Narcolepsy: differential diagnosis or etiology in some cases of bipolar disorder and schizophrenia?

Narcolepsy may be underdiagnosed in psychiatric patients because its hypnagogic hallucinations can be mistaken for schizophrenia or lead to a more severe bipolar diagnosis. The article reviews the clinical tetrad of narcolepsy—cataplexy, hypnagogic hallucinations, daytime sleep attacks, and sleep paralysis—and the role of orexin/hypocretin neuron loss, likely autoimmune. It argues that classical narcolepsy can now be ruled out in difficult psychiatric cases, and that psychotic patients with narcolepsy may need stimulants for recovery, as conventional antipsychotics could worsen symptoms.

Study at a glance

Abstract

Does narcolepsy, a neurological disease, need to be considered when diagnosing major mental illness? Clinicians have reported cases of narcolepsy with prominent hypnagogic hallucinations that were mistakenly diagnosed as schizophrenia. In some bipolar disorder patients with narcolepsy, the HH resulted in their receiving a more severe diagnosis (ie, bipolar disorder with psychotic features or schizoaffective disorder). The role of narcolepsy in psychiatric patients has remained obscure and problematic, and it may be more prevalent than commonly believed. Classical narcolepsy patients display the clinical "tetrad"--cataplexy, hypnagogic hallucinations, daytime sleep attacks, and sleep paralysis. Over 85% also display the human leukocyte antigen marker DQB1*0602 (subset of DQ6). Since 1998, discoveries in neuroanatomy and neurophysiology have greatly advanced the understanding of narcolepsy, which involves a nearly total loss of the recently discovered orexin/hypocretin (hypocretin) neurons of the hypothalamus, likely by an autoimmune mechanism. Hypocretin neurons normally supply excitatory signals to brainstem nuclei producing norepinephrine, serotonin, histamine, and dopamine, with resultant suppression of sleep. They also project to basal forebrain areas and cortex. A literature review regarding the differential diagnosis of narcolepsy, affective disorder, and schizophrenia is presented. Furthermore, it is now possible to rule out classical narcolepsy in difficult psychiatric cases. Surprisingly, psychotic patients with narcolepsy will likely require stimulants to fully recover. Many conventional antipsychotic drugs would worsen their symptoms and make them appear to become a "chronic psychotic," while in fact they can now be properly diagnosed and treated.