双相障碍中的能量代谢：从标志物到精准治疗。
完整摘要 · 中文译文
背景：双相障碍（BD）以反复发作的心境发作和功能损害为特征。越来越多的证据表明，线粒体功能障碍、氧化应激和代谢紊乱在其病理生理学中具有重要意义，影响神经元信号传导、突触可塑性和炎症通路。 目的：本综述综合当前将能量代谢与双相障碍联系起来的证据，整合神经影像学和外周生物标志物研究结果，并讨论针对线粒体和代谢功能障碍的新兴治疗策略。 方法：按照PRISMA指南，在PubMed、MEDLINE、EMBASE、Scopus和Cochrane Library中使用“双相障碍”、“能量代谢”和“线粒体”进行系统检索。纳入标准包括经同行评议的人类研究、原创研究和荟萃分析；排除儿童、非英文、饮食、遗传学或以共病为重点的研究。另外进行手工检索以查找特定生物标志物研究。 结果：证据一致显示双相障碍中存在氧化磷酸化受损、ATP和磷酸肌酸降低、NAD+/NADH比值改变以及氧化和炎症标志物升高。神经影像学显示PCr/ATP比值降低、乳酸升高和三羧酸循环中间产物减少，提示脑能量缺陷。外周生物标志物：包括电子传递链（ETC）复合物活性降低、MDA和8-OHdG升高、嘌呤能酶改变以及mtDNA升高，反映全身性生物能量应激。针对线粒体辅因子（肌酸、辅酶Q10、肉碱、NA C），代谢策略（生酮饮食）以及免疫调节或嘌呤能通路调节剂显示出前景。 结论：新出现的证据表明，全身性生物能量失调可能参与双相障碍（BD）的病理生理过程。将线粒体、代谢和炎症生物标志物与神经影像学整合，可能有助于实现基于生物学信息的患者分层和旨在恢复能量稳态的精准治疗。需要大规模、标准化的多中心研究来将这些发现转化为临床实践。
完整摘要 · 英文原文
BACKGROUND: Bipolar disorder (BD) is marked by recurrent mood episodes and functional impairment. Growing evidence implicates mitochondrial dysfunction, oxidative stress, and metabolic disturbances as important to its pathophysiology, affecting neuronal signalling, synaptic plasticity, and inflammatory pathways. AIMS: This review synthesises current evidence linking energetic metabolism to BD, integrates neuroimaging and peripheral biomarker findings, and discusses emerging therapeutic strategies targeting mitochondrial and metabolic dysfunction. METHODS: A systematic search following PRISMA guidelines was conducted across PubMed, MEDLINE, EMBASE, Scopus, and Cochrane Library using 'bipolar disorder', 'energetic metabolism', and 'mitochondria'. Inclusion criteria comprised peer-reviewed human studies, original research, and meta-analyses; paediatric, non-English, dietary, genetic, or comorbidity-focused studies were excluded. Additional manual searches targeted biomarker-specific studies. RESULTS: Evidence consistently shows impaired oxidative phosphorylation, reduced ATP and phosphocreatine, altered NAD+/NADH ratios, and increased oxidative and inflammatory markers in BD. Neuroimaging demonstrates reduced PCr/ATP ratios, elevated lactate, and decreased TCA cycle intermediates, indicating cerebral energy deficits. Peripheral biomarkers: including decreased ETC complex activity, increased MDA and 8-OHdG, altered purinergic enzymes, and elevated mtDNA reflect systemic bioenergetic stress. Emerging interventions targeting mitochondrial cofactors (creatine, CoQ10, carnitine, NAC), metabolic strategies (ketogenic diet), and immunomodulatory or purinergic pathway modulators show promise. CONCLUSIONS: Emerging evidence suggests that systemic bioenergetic dysregulation may contribute to the pathophysiology of BD. Integrating mitochondrial, metabolic, and inflammatory biomarkers with neuroimaging may enable biologically informed patient stratification and precision therapeutics aimed at restoring energetic homeostasis. Large, standardised multicenter studies are required to translate these findings into clinical practice.