Dual Cases of Type 1 Narcolepsy with Schizophrenia and Other Psychotic Disorders

Abstract

Objective: Cases of narcolepsy in association with psychotic features have been reported but never fully characterized. These patients present diagnostic and treatment challenges and may shed new light on immune associations in schizophrenia. Method: Our case series was gathered at two narcolepsy specialty centers over a 9-year period. A questionnaire was created to improve diagnosis of schizophrenia or another psychotic disorder in patients with narcolepsy. Pathophysiological investigations included full HLA Class I and II typing, testing for known systemic and intracellular/synaptic neuronal antibodies, recently described neuronal surface antibodies, and immunocytochemistry on brain sections to detect new antigens. Results: Ten cases were identifi ed, one with schizoaffective disorder, one with delusional disorder, two with schizophreniform disorder, and 6 with schizophrenia. In all cases, narcolepsy manifested fi rst in childhood or adolescence, followed by psychotic symptoms after a variable interval. These patients had auditory hallucinations, which was the most differentiating clinical feature in comparison to narcolepsy patients without psychosis. Narcolepsy therapy may have played a role in triggering psychotic symptoms but these did not reverse with changes in narcolepsy medications. Response to antipsychotic treatment was variable. Pathophysiological studies did not reveal any known autoantibodies or unusual brain immunostaining pattern. No strong HLA association outside of HLA DQB1*06:02 was found, although increased DRB3*03 and DPA1*02:01 was notable. Conclusion: Narcolepsy can occur in association with schizophrenia, with signifi cant diagnostic and therapeutic challenges. Dual cases maybe under diagnosed, as onset is unusually early, often in childhood. Narcolepsy and psychosis may share an autoimmune pathology; thus, further investigations in larger samples are warranted. Keywords: type 1 narcolepsy, psychotic disorders, HLA, brain autoantibodies, autoimmune Citation: Canellas F, Lin L, Julià MR, Clemente A, VivesBauza C, Ollila HM, Hong SC, Arboleya SM, Einen MA, Faraco J, Fernandez-Vina M, Mignot E. Dual cases of type 1 narcolepsy with schizophrenia and other psychotic disorders. J Clin Sleep Med 2014;10(9):1011-1018. S C I E N T I F I C I N V E S T I G A T I O N ST ype 1 narcolepsy is a disabling sleep disorder caused by hypocretin-1 defi ciency affecting approximately 0.02% of adults worldwide.1 It is strongly associated with the DQB1*06:02 allele of the human leucocyte antigen (HLA) system, 2 and is likely due to an autoimmune attack causing a specifi c loss of hypothalamic hypocretin-1 neurons.Narcolepsy is characterized by the presence of daytime sleepiness, cataplectic attacks, hypnagogic/hypnopompic hallucinations, sleep paralysis, and disturbed nocturnal sleep. Initially narcolepsy was considered a psychiatric disorder, as some symptoms are reminiscent of psychiatric disorders, for instance, disordered thinking and confusion-like behaviors due to sleepiness; and psychotic-like symptoms d...

Anterior hippocampus volume loss in narcolepsy with cataplexy

“…An anterior hippocampal volume loss of 7% was found in male schizophrenia (Pegues, Rogers, Amend, Vinogradov, & Deicken, 2003). Narcolepsy can occur in association with schizophrenia (Canellas et al, 2014). Recent studies also suggest that antidepressants regulate behaviour by selectively increasing ventral hippocampal neurogenesis (Kheirbek & Hen, 2011).…”

Challenges in the development of therapeutics for narcolepsy

“…Psychotic disorders were not assessed in this study because there was no case in the matched general population sample. However, schizophrenia and other psychotic disorders have been noted to begin in children after the onset of narcolepsy (Canellas et al, 2014). The consequences of these medical and psychiatric comorbidities in narcolepsy may, at least in part, underlie the 1.5-fold increase in mortality observed in narcolepsy (Jennum et al, 2013; Ohayon et al, 2014).…”

Narcolepsia: o despertar para uma realidade subestimada

“…Era costumeiro considerar-se que uma verdadeira associação entre a narcolepsia e a E/OTP fosse muito rara ou devida a erros de diagnóstico. Essa realidade pode estar se transformando e, recentemente, em pacientes de Stanford e da Coreia do Sul, Canellas et al conseguiram identificar e estudar 10 casos em que havia a concomitância da narcolepsia e da E/OTP, sendo seis casos de esquizofrenia, dois do transtorno esquizofreniforme, um de transtorno delirante e um esquizoafetivo 45 . Essa associação se torna ainda mais interessante quando se tem em vista que, ultimamente, o sistema HLA, importante para a narcolepsia, também vem sendo considerado na esquizofrenia, em diversos genome wide analysis studies (GWAS) 46 .…”