The Immune System’s Surprising Role in Catatonia
- Dr. Erica Burger, DO MPH
- 5 days ago
- 6 min read
Returning to the inpatient psychiatric and hospital medicine setting, I have re-familiarized myself with the nuances of diagnosing and working up the condition, catatonia. Catatonia, in short, is a state of altered consciousness and behavior, typically characterized by an individual's inability to move, speak as well as the pattern of getting "stuck" in body positions. There are many possible causes of catatonia. The treatment options are pretty straightforward, but the pathophysiology and underlying possible immune/infectious etiologies make this a condition requiring more careful thought and depth.
Prevalence of Catatonia
Catatonia is actually pretty common on the inpatient psychiatric unit, with a prevalence of 9-20% with the highest prevalence seen in those with bipolar disorder, depression, and/or schizophrenia. In fact, it's thought that up to 20% of manic patients have catatonia. In the general medical hospital, it is prevalent in 1.6 to 8.9% of patients who are hospitalized for medical reasons. It is often underdiagnosed and missed, since catatonia has a variable presentation and it's not always recognized that it can co-occur with common conditions such as delirium.
In children, those with neurodevelopmental disorders such as autism and genetic disorders are much more likely to develop catatonia. There isn't a tidy answer as to why but theories include metabolic abnormalities, having higher baseline immune activation in the brain (aka microglial activation), or having baseline imbalances in neurotransmitters.
Consequences of Catatonia
Why is it important that we diagnose and treat catatonia swiftly? People with catatonia have an increased risk of mortality and developing other medical issues such as malnutrition, dehydration, pulmonary embolisms, and aspiration. With malignant catatonia where vital signs become unstable, catatonia can be lethal. Therefore, catatonia should be considered in any patient with new onset motor activity abnormalities and peculiar behavior.
Diagnosis of Catatonia
Diagnosis of catatonia is based on a physical exam, observation, interview with the patient (or from friends/family of the patient), review of vital signs and oral intake. I also will check in with the nursing staff to listen to what they have observed in regards to the patient's behavior. This is important because the patient's presentation of catatonia can change over time. Psychiatrists most commonly utilize the Bush-Francis Catatonia Scale which serves as both a screening tool and is clinically validated for the diagnosing of catatonia. It can also be utilized to monitor treatment response.
Work Up of Catatonia
There are many different possible causes of catatonia. For each presentation of catatonia, a physical exam is essential. Additionally, one of the first tasks is assessing if catatonia is caused by substance use - either withdrawal from a prescription psychiatric medication such as clozapine or benzodiazepines, or withdrawal from cannabis or other drugs. Substance use-induced catatonia can also be due to drug intoxication.
Two-thirds of catatonia cases are caused by neurological causes such as encephalitis related to autoimmune or infectious causes, seizures, or a brain lesion. EEGs can help differentiate catatonia from delirium and can help assess for seizure activity. Additionally, brain MRIs tend to be more helpful than head CTs for assessing for inflammation, brain lesions, or brain swelling (associated with encephalitis). Lumbar punctures are indicated when there is concern for infectious or autoimmune causes of encephalitis, which can lead to catatonia. The key is to look for any reversible causes of catatonia which may demand different treatments.
Antipsychotic medications can trigger neuroleptic malignant syndrome (NMS) which is a common cause of malignant catatonia. Therefore, a careful review of medication history and assessing for symptoms consistent with NMS such as high body temperatures and unstable vital signs. Low serum iron levels are known to be more common in those with NMS so obtaining a serum iron lab can be useful.
Lab testing that can be high yield include serum iron, ESR, CRP, CBC, CMP, pro-calcitonin, d-dimer, and Creatine Kinase (CK) to assess for rhabdomyolysis. No single lab here will confirm infection, but can give clues into shifting the differential to an infectious cause. Patients are often not able to give a report of their symptoms so we often lean more into the physical exam, labs, and collateral.
Catatonia Treatment
The mainstay treatments for catatonia, regardless of the cause, include relatively high doses of lorazepam (a benzodiazepine) and/or electroconvulsive therapy (ECT). I am thankful to work in a hospital that still offers ECT, which is becoming more and more rare.
Lorazepam is also used to confirm catatonia - if someone responds to a 1-2 mg dose (usually given IV), we are on the right track and then we continue this treatment. While lorazepam is stated to be effective for 66-100% of those with catatonia, there are reasons why ECT may be recommended. If someone has more severe catatonia with unstable vital signs or lorazepam isn't effective, ECT is the gold standard. ECT is more effective than lorazepam and improves 88-100% of catatonia. These can be life-saving treatments.
Traditional teaching: think benzodiazepines, think ECT.
Emerging science: also think immune system.
The Immune System and Catatonia
Catatonia isn’t always rooted in psychiatry. Roughly one-fifth of cases begin with a medical trigger, most commonly an infection that reaches the nervous system. HSV, EBV, HIV, influenza, typhoid, malaria, and Lyme have all been reported. These pathogens release a surge of cytokines—IL-1β, IL-6, TNF-α—that can slow movement, mute speech, and push patients into the shut-down stance of classic “sickness behavior.” Treat the infection and catatonic features often recede, although many patients still need lorazepam or a course of ECT while the inflammation settles.
Two branches of immunity explain the pattern:
Innate immunity is the rapid-response team: neutrophils, macrophages, and cytokines that flood in within hours. If that response overshoots, motor circuits can stall, leaving the patient rigid or stuporous.
Adaptive immunity takes longer but is highly specific. B- and T-cells build antibodies aimed at particular targets. Problems arise when those antibodies mistake brain proteins—NMDA or GABA-A receptors—for threats. Receptor loss disrupts glutamate or GABA signalling and catatonia can appear even without fever or an elevated CRP. Autoimmune conditions such as Hashimoto encephalopathy, lupus, stiff-person spectrum, pernicious anemia, and pediatric PANDAS/PANS follow this script.
But here's the tricky part: The two immune systems often intersect. For example, viral encephalitis can trigger the innate response, expose neuronal antigens, and prompt a secondary antibody assault. A high neutrophil count and CRP point to an infectious, innate-driven picture that needs antimicrobials plus standard catatonia treatment of benzodiazepines +/- ECT.
The adaptive response can present later as a subacute course with seizures, autonomic swings, or sensitivity to tiny antipsychotic doses which is a compelling reason to pursue antibody testing and early immunotherapy treatment.
Treatment overlaps with immunity as well. Benzodiazepines, via GABA-A modulation, appear to dampen some inflammatory activity. ECT initially bumps cytokines but, over a full series, animal studies suggests a net anti-inflammatory effect.
A Note on Anti-NMDA Encephalitis
One autoimmune diagnosis we need to be aware of is anti-NMDA-receptor encephalitis—the poster child for antibody-driven catatonia. In this illness, B-cells churn out IgG that targets the GluN1 subunit of the NMDA receptor. Those antibodies internalise the receptor, shutting down glutamatergic signalling and short-circuiting cortical–subcortical loops that control movement and affect.
Clinically, anti-NMDA receptor encephalitis often starts off with anxiety, insomnia, or psychosis, then pivots to catatonia, seizures, and wild autonomic swings; a whopping two-thirds of NMDA-E patients develop catatonic features, and tiny doses of antipsychotics can push them straight into neuroleptic malignant syndrome (NMS).
CSF antibody testing is far more sensitive than serum, so a lumbar puncture is worth the effort if the presentation is suspicious. Treating the underlying immune dysfunction is essential. First-line treatment is immunotherapy—high-dose steroids, IVIG or plasmapheresis—followed by rituximab or cyclophosphamide for difficult cases. Add lorazepam or ECT as needed for motor symptoms, but without antibody clearance the catatonia is likely to return.
The Takeaway
Whenever catatonia presents, assess the immune angle. Deciding whether innate or adaptive processes dominate may determine whether the patient needs nothing more than lorazepam and/or ECT—or urgently requires antivirals, antibiotics, or high-dose steroids.
And a reminder that psychiatrists are trained in the intersection between medicine and psychiatry which includes the immune system, including infectious diseases and autoimmune conditions, and the intersection between the immune system and mental health symptoms.
Resources:
References:
Rogers, J. P., Pollak, T. A., Blackman, G., & David, A. S. (2019). Catatonia and the immune system: A review. The Lancet Psychiatry, 6(7), 620–630. https://doi.org/10.1016/S2215-0366(19)30142-8
Wilson, J. E., Oldham, M. A., Francis, A., Perkey, D., Kramer, E., Jiang, S., Yoon, J., Beach, S., Fricchione, G., Gunther, M., Ha, J., Luccarelli, J., Rosen, J., Hamlin, D., Dragonetti, J. D., Gerstenblith, A., Stewart, A. L., Sole, J., & Bourgeois, J. A. (2025). Catatonia: American Psychiatric Association Resource Document. Journal of the Academy of Consultation-Liaison Psychiatry. Advance online publication. https://doi.org/10.1016/j.jaclp.2025.05.001
Bush-Francis Catatonia Rating Scale Assessment Resources (includes standardized patient videos)
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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