Frequency and mechanisms underlying the association between
narcolepsy type 1 (NT1) and
psychosis remain unclear with potential role for a common immune pathway. We estimated the frequency of
psychosis and its characteristics in NT1 at two European sleep centers (France, n = 381; Spain, n = 161) and measured
IgG autoantibodies that recognize the GluN1 subunit of the NMDAR in 9 patients with NT1 with
psychosis, and 25 NT1 patients without
psychosis. Ten NT1 patients (6 in France, 4 in Spain) were diagnosed with comorbid
psychosis, a frequency of 1.8%. One patient reported psychotic symptoms few months before
narcolepsy onset, two patients few months after onset, and one patient one year after onset but after
modafinil introduction. The six remaining patients reported long delays between NT1 and
psychosis onset. Half the patients, mostly male adults, reported onset or worsening of psychotic symptoms after medication. We found no
IgG antibodies to NR1/NR2B heteromers of the NMDARs in patients with NT1 with or without
psychosis. To conclude,
psychosis is rare in NT1, with limited evidence for a key impact of stimulants, and no association with anti-NMDAR
antibodies. However, dramatic NT1 and
schizophrenia exists especially in early onset NT1, which may lead to inappropriate diagnosis and management.