions and with one in four Americans genetically predisposed to have trouble identifying and eliminating mold toxins from the body, the recipe is there for significant issues to arise for many.

Because of the genetic relationship between mold toxin accumulation being a much bigger deal for only about a fourth of the population, many people discount the home as a source of their symptoms and chronic illness because a spouse or family member or housemate does not seem to have the same symptoms or does not seem ill. This can lead to the environment being unsuspected and missed in diagnostic evaluations.

However, there is a clear link between exposure to mycotoxins in those genetically predisposed to not get rid those toxins efficiently. The bioaccumulation of this toxin in tissue and potentially organs including the brain, can lead to chronic and systemic inflammation. In fact, the diagnosis given to those dealing with biotoxin accumulation from mold is called Chronic Inflammatory Response Syndrome (CIRS). Multiple markers of inflammation tend to remain elevated sometimes even long after being exposed to mold toxins.

HOW MOLD EXPOSURE CAN CONTRIBUTE TO NEUROPSYCHIATRIC DISORDERS

Research has shown that insusceptible individuals, mold exposure has the potential to mitochondrial function and could lead to apoptosis (cell death) in neurons. In mice,

mold can produce apoptosis in sensory neurons and inflammation via pro-inflammatory cytokine immune cells in the brain (Ratnaseelan AM, 2018).25

Mycotoxins, from mold exposure, can stimulate mast cells and microglia. Many pro-inflammatory cytokines are secreted from mast cells, which are found in all tissues including the brain. Mast cells and microglia (immune cells in the brain) interactions are linked to neuropsychiatric disorders, and especially ‘brain fog’.

As mentioned previously, mast cell proliferation and increased inflammation can cause a ‘leaky’ blood brain barrier. This happens via an increase in mast cells and cytokines, allowing circulating environmental toxins to get into the brain, trigger microglia proliferation and inflammation and disrupt neuronal connectivity or the transfer of information between brain cells (Ratnaseelan AM, 2018).25

Recent research is showing an association between environmental triggers, mast cell proliferation, and an increased risk for autism.

Here are some recent possible connections:

● People with autism show signs of localized inflammation in the brain

● Autism is 10 times higher in children with mastocytosis (a condition caused by an excess number of mast cells) than in the general population (Ratnaseelan AM, 2018)25

CHAPTER 5:

LAB TESTING AND ASSESSMENT FOR

INFECTIONS AND TOXINS

TESTING FOR MICROBES AND TOXINS

While laboratory testing is not perfect when it comes to infections and toxins, there are some good tests to identify possible root causes for mental health. Testing can be done for antibodies against infections and also against brain tissues and structures. Inflammatory markers associated with mold toxin bioaccumulation and urinary mycotoxin testing is also available. The genetic predisposition to accumulate toxin from mold more than the average person is also able to be tested through a blood draw.

TEST RATHER THAN GUESS

Because there are various root causes for mental health disorders, it is important to test for which are most likely in any given case. At the Medicine with Heart clinic so we can drill down to the precise root cause(s) and not waste time with treatments that are not relevant. There are some standard tests that we can do to identify the different infections that may contribute to mental health.

LYME & CO-INFECTIONS TESTING:

● The Western blot blood test is currently the gold standard test to help identify a Borrelia or other co-infection. With this test, we can see if someone has Lyme disease or a Lyme co-infection.

● There are several specialty labs offer good testing for Lyme and co-infections antibodies and PCR tests

● Vibrant Wellness, iGenex, and DNA Connexions all have good test options

● While not a “co-infection”, strep antibodies can be tested through large labs like LabCorp and Quest and Bioreference

MOLD TOXIN TESTING:

● There are several tests that can be done to check for mold illness

● One test that is easy to do online is the VCS or Visual Contrast Sensitivity test. It screens for mold illness and patients can do it online. It is also a useful test to check progress during mold illness treatment. It is also relevant for infections like Lyme, co-infections, and COVID-19.

● There are also certain blood markers that can be tested in a lab to check for mold illness. These include TGF Beta-1, MMP-9, MSH, and C4a as some of the main markers affected by mold toxin accumulation. We can also check for the genetic susceptibility to mold illness by testing for a particular segment of the HLA gene called HLA DR1/3/4/5 DQ, Intermediate Resolution. These markers can be ordered through LabCorp and/or Quest.

● Mycotoxins can be directly measured in the urine (called urinary mycotoxins) and are available through Vibrant Wellness, Great Plains, and Realtime Labs.

VIRUS TESTING:

● Antibodies to viruses such as Epstein-Barr Virus (EBV), herpes viruses such as HSV1, HSV2, and HHV6, cytomegalovirus, and others. There is some nuance to IgG vs IgM, early antigen in the case of EBV, and other considerations beyond the scope of this book. Please work with a knowledgeable provider who is experienced with latent and chronic viral infections. Many doctors are still of a mentality that latent viral infections are not a significant impact to physical or mental health.

● Neopterin is a more general marker that may be elevated by viral load (also can be impacted by Lyme, helicobacter pylori, and parasites)

BRAIN AUTOANTIBODY TESTING:

● Testing has been developed for looking for antibodies against brain tissue

● While infections or toxins may be the causes of brain antibody elevation, evaluation of brain antibodies allows a check and balance to make sure that underlying triggers are being adequately addressed

● If neurological / brain antibodies are elevated and infections or toxins are treated, antibodies can be re-tested to evaluate if they are decreasing and whether there are outstanding elevations

● This is important because other root causes such as gut dysbiosis or missed infections or other toxins may be playing a role

● Labs testing brain autoantibodies include Vibrant Wellness (Neural Zoomer Plus) and Moleculera (Cunningham Panel)

CHAPTER 6:

TREATMENT STRATEGIES FOR

INFECTIONS AND TOXINS

FUNCTIONAL MEDICINE TREATMENT STRATEGIES

This section offers general advice and is not specific to any single individual. Part of the brilliance of a skilled functional medicine professional is to be able to customize a treatment plan to the individual. This, together with appropriate re-testing, tracking progress, and adjusting the care plan throughout the course of treatment are all important elements that cannot be covered in the context of a book like this. As such, please take treatment advice with a grain of salt and seek professional help whenever possible. Find a skilled practitioner experienced with labs listed in the previous section. If you would like to find out more about working with the Medicine with Heart clinic, please visit https://medicinewithheart.com/discovery-consultation where you can book a complimentary discovery consultation with staff.

GENERAL TREATMENT FOR LYME, CO-INFECTIONS, MOLD AND VIRAL INFECTION

With any chronic infection, it is important to strengthen the body, the immune system and to improve the terrain, i.e., the strength and resilience of the body. Because one of the common underpinnings of mental illness is inflammation, identifying the sources of chronic and systemic inflammation while reducing the inflammatory burden is important. There are several general strategies you can employ to do this.

It is also important to target and kill off the specific pathogens that may have become chronic and may be triggering brain autoantibodies and continual inflammation. There are different ways to achieve this. Some treatment strategies that Dr Miles and the Medicine with Heart clinic have found effective are outlined below.

TREATMENT FOR LYME DISEASE

This could be its own book. Lyme is both complicated and virulent. Lyme persister cells can survive antibiotics in a petri dish and then regrow a few weeks later. Only one herb has shown to eradicate Lyme in its mobile, stationary, and likely persister cell form (it did not regrow in the petri dish after applying the herb at sufficient doses). This herb is called cryptolepis and is a rare African herb. Dr Miles has designed a formulation containing cryptolepis in a synergistic formulation with other helpful herbs in a formula called “Resolve the Hidden” available through Goldenflower Herbs. However, this is a powerful formulation and the herbal line is a practitioner-only line for this reason. Please ask your provider about considering utilizing this formulation if you are drawn to it.

Some pharmaceutical medications such as dapsone may also work on persister cells. One small clinical trial for patients struggling with Chronic Lyme Disease found when antimicrobials were combined together with dapsone at a dose of 100mg twice per day for about 7-8 weeks (called Double-Dose Dapsone Combination Therapy), found that 98% of the 40 patients analyzed improved with 45% remaining with remission of symptoms for 1 year or longer (Horowitz, 2020).26

Another dapsone trial was performed with an even higher dose for a shorter time. This study gave Short-Term High Dose Pulsed Dapsone Combination Therapy combining antimicrobials with 200mg daily for 3-4 days and/or 200mg twice daily of dapsone for 4 days. Most of these patients had persistent symptoms even after multiple rounds of double dapsone and so this higher dose pulsed therapy was trialed. A majority of

26 Horowitz RI, Freeman PR. Efficacy of Double-Dose Dapsone Combination Therapy in the Treatment of Chronic Lyme Disease/Post-Treatment Lyme Disease Syndrome (PTLDS) and Associated Co-infections: A Report of Three Cases and Retrospective Chart Review Antibiotics (Basel) 2020;9(11):725. Published 2020 Oct 22. doi:10.3390/antibiotics9110725

patients in this group experienced sustained improvement in eight major symptoms: fatigue, pain, headaches, neuropathy, insomnia, cognition, and sweating (Horowitz, 2022).

27 Additionally, several other herbs and/or antibiotics are important for working with the Lyme infection, biofilm, immune function and regulation, and neurological systems. These are addressed in another two formulations called “Clear the Hidden 1” and “Clear the Hidden 2” also available through Goldenflower Herbs.

Beyond antimicrobials and persister cell herbs or drugs, most people struggling with Lyme also need to assess for and address nutrient deficiencies as there can be significant gut dysbiosis and malabsorption. Additionally, mitochondrial antioxidant defense is often overburdened and mitochondrial and antioxidative support is helpful. The nuances and details of this are quite complex and beyond the scope of this book. However, make sure that you are addressing nutrients, immune system regulation, gut dysbiosis, and mitochondrial function if you are working on Lyme. Also, methylation is important to assess and if homocysteine is elevated above 8 µmol/l often support for methylation is helpful.

Due to the complexity of working with Lyme disease, it is not recommended to go it alone. Please find a skilled provider to work with.

27 Horowitz RI, Freeman PR. Efficacy of Short-Term High Dose Pulsed Dapsone Combination Therapy in the Treatment of Chronic Lyme Disease/Post-Treatment Lyme Disease Syndrome (PTLDS) and Associated Co-Infections: A Report of Three Cases and Literature Review Antibiotics (Basel) 2022;11(7):912. Published 2022 Jul 7. doi:10.3390/antibiotics11070912

TREATMENT FOR LYME CO-INFECTION

These are very similar to Lyme. There are some commonalities in treatment and Lyme treatment may take care of some of the co-infections. However, infections like bartonella for example can be quite challenging both to test for and to treat. Some people find benefit from adding methylene blue to a protocol for bartonella.

For babesia, cryptolepis has shown efficacy along with Chinese skullcap. Additionally, oil of oregano may be helpful at high doses although should be done under the supervision of a provider. Several other herbals and pharmaceuticals can be used.

All the ancillary elements like nutrients, gut dysbiosis, biofilm, mitochondrial function, and methylation also apply for co-infections.

TREATMENT FOR MOLD ILLNESS

This, like Lyme and co-infections, is incredibly complex and challenging to effectively treat. There is often a multi-step approach that can take 1-2 years. If lab evidence of mycotoxin bioaccumulation is present, it is important to evaluate the home and workplace for mold. This alone can be challenging as no test is perfect and no inspection is foolproof. If toxic mold is found, the environment must be thoroughly remediated or left in most cases. There are a few exceptions to this with more modest levels and significant brain retraining work, but remediation or leaving is the general rule of thumb. This can be a big step and involves nuances related to possessions and which can harbor spores and what to do about that.

Once exposure is minimized, then removing the accumulated toxin from tissue becomes the focus. Binders like zeolite clay, activated charcoal, chlorella, and/or

Welchol or Cholestyramine (if using a pharmaceutical drug) can be used to bind and remove the mold toxins. Because binders can deplete B vitamins and minerals, supplementing these can be helpful. Also phosphatidylcholine, butyrate, saccharomyces boulardii, NAC, glutathione, r-lipoic acid, and many other nutraceuticals can be helpful in this process. It is important to upregulate phases I and II of liver detoxification, activate the Nrf-2 transcription factor, upregulate the MRP2 protein for bile formation and flow, and many other things which are beyond the scope of this book.

Additionally, a sinus swab for a multiple antibiotic resistant coagulative negative staph (MARCoNS) is important to test for and treat if present. This can form biofilm in the sinuses and contribute to neurological symptoms, chronic sinus infections, and may be linked to amyloid plaque in the brain and cognitive decline.

Then repair to the brain and hormone systems are important once the burden of toxin has lowered and the sinuses are free of biofilm-forming bacteria. This is achieved with peptides and nutrients that support tissue repair. This phase alone takes about 6 months for being able to restore brain and body function.

TREATMENT FOR VIRUSES

Viral infections that become chronic or reactivate tend to be what is sometimes referred to as “opportunistic” meaning they take advantage of a lowered immune responsiveness. Other infections, toxic burden, gut dysfunction, and significant levels of stress may all play a role in viral infections. Thus, it is not an effective strategy to simply take anti-viral drugs or herbs. Instead, focusing on immune system support and regulation together with evaluating for nutrient deficiencies, gut dysfunction,

mitochondrial issues, methylation imbalance, and other infections becomes important. Optimizing levels of fat-soluble vitamins such as Vitamins A, D, and K2 can be quite helpful. Additionally, making sure that zinc, copper, and magnesium levels are sufficient can make a big difference as well. Some herbs like elderberry and andrographis and some medicinal mushrooms like reishi and cordyceps may help with viral infections and immune regulation as well.

Because of the challenges in dealing with all the underlying factors of chronic viral infections, it is important to find good tracking markers like neopterin (if elevated) and see how it is responding to treatments. The VCS test can also help with tracking visual system and symptom changes with the questionnaires that it includes.

NATURAL APPROACHES TO TREATMENT

In conjunction with microbe / toxin specific treatment, adopting a broader spectrum of natural approaches that fight inflammation, support the immune system, and allow the body to come back into balance can support mental health.

AN ANTI-INFLAMMATORY DIET

Inflammation in the body can be reduced through diet. Some respond well to Paleo diet and others a gluten-free Mediterranean diet which both boast anti-inflammatory properties. A high sugar diet, and the resultant blood sugar dysregulation, is especially unhelpful for issues like anxiety. We recommend a blood sugar-balancing diet to enhance mood. Both the Paleo and gluten-free Mediterranean diet are good for blood sugar regulation as well. In some cases, doing an elimination diet process such as the Autoimmune Protocol diet for about 60 days followed by reintroduction of some foods can be extremely effective.

GOOD SLEEP HYGIENE AND HABITS

Sleep is critical for the body. There are many things you can do to make sure you get a good night’s sleep, every night. Avoid evening screen time, enhance your melatonin (the sleep hormone) production, have a calming routine and trouble-shoot any issues that may be causing insomnia are just a few things we can help you with. Additionally, it can help to reduce blue or bright lights after dark and adjust to the temperature where you sleep the best (research suggests for most people this is between 60-67 degrees Fahrenheit for ambient room temperature).

GENTLE EXERCISE AS APPROPRIATE

Movement and exercise are critical to our health. It is important to find a way that works for you to incorporate movement into your daily life. In some cases where people have debilitating mold illness or Lyme Disease, it becomes important to prudently avoid overdoing it or exercise beyond a level you can recover from before exercising the next time. Work with us to find out the appropriate amount of movement and exercise for your situation and challenge yourself to increase your movement incrementally and in a step-by-step fashion. Make sure to feel recovered from exercise before adding more frequent sessions or increasing intensity. Sometimes starting with walking and gentle movement systems like tai chi or qigong can be a great place to begin. Working towards short periods of high intensity interval training or weight training and some zone 2 exercise over time can be quite helpful and is important for the long run.

NATURE

Getting out into actually has data and science to show improvements in stress hormones and benefits for nervous system regulation. Forest bathing is a Japanese phenomenon whereby participants enhance their mood and health by walking through the forest. A systematic review and meta-analysis on forest bathing found significant reductions in the stress hormone cortisol (Antonelli M, 2019).28 Mountains, the sea, and any green natural space has the same effect so get outside and enjoy the fresh air and natural beaty.

28 Antonelli M, Barbieri G, Donelli D. Effects of forest bathing (shinrin-yoku) on levels of cortisol as a stress biomarker: a systematic review and meta-analysis. Int J Biometeorol 2019;63(8):1117-1134. doi:10.1007/s00484-019-01717-x

BREATHING

There are many breathing techniques that can help calm the nervous system and the mind. Breathing techniques are recommended for anyone with mental health struggles but can be especially helpful in an acute state of anxiety or panic.

Because inflammation underpins brain autoimmunity and neuroinflammation, anything that can significantly and reliably lower inflammation may be helpful for mental health. There have been multiple clinical trials on a breathing method that has shown to lower inflammatory markers and increase an anti-inflammatory protein compared with controls when injected with endotoxin. Thousands of participants have been injected with dead e-coli bacteria which have lipopolysaccharide (LPS) in the cell well. LPS is an endotoxin and when it is injected into the bloodstream it reliably triggers significant inflammation and severe symptoms. Until this landmark study, just about every participant had significant elevations in inflammatory markers and highly unpleasant symptoms for a few hours until the body clears the endotoxin from the blood.

Participants doing the Wim Hof Method breathing technique were injected with endotoxin and had significantly lower pro-inflammatory cytokines including IL-6, IL-2, TNF-alpha with a net reduction in inflammation compared to controls who were not doing the breathing of between 30-50%. Additionally, the anti-inflammatory protein IL-10 was between 44-194% higher in the breathing group versus control. (Zwaag, 2022)29 and (Knox M, 2014)30

29 Zwaag J, Naaktgeboren R, van Herwaarden AE, Pickkers P, Kox M. The Effects of Cold Exposure Training and a Breathing Exercise on the Inflammatory Response in Humans: A Pilot Study Psychosom Med 2022;84(4):457-467. doi:10.1097/PSY.0000000000001065

30 Kox M, van Eijk LT, Zwaag J, et al. Voluntary activation of the sympathetic nervous system and attenuation of the innate immune response in humans. Proc Natl Acad Sci U S A 2014;111(20):7379-7384. doi:10.1073/pnas.1322174111

Additionally, RMIT University conducted a survey of over 3,200 people all over the world about their experience with the Wim Hof Method. The reported positive outcomes that were most significant included more energy, better mood, and increased mental focus. The most significant medical conditions that showed improvement were stress, fatigue, anxiety, and depression.

For more about the Wim Hof Method breathing and other practices, there is an app called Wim Hof Method and the website is https://wimhofmethod.com

MEDITATION AND BRAIN RETRAINING

Meditation has shown benefit in research for stress reduction, anxiety, depression, and pain improvement (Brandmeyer T, 2019).31 While meditation has shown beneficial, it may take some time for it to make a noticeable impact. One study took non-experienced meditators and compared daily meditation for 13 minutes to 13 minutes of podcast listening. At the 8 but not 4-week mark, the meditation group reported decreased negative mood, enhanced attention, improved memory, and less anxiety compared to the podcast group (Basso J, 2019).32 This suggests that meditation can be effective at relatively short duration daily practices, but it may take a couple of months before noticing significant benefit. One of the biggest struggles that we see at the Medicine with Heart clinic is that people have a hard time budgeting daily time towards meditation practice on a consistent basis. This leads many to think it doesn’t work or they tried it and have not noticed the level of benefit they would like. Many of the benefits of meditation take time and consistent

31 Brandmeyer T, Delorme A, Wahbeh H. The neuroscience of meditation: classification, phenomenology, correlates, and mechanisms. Prog Brain Res. 2019;244:1-29. doi:10.1016/bs.pbr.2018.10.020

32 Basso JC, McHale A, Ende V, Oberlin DJ, Suzuki WA. Brief, daily meditation enhances attention, memory, mood, and emotional regulation in non-experienced meditators. Behav Brain Res 2019;356:208-220. doi:10.1016/j.bbr.2018.08.023

practice to develop. However, for those who commit themselves to daily practice with a minimum threshold of about 13 or more minutes often do notice significant benefits beginning in a couple of months time. Those who meditate for years often report continued and progressive benefits throughout the time they have been practicing.

Brain retraining practices are cognitive and/or somatic therapies intended to regulate the limbic system and trauma or fear response. When struggling with chronic illness, there are often hardships that are endured. Sometimes other people seem to have an easier time and often life feels unjust or dauntingly challenging. The experience of living with mental illness or chronic disease can take its own toll and that can compound frustration and sometimes even despair or hopelessness on top of the underlying condition. Brain retraining practices can help to desensitize the negative emotional response to the challenges and struggles of life and help to cultivate a fundamentally different way of relating to stress. Through self-awareness, cognitive reframing, somatic body-based awareness practices, and applied gratitude, there can be a shift to a more loving way of relating to the issues that arise in one’s experience.

REDUCE TOXIN EXPOSURE

One of the best ways to detoxify is to reduce the exposure to toxins. This allows the bodies detoxification processes to be less burdened and can often lead to significant reductions in inflammation and improvements in energy and mental clarity. You can start by identifying and minimizing exposure to sources of toxins like chemicals, pesticides in food, many cleaning products and cosmetics. Utilize resources such as the Environmental Working Group (EWG) for education about how to read labels and identify potentially toxic ingredients (https://ewg.org). Get help to cut out toxicants like excessive alcohol or cigarettes.

Mold toxins (aka mycotoxins) are more common than a lot of people realize. Just because you don’t see mold doesn’t mean it is not there. Check for signs of water damage such as discoloration or peeling under sinks, in bathrooms, in attic or crawl spaces, in basements, in the furnace room, and around appliances that have water running to them like refrigerators and dishwashers. If you had a history of past water damage which is no longer an issue, ask to find out if all water damaged porous materials such as dry wall, unfinished wood, insulation, carpeting, etc were actually removed and replaced. Drying out a porous material does not kill mold if it started to grow. Some mold can begin growing in as little as 24-48 hours. When a material is dried that already had some mold growing on it, the mold simply remains dormant. Once there is a sufficient level of humidity, it may begin to puff off spores again. This can lead to breathing in spores that have mycotoxin attached. These toxins are small enough that they can get through the lung barrier and into the bloodstream. For the genetically predisposed individuals who may have a more challenged immune system response to those mold toxins (about 1 in 4 people), the toxins may bioaccumulate in tissue. Sometimes that can be brain tissue and cause neuroinflammation and neurological symptoms as well as many other symptoms associated with chronic and systemic inflammation. Testing for and treating mold illness is challenging and it is best to work with an experienced practitioner when dealing with mold exposure. However, if you can prevent or reduce mold exposure to begin with, you are more likely to avoid what can be a debilitating illness for some.

Research and investigate some of the main signs for mold and inspect your home as best you can. Watch for sources of moisture, leaks, and signs of water damage. Promptly remove and replace water damaged porous materials if and when there are signs of water damage or leaks. If you suspect a history of water damage without being sure that materials were properly removed and replaced, take a dust sample and get a HERTSMI-2 or ERMI test to see what the spore counts are of some of the most toxic kinds of molds. If elevated, work to remediate the source or move. This

can be challenging and it is also helpful to have an experienced provider if you think your health has been challenged and an indoor air professional to help guide your process. Air filters can help reduce some toxicants in the air. They are not a substitute for dealing with water damage or mold, but they can help reduce allergens and pollutants and particulate in the air to an extent. Be sure to get an air purifier rated for your square feet (often multiple throughout the house). Also look for air purification systems that have HEPA filters and ideally a high grade of HEPA that filters out more than even standard HEPA.

Water filters are important for a variety of reasons. One is that even water in the US is a significant source of microplastics. In fact, the amount of microplastics ingested on average is estimated to be between 0.1-5g per week. An average credit card weighs about 5g. The largest source of microplastics are from water. While you might expect that bottled water would have microplastics if bottled in plastic, even tap water has been found in the US and other countries to contain a significant amount of microplastic fibers. Thus, water filtration is important but so too is minimizing water bottled in plastic even if filtered. This means that home filters such as the Berkey or Reverse Osmosis systems are effective ways to minimize microplastic consumption. Also other beverages made from water may have similar issues depending on where the water was sourced. This includes coffee, tea, alcohol, and bottled beverages of all kinds. It can be a tremendously worthwhile investment to get a good water filter and some stainless steel water bottles and bring filtered water with you when you go out. If you are traveling, there is a travel Berkey filter that some people will put in their suitcase and take with them. Also, there are some bottled water companies that do bottle filtered water directly into glass bottles.

IMPROVE GUT HEALTH

70-80% of immune cells reside in the gut. The gut truly is the foundation of our health. In addition to supporting immune health, a strong gut is important for brain health as well. The gut is linked to the brain through the ‘gut brain axis’. Gut health can directly impact conditions like anxiety or depression, autism, ADHD and many others. This occurs through multiple mechanisms. Intestinal permeability (aka “leaky gut”) can lead to bacteria from the gut getting into the bloodstream. Gram negative bacteria has lipopolysaccharide (LPS) in its cell wall and is considered an endotoxin. Increased endotoxin in the blood due to leaky gut can cause neuroinflammation and systemic inflammatory protein elevations.

Another mechanism for the gut impacting the brain is directly from the vagus nerve signals from the gut to the brain. It has been clearly demonstrated in research that signals from the brain to the gut are outweighed by signals from the gut to the brain. Changes in gut bacteria through for example probiotics in feed has demonstrated alterations in neurochemicals like GABA and improvements in stress resilience. While the vagus nerve innervates other organs and structures aside from the gut, studies have found that 80-90% of the fibers of the vagus nerve are linked to the gut.

Another mechanism is through gut bacteria production of peptidoglycans, a peptide compound that is important for brain development during childhood. In addition, this compound can be sensed by the brain and has been shown to reduce inflammation and increase anti-inflammatory markers. Also, clinical trials have shown reductions in stress and cortisol output as well as reduced mental fatigue and increased vitality

when dealing with social stress when using a probiotic strain high in peptidoglycans called bifidobacter longum 1714 (Wang H, 2019).33

When working with a skilled functional medicine practitioner, there are multiple labs that can be done to investigate gut dysfunction and treat the root causes. Examples of tests include Small Instestinal Bacterial Overgrowth (SIBO) 3-hour lactulose breath test and a comprehensive stool analysis. These two tests together can identify overgrown bacteria and pathogens that can cause intestinal permeability that can increase endotoxin and neuroinflammation. Also, LPS antibodies can be tested in the blood to see if there is likely a leaky gut leading to bacteria spilling into the blood. Additional testing such as food sensitivities and allergies plus blood antibodies against parietal cells in the stomach and gastrin levels can all add to the gut picture. With this testing there can be targeted treatments to reverse root causes and restore healthy function. Then polyphenolic compounds, bioflavonoids, probiotics, prebiotics, and omega fatty acids can all support maintaining a healthy gut and immune function once the background of dysbiosis, overgrowth, and pathogens have been removed.

REBALANCE HORMONES

Hormone imbalance can contribute to mood imbalances. It is well understood that progesterone levels and how soon and quickly they drop at the end of the menstrual cycle for a menstruating woman can impact mood significantly. If out of balance with estrogen or dropping too early, there can be significant mood changes that come towards the end of a cycle. Additionally, there may be a relationship to progesterone and estrogen ratio with other brain and cognitive issues like headaches, empathy, libido, ability to concentrate, and more. Testosterone impacts energy levels and sex

33 Wang H, Braun C, Murphy EF, Enck P Bifidobacterium longum 1714™ Strain Modulates Brain Activity of Healthy Volunteers During Social Stress. Am J Gastroenterol 2019;114(7):1152-1162. doi:10.14309/ajg.0000000000000203

drive which both can impact overall mood. Thyroid hormone has been shown to relate not only to metabolic function and weight, but also to gut motility and cognitive function. High dose thyroid hormone has been used for many years by some progressive psychiatrists for severe depression. Thus, testing for and addressing hormone imbalance can be an important part of working with mental health concerns. Sometimes bioidentical hormone replacement can make a world of difference for some people. Other times, working on root causes for hormone imbalances can lead to hormones naturally regulating without replacement. Many times infections, toxins, and gut issues when resolved yield greater hormone balance.

NEW THERAPIES

When mental and/or physical conditions become chronic, as is often the case in mental illness, we may need to do more. It is important to start with working on functional lab testing and treatments for infections, toxins, gut microbes, and hormones. It is also helpful to add breathwork, meditation, brain retraining, and exercise. Additionally implementing strategies to improve sleep, reduce inflammatory foods, and cultivate resilience in the face of stress. However, there are times when people have implemented much or all of the above and still feel off or stuck. Dr Miles has specialized in working with this kind of population and has found additional interventions that can help in these kinds of cases. However, there are many times when Dr Miles finds that there have been missed infections, toxins have not been fully addressed, or the repair process for building back the brain and hormone systems was not done sufficiently. So please focus on the basics first, then add functional lab testing and treatment as well as mind-body practices. Then after those things are established and worked through, some of the below novel therapies may be helpful.

There are all sorts of novel and effective treatment therapies available. Examples include light therapy or photobiomodulation which can help with depression and autoimmunity by reducing neuroinflammation (dos Santos Cardoso F, 2022)34 , phage therapy, peptides, magnetic therapy, PEMF devices, rife machines (frequency), sauna, plasmapheresis, and many more.

Phage therapy is a therapy that uses viruses to treat bacterial infections (Lin DM, 2017).35 It is not widely used nor well-known, primarily because not much research has been done with phage therapy. But it is a potential alternative to antibiotics in the case of bacterial infections. And it can be part of the solution for increasingly antibiotic-resistant bacteria.

Peptide therapy can be helpful for immune balance, neurological repair, and more. At the Medicine with Heart clinic peptides are often a part of the care plan at some point in time. They can produce strong signals for repairing the significant damage that has been done by infections and toxins.

These are just a few examples of new treatment therapies. It can be helpful to find a medical professional who is up to date on these novel therapies. Many doctors do not continue their education and cannot benefit from these new approaches. At the Medicine with Heart clinic, we closely follow new medical research and can use these therapies to help our patients as much as possible. You can follow some of the research by checking out our blog at https://medicinewithheart.com/blog

34 Cardoso FDS, Salehpour F, Coimbra NC, Gonzalez-Lima F, Gomes da Silva S. Photobiomodulation for the treatment of neuroinflammation: A systematic review of controlled laboratory animal studies. Front Neurosci. 2022;16:1006031. Published 2022 Sep 20. doi:10.3389/fnins.2022.1006031

35 Lin DM, Koskella B, Lin HC. Phage therapy: An alternative to antibiotics in the age of multi-drug resistance. World J Gastrointest Pharmacol Ther. 2017;8(3):162-173. doi:10.4292/wjgpt.v8.i3.162

Mental illness and other complex chronic disease have some similar underpinnings of inflammation and immune system dysfunction and nervous system dysregulation. It does not matter if the symptom picture is manifesting as depression, anxiety, chronic fatigue, pain, fibromyalgia, cognitive decline, brain fog, or something else. The manifestation can give clues towards one cause of why inflammation, immune, and nervous system issues have arisen. However, the main causes can be assessed for and evaluated based on symptom presentation, a thorough case history, and a targeted lab order based on your individual physiology and symptom cluster. The lab testing process is intended to identify the main root causes for which of the multivariable possibilities for things that can cause dysfunction in the system. Once the root causes are shown through testing and case history and questionnaires, a care plan can be developed that focuses on the few things that are the most likely to be contributing to the underling symptoms and dysfunction. The phase after testing tends to be removing the infection(s), improving gut function, and reducing exposure to toxins and improving detoxification. Then once the insults or injuries to the immune and nervous system have been sufficiently reduced, the repair process that is natural to the body kicks in. Additional nutraceuticals and peptides can also aid in and accelerate the repair phase. Then once the repair phase is complete, there are options to create a sustain and maintain plan or work towards optimization, longevity, and anti-aging.

THERE IS HOPE

Many factors influence and contribute to mental illness. Trauma, abuse, stress, genetics, psychosocial factors and gut health are just a few. But infections and toxins can be significant factors, with influence over the immune and inflammatory processes of the body. They are often missed and underappreciated in the picture of mental health testing and treatment options. Please take to heart the role of infections and toxins as significant and if you feel drawn to investigate them, find a skilled functional medicine professional who has experience working with infections and toxins as root causes for neuroinflammation and brain autoimmunity.

Any infectious condition that goes misdiagnosed or untreated has the potential to become more problematic over time. It can develop into a debilitating syndrome. With chronic conditions, delayed treatment can result in more severe disease. If you have chronic symptoms of unknown origin, there is hope. You can get in touch with a Functional Medicine clinic like Medicine with Heart (https://medicinewithheart.com) or search for a reputable and experienced clinician near you. Treating infections if present can in some cases reduce or resolve the onset or incidence of mental illness.

At the Medicine with Heart clinic, we have expertise in treating a range of complicated, difficult-to-diagnose conditions like Lyme, mold, chronic infection, stubborn digestive problems, thyroid issues, and autoimmune conditions. Our clinic has significant experience in looking for root causes to identify what could be perpetuating symptoms.

To find out more or set up a complimentary discovery consultation with staff at the Medicine with Heart clinic, please visit https://medicinewithheart.com or call or text 720-722-1143. Please reach out if you are seeking support with your health journey!

On behalf of Dr Miles and Medicine with Heart team, may you find a path towards dynamic health and an immense joyful and loving inner experience.

REFERENCES