Orexin-a elevation in antipsychotic-treated compared to drug-free patients with schizophrenia: A medication effect independent of metabolic syndrome

TY - JOUR

T1 - Orexin-a elevation in antipsychotic-treated compared to drug-free patients with schizophrenia

T2 - A medication effect independent of metabolic syndrome

AU - Chen, Po Yu

AU - Chang, Chin Kuo

AU - Chen, Chun Hsin

AU - Fang, Su Chen

AU - Mondelli, Valeria

AU - Chiu, Chih Chiang

AU - Lu, Mong Liang

AU - Hwang, Ling Ling

AU - Huang, Ming Chyi

N1 - Funding Information: This work was supported by the Ministry of Science and Technology , Taiwan ( 109-2314-B-532-005 , 110-2314-B-532-004 , and 110-2314-B-532-005-MY3 ); Taipei City Government , ( 11001-62-003 , 11001-62-017 , 11101-62-031 , and 11101-62-029 ), Taipei City Hospital ( TPCH-110-51 , 110-63 , 111-56 , and 111-57 ), and Taipei Institute of Pathology ( TIP-109-001 and 110-003 ), Taipei, Taiwan. Publisher Copyright: © 2022

PY - 2022/11

Y1 - 2022/11

N2 - Background/Purpose: Orexin-A levels are reportedly increased in antipsychotic (APD)-treated patients with schizophrenia compared to healthy controls and have been associated with metabolic abnormalities. It is not clear whether the orexin-A elevation is related specifically to the drug (APDs) effect, which should be clarified by including a drug-free group for comparison, or related to drug-induced metabolic abnormalities. Methods: Blood orexin-A levels and metabolic profiles were compared between 37 drug-free, 45 aripiprazole-treated, and 156 clozapine-treated patients with schizophrenia. The association between orexin-A and metabolic outcomes were examined. We explored the effects of APDs treatment and metabolic status on orexin-A levels by linear regression. Results: Patients under APDs treatment had increased orexin-A levels compared to drug-free patients, with aripiprazole-treated group having higher orexin-A levels than clozapine-treated group. Higher orexin-A levels reduced the risks of metabolic syndrome (MS) and type 2 diabetes mellitus, indicating a relationship between orexin-A levels and metabolic problems. After adjusting the effect from metabolic problems, we found APD treatment is still associated with orexin-A regulation, with aripiprazole more significantly than clozapine. Conclusion: With the inclusion of drug-free patients rather than healthy controls for comparison, we demonstrated that orexin-A is upregulated following APD treatment even after we controlled the potential effect from MS, suggesting an independent effect of APDs on orexin-A levels. Furthermore, the effect differed between APDs with dissimilar obesogenicity, i.e. less obesogenicity likely associated with higher orexin-A levels. Future prospective studies exploring the causal relationship between APDs treatment and orexin-A elevation as well as the underlying mechanisms are warranted.

AB - Background/Purpose: Orexin-A levels are reportedly increased in antipsychotic (APD)-treated patients with schizophrenia compared to healthy controls and have been associated with metabolic abnormalities. It is not clear whether the orexin-A elevation is related specifically to the drug (APDs) effect, which should be clarified by including a drug-free group for comparison, or related to drug-induced metabolic abnormalities. Methods: Blood orexin-A levels and metabolic profiles were compared between 37 drug-free, 45 aripiprazole-treated, and 156 clozapine-treated patients with schizophrenia. The association between orexin-A and metabolic outcomes were examined. We explored the effects of APDs treatment and metabolic status on orexin-A levels by linear regression. Results: Patients under APDs treatment had increased orexin-A levels compared to drug-free patients, with aripiprazole-treated group having higher orexin-A levels than clozapine-treated group. Higher orexin-A levels reduced the risks of metabolic syndrome (MS) and type 2 diabetes mellitus, indicating a relationship between orexin-A levels and metabolic problems. After adjusting the effect from metabolic problems, we found APD treatment is still associated with orexin-A regulation, with aripiprazole more significantly than clozapine. Conclusion: With the inclusion of drug-free patients rather than healthy controls for comparison, we demonstrated that orexin-A is upregulated following APD treatment even after we controlled the potential effect from MS, suggesting an independent effect of APDs on orexin-A levels. Furthermore, the effect differed between APDs with dissimilar obesogenicity, i.e. less obesogenicity likely associated with higher orexin-A levels. Future prospective studies exploring the causal relationship between APDs treatment and orexin-A elevation as well as the underlying mechanisms are warranted.

KW - Antipsychotics

KW - Metabolic syndrome

KW - Orexin-A

KW - Schizophrenia

KW - Type 2 diabetes mellitus

UR - http://www.scopus.com/inward/record.url?scp=85127715782&partnerID=8YFLogxK

U2 - 10.1016/j.jfma.2022.03.008

DO - 10.1016/j.jfma.2022.03.008

M3 - Article

AN - SCOPUS:85127715782

SN - 0929-6646

VL - 121

SP - 2172

EP - 2181

JO - Journal of the Formosan Medical Association

JF - Journal of the Formosan Medical Association

IS - 11

ER -