# Anti-interneuron antibodies in abrupt-onset pediatric obsessive-compulsive disorder > **NIH NIH R21** · YALE UNIVERSITY · 2020 · $186,250 ## Abstract ABSTRACT Childhood-onset OCD is common, affecting 1-4% of youth, and causes profound morbidity. In some cases, symptom onset is remarkably rapid, even overnight. This striking presentation suggests a unique pathophysiology; the syndrome has been called ‘pediatric acute-onset neuropsychiatric disorder’, or PANS. Onset is often temporally associated with inflammatory illness, suggesting a neuroimmune mechanism, and immune-modulating treatments are sometimes used. However, pathophysiological details have been difficult to pin down, and the diagnostic landscape remains unclear. One specific etiopathophysiological hypothesis is that infectious illness can, in a susceptible host, lead to the production of antibodies cross-reactive with brain antigens. Consequent brain inflammation is proposed to produce neural dysfunction and clinical phenomenology; an analogy is sometimes drawn to Sydenham’s chorea, in which a similar antibody-mediated pathophysiology has been more clearly demonstrated. This proposal implies that there should be pathogenic antibodies in patients that are not found in controls. A number of studies have sought to characterize such antibodies, and reports have been published of antibodies reactive with D1R and D2R dopamine receptors, tubulin, and other antigens; but non-replication is common in this literature, and it remains unclear what antibodies, if any, contribute to disease. Identification of antibodies clearly associated with symptom onset or severity in PANS, or in any subset of PANS patients, would go far to clarify pathophysiology and diagnostic complexity in this population. With this goal in mind, we investigated antibody binding using a novel in vivo assay in mice. Rather than focusing on specific molecular targets, as most previous studies have done, we sought to examine cellular targets of illness-associated antibodies; and we did so in intact tissue, rather than in reduced systems. In recently published work we described elevated binding to cholinergic interneurons (CINs) in the striatum by antibodies from patients with pediatric autoimmune disorder associated with Streptococcus, or PANDAS, a narrower diagnosis related to PANS.9 CINS have previously been implicated in the pathophysiology of tic disorders and OCD, in post-mortem and preclinical work from our group and others. The suggestion that antibody binding to these interneurons may contribute to pathophysiology thus has immediate plausibility and merits further investigation. In unpublished pilot data we have reproduced this finding using a more efficient ex vivo assay and replicated it in a second small cohort of PANDAS patients. We now propose to replicate, refine, or refute the provocative finding from these pilot data by examining a larger cohort of patients. We will continue to focus on patients with PANDAS in order to limit clinical heterogeneity, but we will examine patients from three different clinical cohorts across two sites (NIMH and the Stanford PANS... ## Key facts - **NIH application ID:** 9916831 - **Project number:** 5R21MH119521-02 - **Recipient organization:** YALE UNIVERSITY - **Principal Investigator:** Christopher John Pittenger - **Activity code:** R21 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2020 - **Award amount:** $186,250 - **Award type:** 5 - **Project period:** 2019-04-16 → 2022-02-28 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/9916831 ## Citation > US National Institutes of Health, RePORTER application 9916831, Anti-interneuron antibodies in abrupt-onset pediatric obsessive-compulsive disorder (5R21MH119521-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9916831. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*