Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Schizophr Res. 2019 Jun;208:324-330. doi: 10.1016/j.schres.2019.01.031. Epub 2019 Feb 11.
Memory is robustly impaired in schizophrenia (SZ) and related to functional outcome. Memory dysfunction has been shown to be related to altered brain glucose metabolism and brain insulin resistance in animal models and human studies of Alzheimer's disease. In this study, differences in brain glucose using magnetic resonance spectroscopy (MRS) and blood Extracellular Vesicle (EV) biomarkers of neuronal insulin resistance (i.e. Akt and signaling effectors) between SZ and controls were investigated, as well as whether these measures were related to memory impairments. Neuronal insulin resistance biomarkers showed a trend for being lower in SZ compared to controls, and memory measures were lower in SZ compared to controls. Occipital cortex glucose was higher in SZ compared to controls indicating lower brain glucose utilization. Linear regression analyses revealed significant relationships between neuronal insulin resistance biomarkers, memory measures, and brain glucose. More specifically, p70S6K, an insulin signaling effector, was related to verbal learning and brain MRS glucose in the SZ group. For the first time, we show that memory impairments in SZ may be related to brain glucose and brain insulin resistance. These data suggest that brain insulin resistance may play a role in the pathophysiology of learning and memory dysfunction in SZ.
精神分裂症（SZ）患者的记忆明显受损，且与功能预后相关。动物模型和阿尔茨海默病的人类研究表明，记忆功能障碍与大脑葡萄糖代谢和大脑胰岛素抵抗有关。在这项研究中，研究了使用磁共振波谱（MRS）和血外泌体（EV）神经元胰岛素抵抗生物标志物（即 Akt 和信号效应物）测量的大脑葡萄糖差异，以及这些测量值与记忆障碍之间的关系。与对照组相比，SZ 组的神经元胰岛素抵抗生物标志物呈下降趋势，且记忆测量值也低于对照组。与对照组相比，SZ 患者的枕叶皮层葡萄糖水平更高，表明大脑葡萄糖利用率降低。线性回归分析显示神经元胰岛素抵抗生物标志物、记忆测量值和大脑葡萄糖之间存在显著关系。更具体地说，胰岛素信号效应物 p70S6K 与 SZ 组的言语学习和大脑 MRS 葡萄糖有关。我们首次表明，SZ 中的记忆障碍可能与大脑葡萄糖和大脑胰岛素抵抗有关。这些数据表明，大脑胰岛素抵抗可能在 SZ 中学习和记忆功能障碍的病理生理学中起作用。
