Hostname: page-component-7479d7b7d-qlrfm Total loading time: 0 Render date: 2024-07-12T19:30:26.408Z Has data issue: false hasContentIssue false
  • English
  • Français

Narcolepsy: Differential Diagnosis or Etiology in Some Cases of Bipolar Disorder and Schizophrenia?

Published online by Cambridge University Press:  07 November 2014

Alan B. Douglass
Get access Rights & Permissions [Opens in a new window]

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 DQB10602 (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.

Type
Review
Information
CNS Spectrums , Volume 8 , Issue 2: Sleep Disorders , February 2003 , pp. 120 - 126
Copyright
Copyright © Cambridge University Press 2003

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

1.Gelineau, J. De la narcolepsie. Gaz Hop (Paris). 1880;53:626.Google Scholar
2.Daniels, L. Narcolepsy. Medicine. 1934;13:1.CrossRefGoogle Scholar
3.Yoss, R, Daly, D. Criteria for the diagnosis of the narcoleptic syndrome. Proc Staff Meet Mayo Clin. 1957;32:320.Google ScholarPubMed
4.Bladin, PF. Narcolepsy–cataplexy and psychoanalytic theory of sleep and dreams. J Hist Neurosci. 2000;9:203–217.CrossRefGoogle ScholarPubMed
5.Guilleminault, C, Dement, W, Passouant, P, eds. Narcolepsy. New York, NY: Spectrum Publications, Inc.; 1976.Google ScholarPubMed
6.Thorpy, M, Committee DCS. International classification of sleep disorders: Diagnostic and Coding Manual. Rochester, MN: Association of Sleep Disorders Centers; 1990Google Scholar
7.Coren, H, Strain, J. A case of narcolepsy with psychosis (paranoid state of narcolepsy). Compr Psychiatry. 1965;6:191.CrossRefGoogle ScholarPubMed
8.Amira, SA, Johnson, TS, Logowitz, NB. Diagnosis of narcolepsy using the multiple sleep latency test: analysis of current laboratory criteria. Sleep. 1985;8:325–331.CrossRefGoogle ScholarPubMed
9.Carskadon, MA, Dement, WC, Mitler, MM, Roth, T, Westbrook, PR, Keenan, S. Guidelines for the multiple sleep latency test (MSLT): a standard measure of sleepiness. Sleep. 1986;9:519–524.CrossRefGoogle ScholarPubMed
10.Billiard, M, Seignalet, J, Besset, A, Cadilhac, J. HLA-DR2 and narcolepsy. Sleep, 1986;9(pt 2):149–152.CrossRefGoogle ScholarPubMed
11.Honda, Y, Juji, T, Matsuki, K, et al.HLA-DR2 and Dw2 in narcolepsy and in other disorders of excessive somnolence without cataplexy. Sleep. 1986;9(pt 2):133–142.CrossRefGoogle ScholarPubMed
12.Juji, T, Satake, M, Honda, Y, Doi, Y. HLA antigens in Japanese patients with narcolepsy. All the patients were DR2 positive. Tissue Antigens. 1984;24:316–319.CrossRefGoogle Scholar
13.Olerup, O, Schaffer, M, Hillert, J, Sachs, C. The narcolepsy-associated DRw15, DQw6, Dw2 haplotype has no unique HLA-DQA or -DQB restriction fragments and does not extend to the HLA-DP subregion. Immunogenetics. 1990;32:41–44.CrossRefGoogle ScholarPubMed
14.Mignot, E, Lin, L, Rogers, W, et al.Complex HLA-DR and -DQ interactions confer risk of narcolepsy-cataplexy in three ethnic groups. Am J Hum Genet. 2000; 68:686–699.CrossRefGoogle Scholar
15.Mignot, E. Genetic and familial aspects of narcolepsy. Neurology. 1998;50(suppl 1):16–22.CrossRefGoogle ScholarPubMed
16.Lin, L, Hungs, M, Mignot, E. Narcolepsy and the HLA region. J Neuroimmunol. 2001;117(1–2):9–20.CrossRefGoogle ScholarPubMed
17.Lin, L, Faraco, J, Li, R, et al.The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Cell. 1999;98:365–376.CrossRefGoogle ScholarPubMed
18.Chemelli, RM, Willie, JT, Sinton, CM, et al.Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell. 1999;98:437–451.CrossRefGoogle ScholarPubMed
19.Nishino, S, Ripley, B, Overeem, S, Lammers, GJ, Mignot, E. Hypocretin (orexin) deficiency in human narcolepsy. Lancet. 2000;355:39–40.CrossRefGoogle ScholarPubMed
20.Peyron, C, Faraco, J, Rogers, W, et al.A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. Nat Med. 2000;6;991–997.CrossRefGoogle Scholar
21.Thannickal, TC, Moore, TY, Nienhuis, R, et al.Reduced number of hypocretin neurons in human narcolepsy. Neuron. 2000;27:469–744.CrossRefGoogle ScholarPubMed
22.Sakurai, T, Amemiya, A, Ishii, M, et al.Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell. 1998;92:573–585.CrossRefGoogle Scholar
23.Siegel, JM, Moore, R, Thannickal, T, Nienhuis, R. A brief history of hypocretin/orexin and narcolepsy. Neuropsychopharmacology. 2001;25(suppl 5):14–20.CrossRefGoogle ScholarPubMed
24.Peyron, C, Tighe, DK, van den Pol, AN, et al.Neurons containing Hypocretin (orexin) project to multiple neuronal systems. J Neurosci. 1998 18:9996–10015.CrossRefGoogle ScholarPubMed
25.Marcus, JN, Aschkenasi, CJ, Lee, CE, et al.Differential expression of orexin receptors 1 and 2 in the rat brain. J Comp Neurol. 2001; 435:6–25.CrossRefGoogle ScholarPubMed
26.Mignot, E. A commentary on the neurobiology of the hypocretin/orexin system. Neuropsychopharmacology. 2001;25(suppl 5):5–13.CrossRefGoogle ScholarPubMed
27.Yoshida, Y, Fujiki, N, Nakajima, T, et al.Fluctuation of extracellular hypocretin-1 (orexin-A) levels in the rat in relation to the light-dark cycle and sleep-wake activities. Eur J Neurosci. 2001;14:1075–81.CrossRefGoogle Scholar
28.Mignot, E, Lammers, G, Ripley, B, et al.The role of CSF Hypocretin measurements in the diagnosis of narcolepsy and other hypersomnias. Arch Neurol. In press.Google Scholar
29.Wisor, JP, Nishino, S, Sora, I, et al.Dopaminergic role in stimulant–induced wakefulness. J Neurosci.. 2001;21:1787–1794.CrossRefGoogle ScholarPubMed
30.Smith, CM. Psychosomatic aspects of narcolepsy. J Mental Science. 1958;104:593–607.CrossRefGoogle ScholarPubMed
31.Shapiro, B, Spitz, H. Problems in the differential diagnosis of narcolepsy versus schizophrenia. Am J Psychiatry. 1976;133:1321–1323.Google ScholarPubMed
32.Ullman, KC. Narcolepsy and schizophrenia [letter]. Am J Psychiatry. 1977;134:822.Google ScholarPubMed
33.Rockwell, DA. Differentiating narcolepsy [letter]. Am J Psychiatry. 1978;135:387.CrossRefGoogle ScholarPubMed
34.Schrader, G, Hicks, EP. Narcolepsy, paranoid psychosis, major depression, and tardive dyskinesia. J Nerv Ment Dis. 1984;172:439–441.CrossRefGoogle ScholarPubMed
35.Douglass, AB, Hays, P, Pazderka, F, Russell, JM. Florid refractory schizophrenias that turn out to be treatable variants of HLA-associated narcolepsy. J Nerv Ment Dis. 1991;179:12–17.CrossRefGoogle ScholarPubMed
36.Douglass, AB, Shipley, JE, Haines, RF, et al.Schizophrenia, narcolepsy, and HLA-DR15, DQ6. Biol Psychiatry. 1993;34:773–780.CrossRefGoogle ScholarPubMed
37.Silvestri, R, Montagnese, C, de Domenico, P, et al.Narcolepsy and psychopathology: a case report. Acta Neurol. 1991;13:275–278.Google ScholarPubMed
38.Royant-Parola, S. [Narcolepsy and the psychiatric tableau. A specific form of narcolepsy?] Ann Med Psychol (Paris). 1992;150:286–290. French.Google Scholar
39.Takeuchi, N, Mukai, M, Uchimura, N, et al.A narcoleptic patient exhibiting hallucinations and delusion. Psychiatry Clin Neurosci. 2000;54:321–322.CrossRefGoogle ScholarPubMed
40.Jackson, C, Bachman, D. Narcolepsy-related psychosis misinterpreted as schizophrenia. Neuropsychiatry Neuropsychol Behav Neurol. 1996;9:139–140.Google Scholar
41.Dahl, RE, Holttum, J, Trubnick, L. A clinical picture of child and adolescent narcolepsy. J Am Acad Child Adolesc Psychiatry. 1994;33:834–841.CrossRefGoogle ScholarPubMed
42.Pawluk, L, Hurwitz, T, Schluter, J, et al.Psychiatric morbidity in narcoleptics on chronic high dose methylphenidate therapy. J Nerv Ment Dis. 1995;183:45–48.CrossRefGoogle ScholarPubMed
43.Meats, P, Hellewell, J, Jolley, D. Interaction between narcolepsy-cataplexy and bipolar mood disorder in an elderly woman. Int J Geriatr Psychiatry. 1992;7:135–137.CrossRefGoogle Scholar
44.Nofzinger, EA, Thase, ME, Reynolds, CF, Himmelhoch, JM. Hypersomnia in bipolar depression: a comparison with narcolepsy using the multiple sleep latency test. Am J Psychiatry. 1991;148:1177–1181.Google ScholarPubMed
45.Chowdari, KV, Xu, K, Zhang, F, et al.Immune related genetic polymorphisms and schizophrenia among the Chinese. Hum Immunol. 2001;62:714–724.CrossRefGoogle ScholarPubMed
46.Jonsson, EG, Zhang, F, Nimgaonkar, VL, Rudert, WA, Sedvall, GC. Lack of association between schizophrenia and HLA DQB1 alleles in a Swedish sample. Schizophr Res. 1998;29:293–296.CrossRefGoogle Scholar
47.Gibson, S, Straub, RE, Walsh, D, Kendler, KS, Gill, M. Schizophrenia and HLA: No association with PCR-SSOP typed classical loci in a large Irish familial sample. Am J Med Genet. 1999;88:422–429.Google Scholar
48.Haider, MZ, Zahid, MA, Dalal, HN, Razik, MA. Human leukocyte antigen (HLA) DRB1 alleles in Kuwaiti Arabs with schizophrenia. Am J Med Genet. 2000;96:870–872.3.0.CO;2-L>CrossRefGoogle ScholarPubMed
49.Nimgaonkar, VL, Rudert, WA, Zhang, X, Trucco, M, Ganguli, R. Negative association of schizophrenia with HLA DQB1*0602: evidence from a second African-American cohort. Schizophr Res. 1997;23:81–86.CrossRefGoogle ScholarPubMed
50.Wright, P, Nimgaonkar, VL, Donaldson, PT, Murray, RM. Schizophrenia and HLA: a review. Schizophr Res. 2001;47:1–12.CrossRefGoogle ScholarPubMed
51.Hays, P. The nosological status of schizophrenia. Lancet. 1984;1:1342–1345.CrossRefGoogle ScholarPubMed
52.Wright, P, Donaldson, PT, Underhill, JA, et al.Genetic association of the HLA DRB1 gene locus on chromosome 6p21.3 with schizophrenia. Am J Psychiatry. 1996;153:1530–1533.Google ScholarPubMed
53.Aldrich, MS. The clinical spectrum of narcolepsy and idiopathic hypersomnia. Neurology. 1996;46:393–401.CrossRefGoogle ScholarPubMed
54.Hicks, JA, Shapiro, C. Pseudo-narcolepsy: case report. J Psychiatry Neurosci. 1999;24:348–350.Google ScholarPubMed
55.Howland, RH. Sleep-onset rapid eye movement periods in neuropsychiatric disorders: implications for the pathophysiology of psychosis. J New Ment Dis. 1997;185:730–738.CrossRefGoogle ScholarPubMed
56.Salomon, RM, Ripley, B, Kennedy, JS, et al.Diurnal variation of CSF hypocretin-1 levels in control and depressed subjects. Biol Psychiatry. In press.Google Scholar