Institute of Cognitive Neuroscience, University College London, London, United Kingdom; email:
Nuffield Department of Clinical Neurosciences and Department of Experimental Psychology, Oxford University, Oxford, United Kingdom.
Annu Rev Pharmacol Toxicol. 2024 Jan 23;64:313-338. doi: 10.1146/annurev-pharmtox-022423-014645. Epub 2023 Aug 16.
Apathy is a disabling syndrome associated with poor functional outcomes that is common across a broad range of neurological and psychiatric conditions. Currently, there are no established therapies specifically for the condition, and safe and effective treatments are urgently needed. Advances in the understanding of motivation and goal-directed behavior in humans and animals have shed light on the cognitive and neurobiological mechanisms contributing to apathy, providing an important foundation for the development of new treatments. Here, we review the cognitive components, neural circuitry, and pharmacology of apathy and motivation, highlighting converging evidence of shared transdiagnostic mechanisms. Though no pharmacological treatments have yet been licensed, we summarize trials of existing and novel compounds to date, identifying several promising candidates for clinical use and avenues of future drug development.
冷漠是一种与功能不良结局相关的致残综合征，在广泛的神经和精神疾病中都很常见。目前，针对这种疾病尚无既定的治疗方法，迫切需要安全有效的治疗方法。人类和动物动机及目标导向行为研究的进展揭示了导致冷漠的认知和神经生物学机制，为新疗法的开发提供了重要基础。在这里，我们综述了冷漠和动机的认知成分、神经回路和药理学，突出了共享的跨诊断机制的一致性证据。尽管还没有获得任何药物治疗的许可，但我们总结了迄今为止现有和新型化合物的试验，确定了几种有前途的临床应用候选药物和未来药物开发途径。
