Schizophrenia, narcolepsy, and HLA-DR15, DQ6

Abstract

A strong association between HLA-DR2, DQ1 and narcolepsy-cataplexy has been known since 1986. In 1990 a subdivision (HLA-DR15, DQ6) was shown to be equally associated. Narcolepsy symptoms include rapid eye movement (REM)-sleep intrusion hallucinations during the day. Some narcoleptics may be so hallucinated that they become delusional and receive a diagnosis of schizophrenia. Fifty-six inpatient schizophrenics and 56 normal controls were compared to see if there was an excess of the narcolepsy-associated antigens (NAA) among schizophrenics. Patients had frequency of the NAA 3.89 times higher than controls. After a subset was studied by night (n = 9) and day (n = 7) polysomnography, two patients were found to be true narcoleptics. Their psychosis improved with treatment for narcolepsy. When NAA(+) and NAA(-) schizophrenics were compared, the NAA(+) subgroup had significantly higher Brief Psychiatric Rating Scale (BPRS) scores and more hospitalizations. There were no effects attributable only to gender or race. We conclude that narcolepsy can simulate schizophrenia in some cases, and that even in nonnarcoleptic patients, the HLA-DR15,DQ6 antigens mark a group of severe schizophrenics that merits further study.

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

“…[15][16][17] There are also occasional reports of narcolepsy patients with challenging differential diagnoses with a psychotic disorder. 18,19 These highlight the difficulties faced by clinicians to correctly diagnose narcolepsy and psychosis in the presence of vivid hallucinations and altered behavior.…”

Narcoleptic and schizophrenic hallucinations

“…The other group of symptoms are so-called REM-associated symptoms and include sudden loss of times be difficult, particularly when hallucinations predominate [8,10,11,12,13]. However, the phenomenological similarities and differences of hallucinatory experiences in healthy controls, patients with psychotic disorders, and narcoleptic patients have so far not been investigated systematically.…”

Is Schizophrenia Associated with Narcolepsy?

“…16 However, as the above two cases illustrate, these disorders are not always readily dissociated, and their coexistence has been frequently reported. [5][6][7][8][9][10][17][18][19] Association Between Narcolepsy and Schizophrenia-Like Psychosis Psychosis in Patients with Narcolepsy Narcolepsy has been most commonly associated with depression, reported in some series at prevalence rates up to 25%, 20-23 although other data suggest the rate is no higher than in the general population. 6,24 Additionally, treatments such as modafinil and methylphenidate have been used successfully as first-line or augmenting agents in depression, [25][26][27] while antidepressant medications are used for their anticataplectic effects.…”

“…In a number of series, psychosis in narcolepsy has been attributed to stimulants at rates ranging from 30% to 100%. 6,32,33 Paradoxically, cases of treatment-refractory schizophrenia have been reported in which both psychotic and narcoleptic symptoms responded to treatment with stimulant medication, 8,9,[34][35][36] although hallucinations only partially. 7,37 Neuroleptics worsen narcoleptic somnolence, 7,37 as dopamine outflow is central to cortical wakefulness.…”

“…2,3 Most cases are sporadic, although genetic factors play a complex role, with first-degree relatives having a 40-fold increased risk; monozygotic twins, however, have only 25% concordance rates. 4 Psychosis has long been associated with narcolepsy, 5 although authors have differed on whether psychosis presenting with narcolepsy represents co-incidence, 6 a core ''psychotic form'' of narcolepsy, [7][8][9] or a result of stimulant treatment. 6,10 The reduced dopaminergic tone observed in narcolepsy would suggest an inverse relationship between narcolepsy and psychotic illnesses, the latter being widely considered to result from increased dopaminergic transmission.…”