Orexin-A Levels in Relation to the Risk of Metabolic Syndrome in Patients with Schizophrenia Taking Antipsychotics

Po-Yu Chen, Chun-Hsin Chen, Chin-Kuo Chang, Chung-Feng Kao, Mong-Liang Lu, Shih-Ku Lin, Ming-Chyi Huang, Ling-Ling Hwang, Valeria Mondelli

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


Background: The role of orexin-A in regulating metabolic homeostasis has been recognized, but its association with antipsychotic-induced metabolic abnormalities remains unclear. We investigated the association between orexin-A levels and metabolic syndrome in patients with schizophrenia treated with clozapine or less obesogenic antipsychotics compared with nonpsychiatric controls. Methods: Plasma orexin-A levels and metabolic parameters were determined in 159 patients with schizophrenia: 109 taking clozapine; 50 taking aripiprazole, amisulpride, ziprasidone, or haloperidol; and 60 nonpsychiatric controls. Results: Orexin-A levels were significantly higher in the group taking less obesogenic antipsychotics, followed by the clozapine group and the controls (F=104.6, P<.01). Higher orexin-A levels were correlated with better metabolic profiles in the patient groups but not in the controls. Regression analyses revealed that the patients with higher orexin-A levels had significantly lower risk of metabolic syndrome (adjusted odds ratio [OR]=0.04, 95% CI: 0.01-0.38 for the 2nd tertile; OR=0.04, 95% CI: 0.01-0.36 for the 3rd tertile, compared with the first tertile), after adjustment for age, sex, smoking history, types of antipsychotics (clozapine vs less obesogenic antipsychotics), duration of antipsychotic treatment, and disease severity. Conclusions: Our results revealed that the orexin-A level was upregulated in patients with schizophrenia treated with antipsychotics, especially for the group taking less obesogenic antipsychotics. Furthermore, higher orexin-A levels were independently associated with better metabolic profiles. These observations suggest that an upregulation of orexin-A has a protective effect against the development of metabolic abnormalities in patients with schizophrenia receiving antipsychotic treatment.

Original languageEnglish
Pages (from-to)28-36
Number of pages9
JournalInternational Journal of Neuropsychopharmacology
Issue number1
Early online dateSep 11 2018
Publication statusPublished - Sep 11 2018


  • antipsychotics
  • clozapine
  • metabolic syndrome
  • orexin-A
  • schizophrenia

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)


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