Maddock Richard J, Smucny Jason
Department of Psychiatry and Behavioral Sciences, University of California, Davis, CA, USA.
Mol Psychiatry. 2025 Sep 5. doi: 10.1038/s41380-025-03206-7.
Anxiety disorders (AnxDs) are highly prevalent and often untreated or unresponsive to treatment. Although proton magnetic resonance spectroscopy (1H-MRS) studies of AnxDs have been conducted for over 25 years, a consensus regarding neurometabolic abnormalities in these conditions is lacking.
A systematic review and meta-analysis of 1H-MRS studies of AnxDs (social anxiety disorder, generalized anxiety disorder, and panic disorder) identified 25 published datasets meeting inclusion criteria. These compared neurometabolites between 370 patients and 342 controls, including n-acetlyaspartate (NAA), total creatine, total choline (tCho), myo-inositol, glutamate, glutamate+glutamine, GABA, and lactate.
Across AnxDs, tCho was significantly reduced in prefrontal cortex and across all cortical regions. Effect sizes for cortical tCho were significantly more negative in studies with better measurement quality, with Hedges' g = -0.64 and an 8% mean reduction. NAA was unchanged in prefrontal cortex but reduced across all cortical regions (after exclusions). These abnormalities did not differ between the three disorders. No other neurometabolites differed significantly.
Reduced choline-containing compounds in cortical regions is a consistent, transdiagnostic abnormality in AnxDs. Notably, arousal-related neuromodulators, including norepinephrine, alter membrane phospholipid homeostasis and methylation reactions, which influence brain tCho levels. This suggests that chronically elevated arousal in AnxDs may increase neurometabolic demand for choline compounds without a proportionate increase in brain uptake, leading to reduced tCho levels. Reduced cortical NAA suggests compromised neuronal function in AnxDs. Future studies may clarify the clinical significance of reduced cortical tCho and the possibility that appropriate choline supplementation could have therapeutic benefit in anxiety disorders.
焦虑症（AnxDs）非常普遍，且常常未得到治疗或对治疗无反应。尽管针对焦虑症的质子磁共振波谱（1H-MRS）研究已开展了25年以上，但对于这些病症中的神经代谢异常仍缺乏共识。
对焦虑症（社交焦虑症、广泛性焦虑症和惊恐障碍）的1H-MRS研究进行系统综述和荟萃分析，确定了25个符合纳入标准的已发表数据集。这些数据集比较了370例患者和342例对照之间的神经代谢物，包括N-乙酰天门冬氨酸（NAA）、总肌酸、总胆碱（tCho）、肌醇、谷氨酸、谷氨酸+谷氨酰胺、γ-氨基丁酸（GABA）和乳酸。
在所有焦虑症中，前额叶皮质和所有皮质区域的tCho均显著降低。在测量质量较好的研究中，皮质tCho的效应量显著更负，Hedges' g = -0.64，平均降低8%。前额叶皮质中的NAA没有变化，但在所有皮质区域（排除后）降低。这三种疾病之间的这些异常没有差异。没有其他神经代谢物有显著差异。
皮质区域含胆碱化合物减少是焦虑症中一种一致的、跨诊断的异常。值得注意的是，包括去甲肾上腺素在内的与唤醒相关的神经调节剂会改变膜磷脂稳态和甲基化反应，从而影响脑内tCho水平。这表明焦虑症中慢性升高的唤醒可能会增加对胆碱化合物的神经代谢需求，而脑摄取没有相应增加，导致tCho水平降低。皮质NAA降低表明焦虑症中神经元功能受损。未来的研究可能会阐明皮质tCho降低的临床意义以及适当补充胆碱可能对焦虑症有治疗益处的可能性。
