To determine the frequency and significance of neuronal surface antibodies (NS-Abs) in CSF and serum of patients with a first episode of psychosis (FEP).

Prospective assessment of symptoms, serum and CSF NS-Abs in patients with FEP admitted to two Psychiatry Services (Barcelona, Spain).

84 patients were included (median age, 32 years [IQR 23–45]), 39 (46%) female. Only two (2%) harbored CSF NMDAR-abs (1 also in serum). Both were women (26 and 48 year-old) without teratoma, transferred from other institutions, and with clinical presentations that readily suggested atypical psychosis. One developed insomnia, verbal auditory and musical hallucinations, abnormal behavior, and rapid progression to seizures and stupor requiring intensive care support. The other developed insomnia, olfactory hallucinations, echolalia, emotional lability, and stupor alternating with psychomotor agitation. Both had CSF pleocytosis and abnormal EEG (normal brain MRI), and dramatically responded to immunotherapy. Among the 82 NS-Ab-negative patients, 77 had clinical features considered typical of a primary psychotic disorder. 27/77 (35%) had one or more of the following neurologic symptoms: insomnia, headache, tremor, confusion, cognitive impairment, motor stereotypies, parkinsonism or pain (due to concomitant spine tuberculosis); all had normal CSF; 64 normal EEG (2 abnormal: 1 diffuse slowing, 1 bifrontal epileptiform discharges without seizures), and 57 normal MRI (19 abnormal: non-specific atrophy or ischemic changes). Two additional patients had atypical psychosis (new-onset seizures, dysautonomia, fluctuating catatonia or intolerance to antipsychotics); immunotherapy was ineffective in both. The remaining three patients had a non-psychiatric cause of psychosis (leukoencephalopathy, thyrotoxicosis, frontotemporal dementia).

Two (2%) of 84 patients with a FEP admitted to psychiatric centers had anti-NMDAR encephalitis. We did not find NS-Abs in CSF and serum of patients with other causes of psychosis.