与未用药的精神分裂症患者相比，抗精神病药物治疗的患者中食欲素-A 升高：一种代谢综合征无关的药物作用。

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

机构信息

Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Psychiatry, Taipei City Psychiatric Center, Taipei City Hospital, Taipei, Taiwan.

Global Health Program, College of Public Health, National Taiwan University, Taipei, Taiwan; Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.

出版信息

J Formos Med Assoc. 2022 Nov;121(11):2172-2181. doi: 10.1016/j.jfma.2022.03.008. Epub 2022 Apr 6.

DOI:10.1016/j.jfma.2022.03.008

PMID:35396156

Abstract

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.

摘要

背景/目的：据报道，与健康对照组相比，抗精神病药物（APD）治疗的精神分裂症患者的食欲素-A 水平升高，并与代谢异常有关。目前尚不清楚这种食欲素-A 的升高是否与药物（APD）的作用有关，而通过纳入一个无药物组进行比较，应该可以明确这一点，或者是否与药物引起的代谢异常有关。

方法

比较了 37 名未服用药物、45 名阿立哌唑治疗和 156 名氯氮平治疗的精神分裂症患者的血液食欲素-A 水平和代谢谱。研究了食欲素-A 与代谢结果之间的关系。我们通过线性回归来探讨 APD 治疗和代谢状态对食欲素-A 水平的影响。

结果

与未服用药物的患者相比，服用 APD 的患者食欲素-A 水平升高，其中阿立哌唑治疗组的食欲素-A 水平高于氯氮平治疗组。较高的食欲素-A 水平降低了代谢综合征（MS）和 2 型糖尿病的风险，表明食欲素-A 水平与代谢问题之间存在关联。在调整了代谢问题的影响后，我们发现 APD 治疗仍与食欲素-A 的调节有关，阿立哌唑的作用比氯氮平更显著。

结论

通过纳入未服用药物的患者而不是健康对照组进行比较，我们证明了即使在控制了 MS 的潜在影响后，APD 治疗后食欲素-A 水平也会升高，这表明 APD 对食欲素-A 水平有独立的影响。此外，不同的 APD 对食欲素-A 水平的影响不同，即肥胖相关度较低的药物可能与较高的食欲素-A 水平相关。未来有必要进行前瞻性研究，探索 APD 治疗与食欲素-A 升高之间的因果关系以及潜在的机制。