Inflammation, Obsessive-Compulsive Disorder, and Related Disorders

Initial reports supporting the possibility of inflammation in the brain in obsessive-compulsive disorder (OCD) evolved from the models of Sydenham's Chorea, and Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcus (PANDAS), which implicated excessive autoimmune responses following exposure to group A B-hemolytic streptococcal infections. Subsequently, this model was expanded to Pediatric Autoimmune Neuropsychiatric Syndrome (PANS) which applied the same concept but included other infections. A critical shortcoming of this model was that it was attributable to a small minority of OCD cases. The relationship between inflammation and OCD was more broadly demonstrated through translocator protein (TSPO) positron emission tomography imaging, a method that detects gliosis, an important component of brain inflammation, in neuropsychiatric diseases, including morphological activation and proliferation of microglia and to some extent astroglia. This method identified greater TSPO binding in the cortico-striatal-thalamo-cortical circuit in OCD, providing a direct brain measure of an important component of inflammation. To identify OCD cases with prominent elevations in TSPO binding in clinical research settings with lower cost peripheral markers, a promising approach is to apply blood serum biomarkers of inflammatory molecules produced by activated microglia and astroglia (gliosis). Such measures may aid stratification in future clinical trials. Several inflammatory-modifying interventions, including celecoxib, minocycline, and n-acetylcysteine, have been tested as treatments in randomized double-blind placebo controlled clinical trials and there is a tendency toward positive results, although these medications are not optimized for brain penetration and sample sizes for most trials were small. Future clinical trials of medications that target gliosis in OCD should apply larger sample sizes, ideally incorporating stratification approaches to enrich samples for the presence of gliosis.