Antineuronal antibodies in cerebrospinal fluid and serum of 104 patients with psychotic disorders compared to 104 individually matched healthy controls

Antineuronal antibodies can cause psychotic symptoms, particularly NMDAR antibodies; however, studies on the prevalence of antineuronal antibodies in cerebrospinal fluid (CSF) and serum of patients with psychotic disorders compared to matched healthy controls are sparse. We included 104 patients with a first-time diagnosis of a psychotic disorder within one year prior to inclusion (50 % outpatients) and 104 individually matched healthy controls, all without any known immunological conditions. CSF and serum were tested for IgG antibodies (Abs) against NMDAR NR1-subunit, GAD65, LGI1, CASPR2, AMPAR1, AMPAR2 and GABAb-receptor B1/B2 using commercial fixed cell-based assays (CBAs) (Euroimmun). Positive samples were retested with CBA twice, and tested with tissue-based assays (TBA). Primary outcomes were the presence of any of the seven anti-neuronal antibodies in CSF or serum. Secondarily, we analyzed the prevalence of each autoantibody. No antineuronal IgG antibodies were consistently found in any CSF sample and NMDAR-antibodies were not consistently present in any of the 208 participants, neither in CSF nor serum. CASPR2-Abs were consistently found in the serum of one patient and one control, and one healthy control, without diabetes, was seropositive for GAD65-Abs. CASPR2 borderline seropositivity was additionally found in one patient and two controls. All samples positive on CBA were negative on TBA. We found no significant differences between patients and controls. Antineuronal IgG antibodies are very rare when screening a broad group of individuals with recent-onset psychotic disorders without other indications of autoimmune encephalitis. Thus, much larger studies are needed to conclude on potential contrasts in prevalence compared to healthy controls.