Abnormal Brain Bioenergetics in First-Episode Psychosis.
Abnormal Brain Bioenergetics in First-Episode Psychosis.
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DOI：
10.1093/schizbullopen/sgaa073
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发表时间：
2021-01
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影响因子：
--
通讯作者：
Du F
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文献类型：
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作者：
Yuksel C;Chen X;Chouinard VA;Nickerson LD;Gardner M;Cohen T;Öngür D;Du F
越来越多的证据表明，精神分裂症和其他精神疾病的大脑能量代谢受损。肌酸激酶（CK）在细胞中提供三磷酸腺苷并在能量需求增加时维持其水平方面至关重要。然而，CK的活性尚未在首发精神分裂症谱系障碍患者中进行研究。 使用体内磷磁化传递光谱，我们测量了CK一阶正向速率常数（kf）在额叶，在首发精神病患者（FEP; n = 16）和健康对照组（n = 34），在休息。 与健康对照组相比，FEP组CK kf显著降低。两组间其他能量代谢相关指标（包括磷酸肌酸（PCr）或ATP）无差异。我们还发现增加甘油-3-磷酸胆碱，一个假定的膜分解产物，在患者。 这项研究的结果表明，大脑生物能量异常已经存在于精神分裂症谱系障碍的早期过程中。未来的研究是必要的，以确定减少CK kf与精神病症状的关系，并测试针对这一途径的治疗方案。甘油-3-磷酸胆碱的增加与早期在药物初治患者中的研究和后来在首发精神分裂症中的研究一致，并表明突触修剪增强。
Converging evidence indicates impaired brain energy metabolism in schizophrenia and other psychotic disorders. Creatine kinase (CK) is pivotal in providing adenosine triphosphate in the cell and maintaining its levels when energy demand is increased. However, the activity of CK has not been investigated in patients with first-episode schizophrenia spectrum disorders. Using in vivo phosphorus magnetization transfer spectroscopy, we measured CK first-order forward rate constant (kf) in the frontal lobe, in patients with first-episode psychosis (FEP; n = 16) and healthy controls (n = 34), at rest. CK kf was significantly reduced in FEP compared to healthy controls. There were no differences in other energy metabolism-related measures, including phosphocreatine (PCr) or ATP, between groups. We also found increase in glycerol-3-phosphorylcholine, a putative membrane breakdown product, in patients. The results of this study indicate that brain bioenergetic abnormalities are already present early in the course of schizophrenia spectrum disorders. Future research is needed to identify the relationship of reduced CK kf with psychotic symptoms and to test treatment alternatives targeting this pathway. Increased glycerol-3-phosphorylcholine is consistent with earlier studies in medication-naïve patients and later studies in first-episode schizophrenia, and suggest enhanced synaptic pruning.