Meng Fanhao, Wang Jing, Wang Long, Zou Wei
The Graduate School, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang 150040, China.
First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang 150040, China.
Brain Res Bull. 2025 Feb;221:111191. doi: 10.1016/j.brainresbull.2025.111191. Epub 2025 Jan 7.
Major depressive disorder (MDD) is a common mental disorder with chronic tendencies that seriously affect regular work, life, and study. However, its exact pathogenesis remains unclear. Patients with MDD experience systemic and localized impairments in glucose metabolism throughout the disease course, disrupting various processes such as glucose uptake, glycoprotein transport, glycolysis, the tricarboxylic acid cycle (TCA), and oxidative phosphorylation (OXPHOS). These impairments may result from mechanisms including insulin resistance, hyperglycemia-induced damage, oxidative stress, astrocyte abnormalities, and mitochondrial dysfunction, leading to insufficient energy supply, altered synaptic plasticity, neuronal cell death, and functional and structural damage to reward networks. These mechanical changes contribute to the pathogenesis of MDD and severely interfere with the prognosis. Herein, we summarized the impairment of glucose metabolism and its pathophysiological mechanisms in patients with MDD. In addition, we briefly discussed potential pharmacological interventions for glucose metabolism to alleviate MDD, including glucagon-like peptide-1 receptor agonists, metformin, topical insulin, liraglutide, and pioglitazone, to encourage the development of new therapeutics.
重度抑郁症（MDD）是一种常见的慢性精神障碍，严重影响正常的工作、生活和学习。然而，其确切发病机制尚不清楚。MDD患者在整个病程中会出现全身和局部葡萄糖代谢受损，扰乱葡萄糖摄取、糖蛋白转运、糖酵解、三羧酸循环（TCA）和氧化磷酸化（OXPHOS）等各种过程。这些损伤可能源于胰岛素抵抗、高血糖诱导的损伤、氧化应激、星形胶质细胞异常和线粒体功能障碍等机制，导致能量供应不足、突触可塑性改变、神经元细胞死亡以及奖赏网络的功能和结构损伤。这些机制变化促成了MDD的发病机制，并严重干扰预后。在此，我们总结了MDD患者葡萄糖代谢的损伤及其病理生理机制。此外，我们简要讨论了针对葡萄糖代谢以缓解MDD的潜在药物干预措施，包括胰高血糖素样肽-1受体激动剂、二甲双胍、外用胰岛素、利拉鲁肽和吡格列酮，以促进新疗法的开发。
