Yuksel Cagri, Chen Xi, Chouinard Virginie-Anne, Nickerson Lisa D, Gardner Margaret, Cohen Talia, Öngür Dost, Du Fei
McLean Hospital, Belmont, MA.
Harvard Medical School, Boston, MA.
Schizophr Bull Open. 2021 Jan 30;2(1):sgaa073. doi: 10.1093/schizbullopen/sgaa073. eCollection 2021 Jan.
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 phosphorus magnetization transfer spectroscopy, we measured CK first-order forward rate constant ( ) in the frontal lobe, in patients with first-episode psychosis (FEP; = 16) and healthy controls ( = 34), at rest.
CK 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 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.
越来越多的证据表明精神分裂症和其他精神障碍存在脑能量代谢受损。肌酸激酶（CK）在细胞内提供三磷酸腺苷并在能量需求增加时维持其水平方面起着关键作用。然而，尚未对首发精神分裂症谱系障碍患者的CK活性进行研究。
利用磷磁化转移光谱技术，我们在静息状态下测量了首发精神病（FEP；n = 16）患者和健康对照者（n = 34）额叶的CK一级正向速率常数（ ）。
与健康对照者相比，FEP患者的CK 显著降低。两组之间在其他能量代谢相关指标上没有差异，包括磷酸肌酸（PCr）或三磷酸腺苷（ATP）。我们还发现患者体内甘油-3-磷酸胆碱（一种假定的膜分解产物）增加。
本研究结果表明，脑生物能异常在精神分裂症谱系障碍病程早期就已存在。需要进一步研究以确定CK 降低与精神症状之间的关系，并测试针对该途径的治疗方案。甘油-3-磷酸胆碱增加与未用药患者的早期研究以及首发精神分裂症的后期研究结果一致，并提示突触修剪增强。
