Lyme and other infections can trigger mental illness

A clear reminder that Lyme and other infections can trigger mental illness appears in two fresh studies. The first is a nationwide study conducted in Denmark and published in JAMA Psychiatry that focused on mental illness provoked by infections in children and adolescents. The authors note:

"Infections have been associated with increased risks for mental disorders, such as schizophrenia and depression. However, the association between all infections requiring treatment and the wide range of mental disorders is unknown to date."

To investigate this they examined data for all individuals born in Denmark between January 1, 1995, and June 30, 2012, 1,098 930 people, analyzing the association between all mental disorders diagnosed in a hospital setting and any redeemed prescription for psychotropic medication and all infections treated in and out of hospital.

Evidence for substantial risk of mental illness

Their study investigated not just Lyme disease but a wide range on infections. Antibiotic use was as a special hazard.

"Infections requiring hospitalizations were associated with subsequent increased risk of having a diagnosis of any mental disorder (n = 42 462) by an HRR of 1.84 (95% CI, 1.69-1.99) and with increased risk of redeeming a prescription for psychotropic medication (n = 56 847) by an HRR of 1.42 (95% CI, 1.37-1.46). Infection treated with anti-infective agents was associated with increased risk of having a diagnosis of any mental disorder (HRR, 1.40; 95% CI, 1.29-1.51) and with increased risk of redeeming a prescription for psychotropic medication (HRR, 1.22; 95% CI, 1.18-1.26)."

Moreover...

"Antibiotic use was associated with particularly increased risk estimates. The risk of mental disorders after infections increased in a dose-response association and with the temporal proximity of the last infection. In particular, schizophrenia spectrum disorders, obsessive-compulsive disorder, personality and behavior disorders, mental retardation, autistic spectrum disorder, attention-deficit/hyperactivity disorder, oppositional defiant disorder and conduct disorder, and tic disorders were associated with the highest risks after infections."

Rather than cast a shadow on the appropriate use of antibiotics it highlights two important points:

1. Antibiotics must be used with exquisite judgement and caution.
2. Modifying the microbiome can be therapeutic or catastrophic.

 The authors conclude:

"Although the results cannot prove causality, these findings provide evidence for the involvement of infections and the immune system in the etiology of a wide range of mental disorders in children and adolescents."

Both the immune response to the infection and/or antibiotic modulation of the microbiome can trigger an autoimmune inflammatory reaction that cross-reacts to brain and CNS antigens. 

Medscape also reports:

"Authors of an accompanying editorial note that the study provides "compelling epidemiologic evidence that severe infections, as well as exposure to anti-infective agents, are linked to the onset of neuropsychiatric illnesses in children."

Autoimmune post-treatment Lyme symptoms

Interesting research in the Journal of Neuroinflammation further confirms the role of autoimmunity in Lyme post-treatment neuropsychiatric disorders. Here, the authors used PET technology to visualize the overactive immune cells in the brain (microglia).

"The pathophysiology of post-treatment Lyme disease syndrome (PTLDS) may be linked to overactive immunity including aberrant activity of the brain’s resident immune cells, microglia. Here we used [¹¹C]DPA-713 and positron emission tomography to quantify the 18 kDa translocator protein, a marker of activated microglia or reactive astrocytes, in the brains of patients with post-treatment Lyme disease symptoms of any duration compared to healthy controls."

Because the mitochondrial 18 kDa translocator protein (TSPO) that is greatly increased in its expression by activated microglia and reactive astrocytes can be measured using radiotracers, positron emission tomography (PET), imaging TSPO is a useful method to test for immune activation in vivo in relevant neurological conditions.

CNS immune activation after Lyme

For all their subjects they confirmed a history of Lyme disease history and conducted a review of medical records, a clinical interview and battery of neuropsychological tests. Their TSPO-targeting second-generation radiotracers showed a definite difference between post-Lyme patients and controls.

"Our [¹¹C]DPA-713 PET data are consistent with higher levels of TSPO within eight brain regions among patients with persistent symptoms following treated Lyme disease compared to healthy controls and suggest the same pattern in other regions. These findings are in keeping with previously demonstrated evidence of circulating (serum) inflammatory markers in those with PTLDS or Lyme encephalopathy [6, 25] and uniquely support immune activation in the CNS in symptomatic patients with Lyme disease post-antibiotic treatment."

 Again we see the onset of neuropsychiatric symptoms due to an immune response to infection. The authors conclude:

"In summary, our results support the hypothesized role of CNS immune activation in patients with PTLDS. Further study of the relationship between higher glial activation in the CNS, systemic inflammatory signaling, and cognitive performance in PTLDS is needed."

Practical note: The Cunningham Panel from Moleculera Labs is a mainstay in autoimmunity testing for neuropsychiatric illnesses.