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.

STAT3 and NTRK2 Genes Predicted by the Bioinformatics Approach May Play Important Roles in the Pathogenesis of Multiple Sclerosis and Obsessive–Compulsive Disorder

“…MS and OCD are highly genetic complaints that are assumed to share inherent risk factors. A review article by Enders et al proposed the ”autoimmune-OCD subtype” as it has been known that a subgroup of patients may have a secondary form of OCD with an organic cause and interestingly, autoimmune disorders are frequently associated with the secondary form of OCD [ 27 ]. To date, the identification of decisive vulnerability genes for these etiologically multifaceted disorders remains indefinable.…”

Immunopsychiatry – Innovative Technology to Characterize Disease Activity in Autoantibody-Associated Psychiatric Diseases

“…They suggest that these autoantibodies disturb the physiological processes by interacting with hypothalamic cells leading to augmented secretion of anorexigenic signaling ( 18 ). Another autoantibody category attracting considerable attention recently is anti-basal ganglia autoantibodies, believed to be pathogenically relevant for a subtype of obsessive compulsive disorder ( 2 , 19 ). As the basal ganglia play a key role in movement execution, anti-basal ganglia antibodies could play a pathogenic role in interfering with movement causing the repetitive behaviors and actions associated with obsessive compulsive disorder.…”

Changes in Volume of Subregions Within Basal Ganglia in Obsessive–Compulsive Disorder: A Study With Atlas-Based and VBM Methods

“…For example, the expression of dopamine D2 receptor decreased in the striatum (Nikolaus et al, 2010 ; Olver et al, 2010 ), and the knockout of glutamatergic gene SAPAP3 mainly expressed in striatum will lead to compulsive grooming behavior of mice (Burguière et al, 2013 ). Damage to the basal ganglia induced by antibodies can also lead to OCD (Endres et al, 2022 ). At the neural circuits level, the abnormality of basal ganglia activity leads to cognitive-affective dysfunction, which is manifested as the patients' negative interpretations of obsession that can result in compulsion (Schwartz, 1998 ).…”