Seif Pegah
Harvard Medical School.
Beth Israel Deaconess Medical Center.
Clin Neuropsychiatry. 2025 Jun;22(3):229-242. doi: 10.36131/cnfioritieditore20250306.
Catatonia is a complex neuropsychiatric syndrome characterized by motor, cognitive, and emotional disturbances, affecting approximately 7-38% of psychiatric inpatients. Despite its prevalence, it is frequently underrecognized in clinical practice. The objective of this narrative review is to explore the hypothesis that dysfunction of the basal ganglia's indirect pathway-mediated by neurotransmitter imbalances-plays a central role in the pathophysiology of catatonia.
This narrative review synthesized clinical, neuroimaging, and preclinical studies identified through PubMed, Embase, and PsycINFO (1980-April 2025) using terms related to catatonia, basal ganglia pathways, and neurotransmitters. Studies on GABA, dopamine, glutamate, serotonin, and acetylcholine in catatonia or indirect pathway function were included. Findings were conceptually integrated to link neurotransmitter dysregulation with catatonic features, considering age-related effects and circuit models.
Evidence indicates that impaired inhibitory control within the indirect pathway is a core mechanism underlying catatonia. Key findings include reduced GABAergic tone, dopamine D2 receptor dysfunction, glutamatergic hyperactivity, and altered serotonergic and cholinergic modulation. These disruptions collectively contribute to clinical features such as stupor, rigidity, and stereotypies. While benzodiazepines, which enhance GABA-A receptor activity, remain the first-line treatment, preliminary evidence suggests that NMDA antagonists, dopamine agonists, and serotonergic/cholinergic modulators may also offer therapeutic benefits, though these are not yet widely implemented.
By integrating neurocircuit-based models with observed clinical phenomena, this review proposes a unifying framework to understand the neural basis of catatonia. Clarifying the role of indirect pathway dysfunction could support the development of targeted, mechanism-based interventions, ultimately improving recognition and treatment outcomes for this often-debilitating syndrome.
紧张症是一种复杂的神经精神综合征，其特征为运动、认知和情感障碍，约7% - 38%的精神科住院患者受其影响。尽管其患病率较高，但在临床实践中却常常未被充分认识。本叙述性综述的目的是探讨这样一种假说，即由神经递质失衡介导的基底神经节间接通路功能障碍在紧张症的病理生理学中起核心作用。
本叙述性综述综合了通过PubMed、Embase和PsycINFO（1980年 - 2025年4月）检索到的临床、神经影像学和临床前研究，使用了与紧张症、基底神经节通路和神经递质相关的术语。纳入了关于紧张症中γ-氨基丁酸（GABA）、多巴胺、谷氨酸、5-羟色胺（血清素）和乙酰胆碱或间接通路功能的研究。研究结果在概念上进行整合，以将神经递质失调与紧张症特征联系起来，同时考虑年龄相关影响和神经回路模型。
有证据表明，间接通路内抑制控制受损是紧张症的核心机制。主要发现包括GABA能张力降低、多巴胺D2受体功能障碍、谷氨酸能亢进以及血清素能和胆碱能调节改变。这些干扰共同导致了诸如木僵、僵硬和刻板行为等临床特征。虽然增强GABA - A受体活性的苯二氮䓬类药物仍然是一线治疗药物，但初步证据表明，N-甲基-D-天冬氨酸（NMDA）拮抗剂、多巴胺激动剂以及血清素能/胆碱能调节剂也可能具有治疗益处，尽管这些尚未广泛应用。
通过将基于神经回路的模型与观察到的临床现象相结合，本综述提出了一个统一框架来理解紧张症的神经基础。阐明间接通路功能障碍的作用有助于开发有针对性的、基于机制的干预措施，最终改善对这种常使人衰弱的综合征的识别和治疗效果。
