Neurochemical, Neurocircuitry, and Psychopathological Mechanisms of PTSD: Emerging Pharmacotherapies and Clinical Perspectives.

IF 4.1 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

ACS Chemical Neuroscience Pub Date : 2025-06-10 DOI:10.1021/acschemneuro.5c00335

Santosh Kumar Prajapati, Shreyasi Majumdar, Snehapriya Murari, Kirti MachhindraVadak, Sairam Krishnamurthy

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引用次数: 0

Abstract

Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition triggered by exposure to traumatic events, with complex neurobiological anomalies that remain incompletely understood. This review aims to comprehensively explore the neurocircuitry, neurochemical dysregulation, and emerging pharmacological targets associated with PTSD, offering a consolidated framework for developing more effective treatments. Particular emphasis is employed on the role of the hypothalamic-pituitary-adrenal (HPA) axis, monoamines, glutamate, GABAergic, and the orexinergic system, as well as emerging therapeutic agents such as 3,4-methylenedioxymethamphetamine (MDMA), ketamine, suvorexant, and cannabinoid modulators. Psychotherapeutic approaches including cognitive-behavioral therapy (CBT) and prolonged exposure therapy are also discussed in the context of their neurobiological effects. Articles were identified through a structured search in PubMed, Scopus, and Google Scholar, focusing on English-language publications from 1950 to 2025. Inclusion criteria encompassed original research, clinical trials, and reviews relevant to PTSD mechanisms and treatment. By integrating recent findings, this review advances the understanding of PTSD pathophysiology and highlights potential avenues for targeted, personalized therapies, thereby contributing to clinical and translational research in neuropsychiatry.

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创伤后应激障碍的神经化学、神经回路和精神病理机制：新兴药物治疗和临床观点。

创伤后应激障碍（PTSD）是一种因暴露于创伤性事件而引发的使人衰弱的精神疾病，具有复杂的神经生物学异常，目前尚未完全了解。本文旨在全面探讨与创伤后应激障碍相关的神经回路、神经化学失调和新出现的药理学靶点，为开发更有效的治疗方法提供一个统一的框架。特别强调下丘脑-垂体-肾上腺（HPA）轴，单胺，谷氨酸，gaba能和食欲能系统的作用，以及新兴的治疗剂，如3,4-亚甲基二氧甲基苯丙胺（MDMA），氯胺酮，强效剂和大麻素调节剂。心理治疗方法包括认知行为疗法（CBT）和长时间暴露疗法也在其神经生物学作用的背景下进行了讨论。文章是通过在PubMed、Scopus和b谷歌Scholar中进行结构化搜索确定的，重点是1950年至2025年的英语出版物。纳入标准包括与创伤后应激障碍机制和治疗相关的原始研究、临床试验和综述。通过整合最近的发现，本综述促进了对PTSD病理生理学的理解，并强调了有针对性的个性化治疗的潜在途径，从而为神经精神病学的临床和转化研究做出了贡献。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Chemical Neuroscience BIOCHEMISTRY & MOLECULAR BIOLOGY-CHEMISTRY, MEDICINAL

CiteScore

9.20

自引率

4.00%

发文量

323

审稿时长

1 months

期刊介绍： ACS Chemical Neuroscience publishes high-quality research articles and reviews that showcase chemical, quantitative biological, biophysical and bioengineering approaches to the understanding of the nervous system and to the development of new treatments for neurological disorders. Research in the journal focuses on aspects of chemical neurobiology and bio-neurochemistry such as the following: Neurotransmitters and receptors Neuropharmaceuticals and therapeutics Neural development—Plasticity, and degeneration Chemical, physical, and computational methods in neuroscience Neuronal diseases—basis, detection, and treatment Mechanism of aging, learning, memory and behavior Pain and sensory processing Neurotoxins Neuroscience-inspired bioengineering Development of methods in chemical neurobiology Neuroimaging agents and technologies Animal models for central nervous system diseases Behavioral research