Clinical, Neuroimmunologic, and CSF Investigations in First Episode Psychosis.

Objectives: To report the neuropsychiatric features and frequency of N-methyl-d-aspartate receptor (NMDAR) and other neuronal IgG antibodies in patients with first episode psychosis (FEP), and assess the performance of reported warning signs and criteria for autoimmune psychosis (AP). Methods: Prospective observational study of patients with FEP assessed for neuropsychiatric symptoms, serum and CSF neuronal antibodies (brain immunohistochemistry, cell-based assays, live neurons), and warning signs and criteria of AP. Previous autoimmune FEP series were reviewed. Findings: 105 patients were included; median age 30 years (range 14-75), 44 (42%) female. None had neuronal antibodies. Two/105 (2%) had CSF pleocytosis, 4/100 (4%) brain MRI abnormalities, and 3/73 (4%) EEG alterations. Thirty-four (32%) and 39 (37%) patients fulfilled two sets of warning signs of AP, and 21 (20%) fulfilled criteria of possible or probable AP, yet none developed AP. The cause of FEP was psychiatric in 101 (96%) and non-psychiatric in 4 (4%). During this study, 3 patients with psychosis caused by anti-NMDAR encephalitis were transferred to our center; 2 did not meet criteria for possible AP. Of 1159 reported FEP patients, only 7 (1%) had CSF studies; 36 (3%) had serum NMDAR-antibodies (without definite diagnosis of AP), and 4 had CSF NMDAR-antibodies (3 classic anti-NMDAR encephalitis and 1 with isolated psychiatric features). Conclusions: NMDAR-antibodies were not found in patients with FEP unless they had anti-NMDAR encephalitis. Warning signs and criteria for AP have limited utility when neurological symptoms are absent or paraclinical tests are normal. A diagnostic algorithm for autoimmune FEP is provided.