Objective: Autoimmune encephalitis associated with autoantibodies against the N -methyl-d-aspartate receptor (NMDAR) often presents with behavioural change. Our objective was to describe in detail the psychiatric presentation and pathways to care in order to aid the early diagnosis of NMDAR encephalitis. Methods: Sera and cerebrospinal fluid (CSF) from patients with suspected NMDAR encephalitis were tested on HEK 293 cells transfected with the NR1 subunit of the NMDAR. Clinical information was obtained from the referring psychiatrists and neurologists and by review of the clinical records. Results: Samples from 15 patients (13 female, 2 male, mean age 24 years, range 5-56 years) tested anti-NMDAR positive. Twelve of the 15 patients (80%) presented with prominent psychiatric symptoms and 8 were initially referred to a psychiatric service. The most prominent initial psychiatric symptoms were anxiety in seven (47%), behavioural change (often bizarre) in six (40%) and agitation in five (33%). All patients developed psychiatric symptoms in the first 6 weeks of illness. Thirteen patients received psychotropic medications: antipsychotics in 12 and benzodiazepines in 11. Treating physicians considered the psychotropic medication not effective in 11 patients resulting in many drug switches. At nadir, all patients were in a very poor condition. However, eight patients (53%) recovered (almost) completely. Outcome tended to be better in patients who had received early immunotherapy or tumour removal. Conclusions: Autoimmune encephalitis and anti-NMDAR testing in serum and CSF should be considered in patients, especially young females, presenting with atypical psychiatric phenomena. Early diagnosis and treatment will likely improve the prognosis of NMDAR encephalitis. Significant outcomes• In this first Dutch cohort of patients with N -methyl-d-aspartate receptor (NMDAR) encephalitis, 80%presented with psychiatric symptoms while 62% were initially referred to a psychiatric service.• Apart from testing for anti-NMDAR antibodies in serum and/or cerebrospinal fluid (CSF) the most sensitive ancillary investigations were electroencephalography (EEG) (abnormal in 100% of tested patients), CSF routine examination (abnormal in 93%) and magnetic resonance imaging (MRI) (abnormal in 40%).• This study supports the idea that early recognition and treatment of NMDAR encephalitis results in better outcome.• Symptomatic antipsychotic therapy was generally ineffective on its own and required many drug switches until the inflammatory process was treated.

In a first study to compare subgroups of offenders with psychosis directly with non-psychotic offenders and non-offenders with psychosis, we found such additional support for a distinction between early and late starters with psychosis that different treatment strategies would seem indicated, focusing on personality and substance misuse for the former but psychotic symptoms for all. It remains to be seen whether the higher rate of alcohol misuse amongst late first offenders is a fundamental distinction or a function of age difference.