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

Abstract

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.

Fig. 1. Autoimmune mediated secondary (organic) obsessive-compulsive syndromes [–, , –41, 44, 47, 48].

Abbreviations: CNS, central nervous system; OCD, obsessive-compulsive disorder.

Fig. 2. Exemplary findings suggestive of an autoimmune cause of obsessive-compulsive symptoms.

A The magnetic resonance imaging (MRI) shows multiple chronic inflammatory white matter lesions using FLAIR sequences. The corresponding patient was 22 years old at the time of the MRI, was diagnosed as neuropsychiatric lupus erythematosus and suffered from an atypical OCD with abrupt onset and additional psychotic symptoms. Immunotherapy with steroids, methotrexate and hydroxychloroquine resulted in an impressive clinical improvement [46] (online available at: https://www.frontiersin.org/articles/10.3389/fpsyt.2019.00226/full, retrieved on 30 January 2021; the reproduction was allowed by the publisher according to the Creative Commons Attribution License [CC BY]). B The [^18F]fluorodeoxyglucose positron emission tomography (FDG-PET) findings are from of an 18-year-old male patient with suspected PANDAS syndrome. Baseline images showed moderate to severe hypermetabolism of the left striatum. The cortex showed a hypometabolic signal. The metabolic changes disappeared completely after plasmapheresis treatment at 4 months follow-up [67] (online available at: https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-018-1063-y, retrieved on 30 January 2021; the reproduction was allowed by the publisher according to the Creative Commons Attribution 4.0 International License). C Intermittent rhythmic generalized electroencephalography (EEG) slowing in 41-year-old female patient with Hashimoto encephalopathy [129] (online available at: https://www.frontiersin.org/articles/10.3389/fpsyt.2017.00064/full, retrieved on 30 January 2021; the reproduction was allowed by the publisher according to the Creative Commons Attribution License [CC BY]). This EEG phenomenon is frequently found in patients with autoimmune psychiatric syndromes [75].

Fig. 3. The three main components in the treatment of autoimmune obsessive-compulsive disorders (cf. [, , –136]).

Abbreviations: OCD, obsessive-compulsive disorder; IVIGs, intravenous immunoglobulins; NSAID, non-steroidal anti-inflammatory drug; PLEX, plasmapheresis.