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Immunological causes of obsessive-compulsive disorder: is it time for the concept of an "autoimmune OCD" subtype?

Research output: Contribution to journalReview articlepeer-review

ECNP Network Immuno-NeuroPsychiatry, Dominique Endres, Thomas A Pollak, Karl Bechter, Dominik Denzel, Karoline Pitsch, Kathrin Nickel, Kimon Runge, Benjamin Pankratz, David Klatzmann, Ryad Tamouza, Luc Mallet, Marion Leboyer, Harald Prüss, Ulrich Voderholzer, Janet L Cunningham, Katharina Domschke, Ludger Tebartz van Elst, Miriam A Schiele

Original languageEnglish
Article number5
Pages (from-to)5
JournalTranslational psychiatry
Issue number1
Early online date10 Jan 2022
Accepted/In press19 Oct 2021
E-pub ahead of print10 Jan 2022
PublishedDec 2022

Bibliographical note

Funding Information: DE was supported by the Berta-Ottenstein-Programme for Advanced Clinician Scientists, Faculty of Medicine, University of Freiburg. MAS was supported by the Medical-Scientist-Programme, Faculty of Medicine, University of Freiburg. MAS is a member of the Obsessive Compulsive and Related Disorders Network (OCRN) of the European College of Neuropsychopharmacology (ECNP). JLC was supported by a Gullstrand Fellowship, Uppsala University Hospital Uppsala Sweden. TP was supported by a NIHR Clinical Lectureship. Funding Information: The article processing charge was funded by the Baden-Wuerttemberg Ministry of Science, Research and Art and the University of Freiburg in the funding program Open Access Publishing. Open Access funding enabled and organized by Projekt DEAL Publisher Copyright: © 2021, The Author(s).

King's Authors


Obsessive-compulsive disorder (OCD) is a highly disabling mental illness that can be divided into frequent primary and rarer organic secondary forms. Its association with secondary autoimmune triggers was introduced through the discovery of Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infection (PANDAS) and Pediatric Acute onset Neuropsychiatric Syndrome (PANS). Autoimmune encephalitis and systemic autoimmune diseases or other autoimmune brain diseases, such as multiple sclerosis, have also been reported to sometimes present with obsessive-compulsive symptoms (OCS). Subgroups of patients with OCD show elevated proinflammatory cytokines and autoantibodies against targets that include the basal ganglia. In this conceptual review paper, the clinical manifestations, pathophysiological considerations, diagnostic investigations, and treatment approaches of immune-related secondary OCD are summarized. The novel concept of “autoimmune OCD” is proposed for a small subgroup of OCD patients, and clinical signs based on the PANDAS/PANS criteria and from recent experience with autoimmune encephalitis and autoimmune psychosis are suggested. Red flag signs for “autoimmune OCD” could include (sub)acute onset, unusual age of onset, atypical presentation of OCS with neuropsychiatric features (e.g., disproportionate cognitive deficits) or accompanying neurological symptoms (e.g., movement disorders), autonomic dysfunction, treatment resistance, associations of symptom onset with infections such as group A streptococcus, comorbid autoimmune diseases or malignancies. Clinical investigations may also reveal alterations such as increased levels of anti-basal ganglia or dopamine receptor antibodies or inflammatory changes in the basal ganglia in neuroimaging. Based on these red flag signs, the criteria for a possible, probable, and definite autoimmune OCD subtype are proposed.

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