McLean Hospital, Belmont, MA, USA.
Harvard Medical School, Boston, MA, USA.
Mol Psychiatry. 2015 Sep;20(9):1079-84. doi: 10.1038/mp.2015.13. Epub 2015 Mar 10.
Converging evidence suggests bioenergetic abnormalities in bipolar disorder (BD). In the brain, phosphocreatine (PCr) acts a reservoir of high-energy phosphate (HEP) bonds, and creatine kinases (CK) catalyze the transfer of HEP from adenosine triphosphate (ATP) to PCr and from PCr back to ATP, at times of increased need. This study examined the activity of this mechanism in BD by measuring the levels of HEP molecules during a stimulus paradigm that increased local energy demand. Twenty-three patients diagnosed with BD-I and 22 healthy controls (HC) were included. Levels of phosphorus metabolites were measured at baseline and during visual stimulation in the occipital lobe using (31)P magnetic resonance spectroscopy at 4T. Changes in metabolite levels showed different patterns between the groups. During stimulation, HC had significant reductions in PCr but not in ATP, as expected. In contrast, BD patients had significant reductions in ATP but not in PCr. In addition, PCr/ATP ratio was lower at baseline in patients, and there was a higher change in this measure during stimulation. This pattern suggests a disease-related failure to replenish ATP from PCr through CK enzyme catalysis during tissue activation. Further studies measuring the CK flux in BD are required to confirm and extend this finding.
越来越多的证据表明双相情感障碍 (BD) 存在生物能量异常。在大脑中，磷酸肌酸 (PCr) 充当高能磷酸盐 (HEP) 键的储库，肌酸激酶 (CK) 催化 HEP 从三磷酸腺苷 (ATP) 转移到 PCr 并从 PCr 转移回 ATP，在需要增加时进行。本研究通过测量在增加局部能量需求的刺激范式期间 HEP 分子的水平来检查该机制在 BD 中的活性。纳入了 23 名被诊断为 BD-I 的患者和 22 名健康对照者 (HC)。使用 4T 的 (31)P 磁共振波谱在枕叶测量基线和视觉刺激期间磷代谢物的水平。代谢物水平的变化在两组之间呈现出不同的模式。在刺激期间，HC 的 PCr 显著减少，但 ATP 没有减少，这是预期的。相比之下，BD 患者的 ATP 显著减少，但 PCr 没有减少。此外，患者的基线时 PCr/ATP 比值较低，在刺激期间该指标的变化更大。这种模式表明，在组织激活过程中，CK 酶催化从 PCr 补充 ATP 的能力出现与疾病相关的失败。需要进一步研究测量 BD 中的 CK 通量以证实并扩展这一发现。
