Microbes and Mental Illness

ILADS (International Lyme and Associated Diseases Society) is a group that has been presenting on the fundamentals of the controversy in diagnosing as well as treating patients who suffer chronic symptoms after brief conventional treatment for lyme or associated infections.

There are many different approaches that are presented, and over the years, there have been many repeat presenters who give their unique takes on what has worked for their specific patient population.

Dr Brian Fallon, a neuropsychiatrist, has given many nonantibiotic treatment options for lyme patients where antibiotics have not worked - and he is one of the main authors on the randomized control trial on IV antibiotic retreatment in chronic lyme. Others, such as Dr Horowitz, give a very comprehensive approach which includes supportive treatment, detoxification, as well as heavy coinfection treatment in his treatments, including combination drug approaches.

Dr Kenderlehrer has presented often as well, and his subset of patients have always seemed to be more sensitive. He has thus presented on more gentle, lower dose treatment options. There are often naturopathic compounds and principles that he seems to employ as well.

I saw with interest that he had a presentation in conjunction with Moleculara Labs in which he was describing relationships between infection and mental illness.

Background of how microbes may initiate or be an ongoing cause of mental illness

Chronic inflammation can cause the brain to become hypersensitive to stimuli. This is called central sensitivity syndrome, which can manifest as anxiety, depression, pain, fatigue, and many other symptoms.

Chronic infections will trigger the immune system as the body tries to clear the infection. In the case of a slow growing organisms, such as lyme, bartonella, the immune system activation may persist for a longer than usual period. Most other infections will resolve quite quickly without treatment.

When the immune system is chronically activated, there may be an imbalance of cytokines, such as an increase in mast cell activation, and an increase in microglial activation (the immune cells in the central nervous system).

Sometimes, antibodies against nerve cells (anti-neuronal antibodies) can develop (such as the ones measured by Moleculara Labs). This can lead to a type of post-infectious autoimmune encephelopathy.

Danish medical records study looking at infection and mental health

Dr Kenderlehrer reviewed a JAMA Psychiatry Danish Study conducted in 2019 by Kohler-Forsberg which revealed a compelling link between hospitalization for severe infection and a substantial increase of more than 80% in the risk of developing mental disorders. This study, involving one million patients, shed light on the interplay between infections and mental health.

There may be involvement of circulating autoantibodies as a potential mechanism. Exposure to infections triggers the production of antibodies, a crucial component of the immune response. However, in certain individuals, a phenomenon known as molecular mimicry may occur. In these cases, antibodies, rather than targeting the infecting agent, mistakenly attack receptors in the body, leading to a range of neuropsychiatric symptoms. Again, this may include antibodies against nerve cells. These symptoms encompass a spectrum from aggression and rage to obsessive-compulsive disorder (OCD) and anxiety.

Neuroinflammation is theorized to contribute in some other post infectious cases, such as long COVID

This mechanism has been particularly observed in conditions like long COVID, where individuals may experience persistent symptoms, and cross-reactive antibodies may target both cardiovascular and neurologic targets. Specific infections have shown a higher frequency of association with mental health issues, including group A strep, influenza A, mycoplasma, lyme, bartonella, babesia, and coxsackie virus. Notably, there is a sequence homology identified between the M protein in group A streptococcus and OSP A (outer surface protein A) in lyme.

Group A strep has a classic association with the production of autoantibodies and cross-reactivity, - we can sometimes see this in PANS and PANDAS patients in children. They have a sudden onset neuropsychiatric presentation with often OCD, and anxiety, after infection with strep.

Expanding beyond PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections) and PANS (Pediatric Acute-onset Neuropsychiatric Syndrome), the spectrum of autoimmune neuropsychiatric disorders associated with infections broadens considerably.

Dr. Katz, MD, has described ANDAL (Autoimmune Neuropsychiatric Disorder Associated with Lyme in Adults) as a notable manifestation of this complex relationship.

ANDAL specifically highlights the connection between Lyme disease and neuropsychiatric symptoms in adults. Lyme disease, caused by the bacterium Borrelia burgdorferi, can provoke an autoimmune response that targets the nervous system. This may result in a range of neuropsychiatric symptoms, including mood disorders, cognitive impairment, and behavioral changes.

Dr. Katz has presented previously on his experience in resistant adult patients, where low steady dose penicillin administered in the form of once weekly intramuscular injections was able to help when conventionally dosed antibiotics were not effective.

Autoimmune encephalopathy secondary to infection broadens the perspective, emphasizing that various infections, not limited to Lyme disease, can serve as catalysts for autoimmune reactions affecting the brain. This umbrella term encompasses scenarios where the body's immune system mistakenly attacks brain tissue, leading to a range of neuropsychiatric symptoms.

Distinguishing Infection-Triggered Autoimmune Neuropsychiatric Disorders and Traditional Psychiatric Etiologies

A possible approach to managing individuals with neuropsychiatric and behavioral disorders involves a subdivision to distinguish between those with infection-triggered autoimmune etiology and those with traditional psychiatric, social, or genetic etiologies. This categorization enables tailored treatment strategies.

For the subset with traditional psychiatric, social, or genetic etiologies, conventional psychotropic medications serve as a primary treatment modality. This approach aims to address symptoms through well-established pharmaceutical interventions such as antidepressant approaches, herbal approaches, and cognitive / behavioral interventions.

In contrast, for the subset with infection-triggered autoimmune etiology, a multifaceted therapeutic strategy may be necessary. Notably, the responsiveness to various interventions can guide treatment decisions:

1. Intravenous Immunoglobulin (IVIG):

   • Some individuals may exhibit positive responses to IVIG therapy. However, it's important to note that IVIG availability is usually only available at the recommendation of a neurologist. It is not commonly done in Canada though presenters at conferences at the states have discussed this.

2. Plasmapheresis:

   • Plasmapheresis, a procedure involving the removal, treatment, and return of blood plasma, has been another treatment discussed.. This method aims to eliminate harmful antibodies and other factors contributing to the autoimmune response. Again, availability is quite limited and I do not have direct experience with this methodology.

3. Steroids:

   • Steroids, with their anti-inflammatory properties, may be employed to suppress the immune system's hyperactivity and mitigate autoimmune reactions affecting the nervous system. Caution is needed if active infection is suspected, but I have not seen this to be an absolute contraindication.

4. Antibiotics:

   • In cases where infections are identified as triggers, targeted antibiotic therapy can be trialed if ongoing infection is suspected. While there is no perfect test, in conditions such as lyme testing can help to get an idea of the likelihood of benefit, in order to weigh against significant risk (if drug approaches are used). The responsiveness to these interventions varies among individuals, necessitating a personalized and adaptive treatment approach.

Genes may play a role in who is susceptible to post infection chronic symptoms

There may be relevance of genetic factors in susceptibility to cross-reactivity, emphasizing in some cases the importance of investigating the major histocompatibility complex (MHC) and human leukocyte antigen (HLA). Family history, particularly concerning autoimmune diseases, may hint at an individual's predisposition to these interactions between infections and mental health.

I do not often test for genetic susceptibility as it does not seem to affect treatment options and is quite costly. In some cases though, different testing that looks at methylation abnormalities can sometimes be useful.

It is important to note that not everyone who has the same exposure to a trigger (such as infection) will become ill in the same way. Largely susceptibility depends not only on these genetic factors but also other determinants of health such as nutrition, hormonal health, and other toxic burden.

Dr Kinderlehrer describes two categories of chronic lyme

1) Those with a known history of acute lyme, who have been treated with an antibiotic course but still have symptoms. These patients may have seen an embedded, engorged tick, and then subsequently developed a bulls eye rash; or have been in an endemic area, and then tested clearly positive for lyme.

2) Those who do not have prior knowledge of a tick-borne infection, but developed chronic symptoms and then have been subsequently diagnosed with this.

Dr Kinderlehrer described his experience that the second group outnumbers the first by 4-5.

Usually, patients in these categories could be more accurately described as having a lyme disease complex. This is because many, if not the majority, of patients have coinfections as well. This may include babesia, bartonella, mycoplasma, tick-borne relapsing fever, anasplasma, rickettsiosis, or infection with Powassan virus. Other co-morbidities are usually the rule, rather than the exception. Dr Kinderlehrer describes an interesting observation that in the states, the areas with the most moisture tend to have more problems with chronic lyme. There may be associations with mold problems in such cases. There is not published data that I could find that related to any associations between mold and chronic lyme susceptibility, but this is something that most practitioners have come across in increased frequency.

Things to consider with mental illness presentations

Anxiety and depression, prevalent in the general population, take on a distinctive character caused by infections. While these mental health challenges are widespread, a closer look reveals hints that may set apart infection-related psychiatric symptoms.

Common Ground: Anxiety and Depression Anxiety and depression are very common in the general population, and those with a more typical mental illness (not triggered by infection). There are some things that may hint that I would want to consider an inflammation, infectious, or post-infectious autoimmune link though:

Irritability and Rage Many of my patients with infection-related mental health symptoms will note an uncharacteristic irritability, and sometimes rage. This is not violent, but despite overwhelming fatigue and listlessness in other areas of their life, there seems to be energy to drive irritability as a background to cognitive fog, depression, and anxiety.

Unique Narratives: Dissociative Episodes Dissociative episodes are described by many - usually more a sense of "things not being real" or "not being present". Patients describe feeling like they are watching a movie or are in a half dream state much of the time.

Other Hints:

• Paradoxical Reactions to Psychotropic Medications:
  • Unusual responses to psychiatric medications may raise suspicion and prompt a deeper investigation into potential infectious origins.
• Early Onset Pre-Puberty:
  • Post infectious associated mental health symptoms may exhibit early onset, preceding puberty
• Absence of Personal/Family History
• New Onset Without Psychological Precipitants:
  • Cases where psychiatric symptoms manifest without clear psychological triggers point toward the possibility of an underlying infectious etiology.
• Peculiar Symptomatology:
  • A distinct profile emerges, particularly when psychological complaints coexist with multiple somatic symptoms. This symptom complex includes fatigue, headaches, joint and muscle pain, neuropathic pain, impaired cognition, and poor sleep.
• Overlapping Diagnoses:
  • Postinfectious mental health changes share common ground with other diagnoses and patients often have had other diagnoses such as Chronic Fatigue Syndrome (CFS), Fibromyalgia (FMS), autoimmune conditions with mood disorders, and the increasingly recognized mold mycotoxin illnesses.