Psychotic Disorders Division, McLean Hospital, Belmont, MA, 02478, USA.
McLean Imaging Center, McLean Hospital, Belmont, MA, 02478, USA.
Mol Psychiatry. 2021 Jun;26(6):2483-2492. doi: 10.1038/s41380-020-00993-z. Epub 2021 Jan 4.
Psychotic Disorders such as schizophrenia (SZ) and bipolar disorder (BD) are characterized by abnormal functional connectivity (FC) within neural networks such as the default mode network (DMN), as well as attenuated anticorrelation between DMN and task-positive networks (TPN). Bioenergetic processes are critical for synaptic connectivity and are also abnormal in psychotic disorders. We therefore examined the association between brain energy metabolism and FC in psychotic disorders. P magnetization transfer spectroscopy from medial prefrontal cortex (MPFC) and whole-brain fMRI data were collected from demographically matched groups of SZ, BD, and healthy control (HC) subjects. The creatine kinase (CK) reaction flux calculated from spectroscopy was used as an index of regional energy production rate. FC maps were generated with MPFC as the seed region. Compared to HC, SZ showed significantly lower CK flux, while both BD and SZ patients showed decreased anticorrelation between MPFC and TPN. CK flux was significantly correlated with FC between MPFC and other DMN nodes in HC. This positive correlation was reduced modestly in BD and strongly in SZ. CK flux was negatively correlated with the anticorrelation between MPFC and TPN in HC, but this relationship was not observed in BD or SZ. These results indicate that MPFC energy metabolism rates are associated with stronger FC within networks and stronger anticorrelation between networks in HC. However, this association is decreased in SZ and BD, where bioenergetic and FC abnormalities are evident. This pattern may suggest that impairment in energy production in psychotic disorders underlies the impaired neural connectivity.
精神障碍，如精神分裂症（SZ）和双相情感障碍（BD）的特点是神经网络（如默认模式网络（DMN））中的异常功能连接（FC），以及 DMN 与任务正性网络（TPN）之间的相关性减弱。生物能量过程对于突触连接至关重要，在精神障碍中也是异常的。因此，我们研究了精神障碍中脑能量代谢与 FC 之间的关系。从内侧前额叶皮层（MPFC）采集 P 磁化转移光谱和全脑 fMRI 数据，这些数据来自人口统计学匹配的 SZ、BD 和健康对照组（HC）受试者。从光谱计算的肌酸激酶（CK）反应通量被用作区域能量产生率的指标。以 MPFC 为种子区域生成 FC 图。与 HC 相比，SZ 患者的 CK 通量明显降低，而 BD 和 SZ 患者的 MPFC 与 TPN 之间的相关性降低。在 HC 中，CK 通量与 MPFC 与其他 DMN 节点之间的 FC 呈显著正相关。在 BD 中，这种正相关略有降低，而在 SZ 中则显著降低。CK 通量与 HC 中 MPFC 与 TPN 之间的负相关相关，但在 BD 或 SZ 中未观察到这种关系。这些结果表明，MPFC 能量代谢率与 HC 中网络内的更强 FC 以及网络之间的更强相关性相关。然而，在 SZ 和 BD 中，这种关联减少了，在这些疾病中，生物能量和 FC 异常是明显的。这种模式可能表明，精神障碍中的能量产生受损是神经连接受损的基础。
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