Zhao Lei, Liu Hua, Wang Wenjuan, Wang Youping, Xiu Meihong, Li Shuyun
Qingdao Mental Health Center, Qingdao, Shandong, China.
Department of Nutritional and Metabolic Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China.
Front Pharmacol. 2023 Aug 17;14:1255501. doi: 10.3389/fphar.2023.1255501. eCollection 2023.
Cognitive impairment is one of the core symptoms of schizophrenia, which is stable and lifelong. L-carnitine has been shown to improve cognitive function and decrease the rate of cognitive deterioration in patients with Alzheimer's disease. However, it remains unclear regarding the role of L-carnitine and its metabolites in cognitive functions in schizophrenia after treatment with olanzapine. The purpose of this study was to evaluate the relationship between changes in plasma levels of L-carnitine metabolites and cognitive improvement after olanzapine treatment. This was a prospective longitudinal study. In this study, we recruited 25 female patients with first episode schizophrenia (FES) who were drug naïve at baseline and received 4 weeks of olanzapine monotherapy. Cognitive function was assessed at baseline and 4-week follow-up using the RBANS. Plasma L-carnitine metabolite levels were determined by a metabolomics technology based on untargeted ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). We found that the immediate memory index, delayed memory index and RBANS composite score were significantly increased at the 4-week follow-up after treatment. A total of 7 differential L-carnitine metabolites were identified in FES patients after olanzapine monotherapy. In addition, we found that changes in butyrylcarnitine were positively correlated with improvements in language index and RBANS composite score. Further regression analyses confirmed the association between reduced butyrylcarnitine levels and cognitive improvement after olanzapine monotherapy in FES patients. Our study shows that cognitive improvement after olanzapine treatment was associated with changes in L-carnitine metabolite levels in patients with FES, suggesting a key role of L-carnitine in cognition in schizophrenia.
认知障碍是精神分裂症的核心症状之一，具有稳定性且伴随终生。左旋肉碱已被证明可改善阿尔茨海默病患者的认知功能并降低认知衰退率。然而，奥氮平治疗后左旋肉碱及其代谢产物在精神分裂症认知功能中的作用仍不清楚。本研究的目的是评估奥氮平治疗后血浆左旋肉碱代谢产物水平变化与认知改善之间的关系。这是一项前瞻性纵向研究。在本研究中，我们招募了25例首发精神分裂症（FES）女性患者，她们在基线时未服用过药物，接受了4周的奥氮平单药治疗。在基线和4周随访时使用RBANS评估认知功能。血浆左旋肉碱代谢产物水平通过基于非靶向超高效液相色谱-质谱联用（UPLC-MS）的代谢组学技术测定。我们发现治疗后4周随访时即刻记忆指数、延迟记忆指数和RBANS综合评分显著增加。奥氮平单药治疗后，FES患者共鉴定出7种差异左旋肉碱代谢产物。此外，我们发现丁酰肉碱的变化与语言指数和RBANS综合评分的改善呈正相关。进一步的回归分析证实了FES患者奥氮平单药治疗后丁酰肉碱水平降低与认知改善之间的关联。我们的研究表明，奥氮平治疗后的认知改善与FES患者左旋肉碱代谢产物水平的变化有关，提示左旋肉碱在精神分裂症认知中起关键作用。
