Background: Despite advances in the understanding of narcolepsy, little information the on association between narcolepsy and psychosis is available, except for amphetamine-related psychotic reactions. Our case-control study aimed to compare clinical differences and analyze risk factors in children who developed narcolepsy with cataplexy (N-C), schizophrenia, and N-C followed by schizophrenia.

Methods: Three age- and gender-matched groups of children with N-C schizophrenia (study group), N-C (control group 1), and schizophrenia only (control group 2) were investigated. Subjects filled out sleep questionnaires, sleep diaries, and quality of life scales, followed by polysomnography (PSG), multiple sleep latency tests (MSLT), routine blood tests, HLA typing, genetic analysis of genes of interest, and psychiatric evaluation. The risk factors for schizophrenia also were analyzed.

Results: The study group was significantly overweight when measuring body mass index (BMI) (P=.016), at narcolepsy onset compared to control group 1, and the study group developed schizophrenia after a mean of 2.55±1.8 years. Compared to control group 2, psychotic symptoms were significantly more severe in the study group, with a higher frequency of depressive symptoms and acute ward hospitalization in 8 out of 10 of the subjects. They also had poorer long-term response to treatment, despite multiple treatment trials targeting their florid psychotic symptoms. All subjects with narcolepsy were HLA DQ B1(∗)0602 positive. The study group had a significantly higher frequency of DQ B1(∗)-03:01/06:02 (70%) than the two other groups, without any significant difference in HLA-DR typing, tumor necrosis factor α (TNF-α) levels, hypocretin (orexin) receptor 1 gene, HCRTR1, and the hypocretin (orexin) receptor 2 gene, HCRTR2, or blood infectious titers.

Conclusion: BMI and weight at onset of narcolepsy as well as a higher frequency of DQ B1(∗)-03:01/06:02 antigens were the only significant differences in the N-C children with secondary schizophrenia; such an association is a therapeutic challenge with long-term persistence of severe psychotic symptoms.