Anti-basal ganglia antibodies in primary obsessive-compulsive disorder: systematic review and meta-analysis

Background Autoimmune-mediated basal ganglia dysfunction is implicated in the pathophysiology of neuropsychiatric disorders commonly manifesting with obsessive-compulsive features (e.g. Sydenham chorea). The relationship between autoimmunity and primary obsessive-compulsive disorder (OCD), however, is less clear. Aims To pool data on serum and cerebrospinal fluid (CSF) antibasal ganglia antibody (ABGA) positivity in primary OCD (without neurological or autoimmune comorbidity) relative to controls or neuropsychiatric disorders previously associated with increased odds of ABGA positivity. Method We performed electronic database and hand-searches for studies meeting pre-specified eligibility criteria from which we extracted data using a standardised form. We calculated pooled estimates of ABGA positivity using a random-effects model. Results Seven case-control studies totalling 844 participants met the eligibility criteria. Meta-analysis showed that a significantly greater proportion of those with primary OCD were ABGA seropositive compared with various controls (odds ratio (OR) = 4.97, 95% Cl 2.88-8.55, P<0.00001). This effect was not associated with heterogeneity or publication bias, and remained significant after stratifying the analysis by age, gender, disease severity, illness duration, immunostaining methodology, study quality, publication type, kind of control group, and sample size. There were no significant differences in ABGA seropositivrty for comparisons between primary OCD and Tourette syndrome, attention-deficit hyperactivity disorder or paediatric acute-onset neuropsychiatric syndrome. Results of one study testing CSF samples showed that a significantly greater proportion of participants with primary OCD were ABGA CSF-positive compared with healthy controls (OR=5.60, 95% Cl '1.04-30.20, P=0.045). Conclusions Odds of ABGA seropositivity are increased fivefold in primary OCD compared with controls, but are comparable to those associated with disorders previously associated with ABGA, providing circumstantial evidence of autoimmunity in a subset of those with primary OCO. Further experimental studies are needed to ascertain whether this relationship is causal.