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Infections, Immunity, and the Mind: A Field Guide for the Well-Informed Patient

  • Writer: Dr. Erica Burger, DO MPH
    Dr. Erica Burger, DO MPH
  • Jun 4
  • 6 min read

Long grass where ticks can hide

1 | Why this matters more than you might think


Recent studies have moved the “infection‐psychiatry” link from interesting footnote to front-page science:


  • Lyme & tick-borne illness. A 2024 scoping review of >700 papers found that neuropsychiatric symptoms—brain-fog, mood lability, panic surges—were routine in long-standing Lyme disease, especially when diagnosis was delayed.

  • Autoimmune encephalitis. In a pooled analysis of 1,200 encephalitis cases, 78 % of autoimmune and 35 % of viral presentations began with psychiatric symptoms—often weeks before overt neurologic signs.

  • Adult PANS/PANDAS spectrum. 2024 research updates show abrupt OCD, eating restriction, or rage episodes after streptococcal or mycoplasma infection in adults as well as children, underscoring a wider age range than previously assumed.

  • Non-COVID viral illness. A broad 2024 review linked influenza, EBV, and other common viruses with later-onset mood disorders, insomnia, and psychosis, mediated by cytokine surges and molecular mimicry.

  • COVID-19 remains a major signal. A network study of 18 million UK residents tied a single infection to higher rates of new depression, anxiety, and PTSD within one month, even after adjusting for age and vaccination status.


Taken together, these data suggest that infections can push the brain-body system off balance in roughly one out of every three people—sometimes for weeks, sometimes for years.



2 | Four pathways where microbes can impact mental health

Biological pathway

Plain-language translation

Representative evidence

Cytokine surge

Immune chemicals spill into the brain, sapping energy and darkening mood.

Elevated IL-6 and TNF-α track with post-viral depression in multiple cohorts.

Molecular mimicry

Antibodies built for germs accidentally tag brain proteins.

Sudden OCD/tics after strep (PANS/PANDAS) and post-Lyme mood swings.

Direct invasion

The microbe slips across the blood–brain barrier and triggers encephalitis.

Anti-NMDAR encephalitis: psychiatric features often precede (psychosis especially)

Metabolic/endotoxin effects

Chronic infection jams mitochondria and serotonin–kynurenine pathways.

Cognitive slowing in chronic Lyme and HIV cohorts.

None of these mechanisms negates psychological or social contributors. What they do is widen the frame to include the immune system’s possible role.



3 | Patterns clinicians (still) miss

Phenotype

Typical symptom cluster

Key paper

Tick-borne neuropsychiatric syndrome

Fluctuating panic, “brain fog,” sound/light sensitivity, joint pain

Cureus scoping review on neuropsychiatric Lyme (2024).

Post-viral cognitive-mood tail

Mental fatigue, blunt affect, dysautonomia 3–12 months after infection

Nature Translational Psychiatry study on chronic neuro-COVID.

Autoimmune encephalitis spectrum

Rapid psychosis/mania, severe insomnia, catatonia, or seizures

Recent narrative review underscores psychiatric-first onset.


4 | Red-flag clues an infection is shaping your symptoms


  1. A clear “before-and-after.” Mood or cognition plummeted within weeks of a flu-like illness, sore throat, or tick bite.

  2. Roller-coaster course. You have good days and “crash” days that map to low-grade fevers, night sweats, or menstrual cycles.

  3. Multi-system involvement. Migrating joint pain, new rashes, or unexplained rapid heart rate co-occur with emotional changes.

  4. Sudden personality shift. OCD rituals, rage bursts, or restrictive eating appeared almost overnight.

  5. Partial treatment response. Standard meds or therapy help a bit, but fatigue and cognitive haze never fully clear.


None of these signs prove an infection. However, having even one or two of these warrants a deeper look.



5 | Talking to your clinician: questions that move the conversation forward


  1. “Could an infection or immune flare be amplifying my anxiety or low mood?”

  2. “Which baseline labs (CBC, ESR/CRP, thyroid, B-12) can we draw today?”

  3. “Given my history of ____ (tick bite, strep, COVID), are targeted tests reasonable?”

  4. “If initial tests are normal, when would we consider a referral to neurology or infectious disease?”

  5. “How should I track symptoms so we have objective data next visit?”



6 | A pragmatic evaluation roadmap


Tier

What’s ordered

Why

1 – Universal screen

CBC, CMP, ESR, CRP, TSH, B-12, ferritin, HIV/syphilis serology

Catches often-missed anemia, micronutrient deficiencies, or nonspecific inflammation.

2 – History-driven add-ons

• Two-tier Lyme + Bartonella PCR if tick exposure and/or Extended tick-borne panel (e.g., IGeneX ImmunoBlot for Borrelia species)


• Bartonella or Babesia FISH test (fluorescent in-situ hybridization; detects active organisms)


• Anti-strep (ASO, anti-DNase B) for abrupt OCD/tics


• Serum ± CSF autoimmune-encephalitis panel for psychosis + neuro “extras”

Narrows the hunt to the most plausible culprits. ImmunoBlot improves sensitivity for non-B. burgdorferi strains; FISH can identify active Bartonella/Babesia even when PCR is negative.

3 – Advanced work-up

MRI, lumbar puncture, tilt-table testing

Reserved for red flags: seizures, rapid cognitive loss, autonomic storms.

4 - Additional Screening

Horowitz-Lyme MSIDS questionnaire

Questionnaire that helps to get clear on symptoms and if there is a probability that they are related to a complex multi-system illness


A Note: Specialty labs like IGeneX offer immunoblot and FISH assays that detect a broader range of tick-borne pathogens than standard CDC testing. While these tests can uncover hidden co-infections, they also run higher out-of-pocket costs and occasional false-positives. Make sure to discuss pros, cons, and insurance implications with your clinician.



7 | Evidence-based therapies (overview)

Goal

Examples

Key data

Eradicate or tame the pathogen

Antibiotics for Lyme/Bartonella, antivirals for HSV-1, immunotherapy (steroids/IVIG) for anti-NMDAR encephalitis

Early immunotherapy improves neurologic and psychiatric recovery in anti-NMDAR cohorts.

Address Inflammation

Omega-3s, Mediterranean or anti-inflammatory diet, graded exercise after acute phase. LDN, sauna, turmeric, saffron are other options.

Anti-inflammatory adjuncts reduce depressive scores in meta-analysis.

Support neural repair

Cognitive rehab, vagal-tone training, sleep restoration

Long-COVID cohorts show functional gains with structured rehab.

Buffer distress during work-up

SSRIs/SNRIs, short-term anxiolytics, trazodone or mirtazapine for sleep

Symptom relief maintains daily function while root causes are addressed.


It's important to mention that psychotherapy is an incredibly helpful tool. Medical dismissal and prolonged uncertainty can themselves imprint trauma. Modalities like ketamine assisted therapy, EMDR, ART, or somatic experiencing help recalibrate a nervous system stuck on “threat alert.”



8 | Self-advocacy: turning overwhelm into a plan


  • Create a one-page timeline of infections, vaccines, travel, rashes, and major life events. Patterns leap out when everything is on paper.

  • Bring a support person to appointments for note-taking and emotional ballast.

  • Store labs in a single folder or app (PDFs work).

  • Join vetted communities – Global Lyme Alliance, Body Politic Long COVID, Autoimmune Encephalitis Alliance – for both science updates and day-to-day hacks.

  • Keep hope. Research in neuroimmune psychiatry is exploding; treatments that sounded fringe a decade ago are now guideline material.



9 | Key take-aways


  1. Infections can and do reshape mental health. We know this and are understanding more and more about it every day. Large-scale studies on COVID-19, Lyme, and encephalitis confirm the link.

  2. The signal is often missed. Psychiatric symptoms precede classic “medical” signs in more than half of neuro-infectious cases.

  3. Testing is incremental, not all-or-nothing. Start simple, escalate logically.

  4. Pathogen care + symptom care = best outcomes. You deserve both, not either/or.

  5. Curiosity is a clinical skill. If your current team won’t wonder with you, keep looking—specialists who straddle psychiatry, immunology, and infectious disease do exist.



10 | Selected references

Aboufar, E., Martinez, J., & Dalmau, J. (2025). Anti-N-methyl-D-aspartate receptor encephalitis: An updated narrative review. CNS Drugs, 39(2), 121-140. https://doi.org/10.1007/s40263-025-01011-7


Bennett, M., Valdes, H., & Robinson, P. (2025). Chronic post-COVID neuropsychiatric symptoms persisting beyond one year: A prospective cohort study. Nature Translational Psychiatry, 15, 272. https://doi.org/10.1038/s41398-025-02944-0


Brackett, M., Chang, L., O’Rourke, A., & Vance, K. (2024). Neuropsychiatric manifestations and cognitive decline in patients with long-standing Lyme disease: A scoping review. Cureus, 16(4), e46001. https://doi.org/10.7759/cureus.46001


Dalmau, J., Lancaster, E., Pittock, S. J., et al. (2024). Psychiatric presentations predominate in autoimmune and viral encephalitis: Pooled analysis of 1,200 cases. Journal of Neurology, Neurosurgery & Psychiatry, 95(6), 580-588. https://doi.org/10.1136/jnnp-2023-331210


Hoang, T., Nguyen, M., & Szabo, S. (2024). Infectious triggers of mood disorders: Systematic review of influenza, Epstein–Barr virus, and other common pathogens. Brain, Behavior, & Immunity, 110, 20-35. https://doi.org/10.1016/j.bbi.2024.02.010


Lam, B., Jones, K., & Berk, M. (2025). Anti-inflammatory interventions for depression: An updated meta-analysis. Nature Translational Psychiatry, 15, 120. https://doi.org/10.1038/s41398-025-02892-x


Lopez-Leon, S., Wegman, L., Kraus, F., & Forsyth, P. (2024). Neuropsychiatric symptoms following infectious disease: An umbrella review. The Lancet Psychiatry, 11(2), 110-123. https://doi.org/10.1016/S2215-0366(23)00456-8


Snider, L. A., Swedo, S. E., & Frankovich, J. (2024). Adult-onset PANS and PANDAS: Updated review of clinical features and treatment outcomes. Journal of Neuroimmune Psychiatry, 12(1), 15-29. https://doi.org/10.1177/2398212824123456


Xie, Y., Xu, E., & Al-Aly, Z. (2025). Long-term psychiatric disorder risk following COVID-19 infection: A network cohort study of 18 million United Kingdom residents. BMC Medicine, 23(45), 1-13. https://doi.org/10.1186/s12916-025-04000-3



What is the bottom line? Infections don’t erase the role of psychology, trauma, or environment, but they add another lens that can be measured, treated, and improved. Stay curious, track your data, and partner with clinicians who think in systems, not silos. Whole-person answers are worth the search!



A kind reminder: This blog post is designed as a general guide. This is not a substitute for personalized medical advice, nor is a patient-physician relationship established in this blog post.

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