top of page

The Overlooked Connection: Autoimmune Factors in Mental Health Disorders

Writer's picture: Rachel RothRachel Roth

For decades, mental health disorders such as schizophrenia and psychosis have been understood primarily through the lens of neurobiology and neurotransmitter imbalances. However, emerging research suggests a critical, often-overlooked factor: autoimmunity. Increasing evidence links immune dysfunction to psychiatric disorders, emphasizing the need for clinicians to consider autoimmune causes when diagnosing and treating severe mental illness.

The Immune Link: Schizophrenia and Autoimmunity

One of the most compelling findings in recent years is the genetic overlap between schizophrenia and multiple sclerosis (MS), both of which share risk loci in the major histocompatibility complex (MHC) region. This genetic connection suggests a fundamental link between immune regulation and psychiatric disorders. Furthermore, studies show that approximately 20% of patients with schizophrenia or psychosis exhibit inflammation in their cerebrospinal fluid (CSF), a strong indicator of immune system involvement in these conditions.

The Role of Inflammation in Psychiatric Disorders

In light of these findings, researchers have explored the potential of anti-inflammatory treatments for schizophrenia and psychosis. Unfortunately, broad-spectrum anti-inflammatory medications have not demonstrated significant clinical benefits. This suggests that a more targeted immunomodulatory approach may be necessary rather than a generalized reduction in inflammation.

Interestingly, when patients with clinical suspicion of autoimmune psychosis—despite having no detectable serum autoantibodies—were treated with immunomodulatory therapies, 80% experienced clinical improvement. This response rate underscores the importance of considering immune-mediated mechanisms in treatment-resistant psychiatric conditions.

COVID-19 and Increased Neuropsychiatric Risk

The COVID-19 pandemic has further highlighted the role of immune dysfunction in psychiatric disorders. Post-COVID syndromes include an increased incidence of neuropsychiatric conditions such as depression, anxiety, and even psychosis. The virus itself, as well as the immune response it triggers, appears to play a role in exacerbating or unmasking underlying autoimmune susceptibilities.

Clinical Implications: Rethinking Mental Health Diagnosis and Treatment

Given these findings, clinicians should maintain a high index of suspicion for autoimmune involvement in psychiatric disorders, particularly in cases that are resistant to conventional treatments. While routine serum autoantibody testing may not always be conclusive, a trial of immunomodulatory therapy in suspected cases may offer significant benefits.

Key Takeaways:

  • Schizophrenia and multiple sclerosis share genetic risk factors in the MHC region, highlighting a possible autoimmune component.

  • 20% of patients with schizophrenia/psychosis exhibit inflammation in the CSF, suggesting immune activation.

  • Broad anti-inflammatory treatments have shown limited efficacy, but targeted immunomodulation has led to significant improvement in suspected autoimmune psychosis cases.

  • Post-COVID patients are at increased risk for neuropsychiatric disorders, possibly due to immune dysregulation.

  • Clinicians should remain open to autoimmune etiologies in mental health disorders and consider treatment trials when clinical suspicion is high.

As research continues to evolve, integrating immunological perspectives into psychiatric care may open new therapeutic pathways for patients who have long struggled with treatment-resistant conditions. Keeping an open mind about autoimmune contributions to mental illness could transform outcomes for many individuals affected by these complex disorders.


Recommended papers:

Endres D, et al. Mol Psychiatry. 2022. PMID: 35046526

Endres D, Pollak TA, Bechter K, Denzel D, Pitsch K, Nickel K, Runge K, Pankratz B, Klatzmann D, Tamouza R, Mallet L, Leboyer M, Prüss H, Voderholzer U, Cunningham JL; ECNP Network Immuno-NeuroPsychiatry; Domschke K, Tebartz van Elst L, Schiele MA.

Transl Psychiatry. 2022 Jan 10;12(1):5. doi: 10.1038/s41398-021-01700-4.

Endres D, Maier V, Leypoldt F, Wandinger KP, Lennox B, Pollak TA, Nickel K, Maier S, Feige B, Domschke K, Prüss H, Bechter K, Dersch R, Tebartz van Elst L.

Psychol Med. 2022 Apr;52(6):1135-1146. doi: 10.1017/S0033291720002895. Epub 2020 Sep 7.

PMID: 32892761




3 views0 comments

Recent Posts

See All

Comments


Dr Ruth footer background
Let's Connect
Hours Of Service

Monday - Friday: 8:00am - 2:00pm est

Weekend appointments available

States Services Are Available:

New York, Florida, and Washington

Copyright © 2025, Dr Rachel Roth.  All rights reserved. Terms and Conditions | Privacy Policy
Website design by Ideas Company.

bottom of page