Wu Sally, Panganiban Kristoffer J, Lee Jiwon, Li Dan, Smith Emily C C, Maksyutynska Kateryna, Humber Bailey, Ahmed Tariq, Agarwal Sri Mahavir, Ward Kristen, Hahn Margaret
Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, ON M6J 1H3, Canada.
Institute of Medical Sciences, University of Toronto, Toronto, ON M5T 1R8, Canada.
Metabolites. 2024 Aug 28;14(9):475. doi: 10.3390/metabo14090475.
Metabolic dysfunction is commonly observed in schizophrenia spectrum disorders (SSDs). The causes of metabolic comorbidity in SSDs are complex and include intrinsic or biological factors linked to the disorder, which are compounded by antipsychotic (AP) medications. The exact mechanisms underlying SSD pathophysiology and AP-induced metabolic dysfunction are unknown, but dysregulated lipid metabolism may play a role. Lipidomics, which detects lipid metabolites in a biological sample, represents an analytical tool to examine lipid metabolism. This systematic review aims to determine peripheral lipid signatures that are dysregulated among individuals with SSDs (1) with minimal exposure to APs and (2) during AP treatment. To accomplish this goal, we searched MEDLINE, Embase, and PsychINFO databases in February 2024 to identify all full-text articles written in English where the authors conducted lipidomics in SSDs. Lipid signatures reported to significantly differ in SSDs compared to controls or in relation to AP treatment and the direction of dysregulation were extracted as outcomes. We identified 46 studies that met our inclusion criteria. Most of the lipid metabolites that significantly differed in minimally AP-treated patients vs. controls comprised glycerophospholipids, which were mostly downregulated. In the AP-treated group vs. controls, the significantly different metabolites were primarily fatty acyls, which were dysregulated in conflicting directions between studies. In the pre-to-post AP-treated patients, the most impacted metabolites were glycerophospholipids and fatty acyls, which were found to be primarily upregulated and conflicting, respectively. These lipid metabolites may contribute to SSD pathophysiology and metabolic dysfunction through various mechanisms, including the modulation of inflammation, cellular membrane permeability, and metabolic signaling pathways.
代谢功能障碍在精神分裂症谱系障碍（SSDs）中很常见。SSDs中代谢合并症的病因复杂，包括与该疾病相关的内在或生物学因素，抗精神病药物（AP）会使这些因素更加复杂。SSDs病理生理学和AP诱导的代谢功能障碍的具体机制尚不清楚，但脂质代谢失调可能起了作用。脂质组学可检测生物样本中的脂质代谢物，是一种用于研究脂质代谢的分析工具。本系统综述旨在确定在（1）极少接触AP的SSDs个体和（2）AP治疗期间脂质代谢失调的外周脂质特征。为实现这一目标，我们于2024年2月检索了MEDLINE、Embase和PsychINFO数据库，以识别所有用英文撰写的全文文章，其中作者对SSDs进行了脂质组学研究。提取报告显示与对照组相比在SSDs中显著不同或与AP治疗及失调方向相关的脂质特征作为研究结果。我们确定了46项符合纳入标准的研究。在极少接受AP治疗的患者与对照组相比，显著不同的大多数脂质代谢物包括甘油磷脂，其大多下调。在接受AP治疗的组与对照组相比，显著不同的代谢物主要是脂肪酰基，其在不同研究中的失调方向相互矛盾。在接受AP治疗前后的患者中，受影响最大的代谢物是甘油磷脂和脂肪酰基，分别发现主要上调且相互矛盾。这些脂质代谢物可能通过多种机制导致SSDs病理生理学和代谢功能障碍，包括调节炎症、细胞膜通透性和代谢信号通路。
