Departamento de Farmacología, Facultad de Medicina, Universidad Complutense, Centro de Investigación en red de Salud Mental, CIBERSAM-ISCIII, Instituto de Investigación Hospital 12 de Octubre, Madrid, Spain.
Int J Neuropsychopharmacol. 2010 Nov;13(10):1411-29. doi: 10.1017/S1461145710000970. Epub 2010 Aug 27.
The aetiology of psychiatric diseases such as depression or schizophrenia remains largely unknown, even though multiple theories have been proposed. Although monoamine theory is the cornerstone of available pharmacological therapies, relapses, incomplete control of symptoms or failure in treatment occur frequently. From an inflammatory/immune point of view, both entities share several common hallmarks in their pathophysiology, e.g. neuroendocrine/immune alterations, structural/functional abnormalities in particular brain areas, and cognitive deficits, suggesting a dysregulated inflammatory-related component of these diseases that better explains the myriad of symptoms presented by affected individuals. In this review we aimed to explore the role and relevance of inflammatory related lipids (prostanoids) derived from arachidonic acid metabolism by identification of new inflammatory markers and possible pharmacological/dietary modulation of these compounds, with the aim of improving some of the symptoms developed by individuals affected with psychiatric diseases (a critical review of basic and clinical studies about inflammatory-related arachidonic acid metabolism on neuropsychiatric diseases is included). As a specific candidate, one of these immunoregulatory lipids, the anti-inflammatory prostaglandin 15d-PGJ₂ and its nuclear receptor peroxisome proliferator-activated nuclear receptor (PPARγ) could be used as a biological marker for psychiatric diseases. In addition, its pharmacological activation can be considered as a multi-faceted therapeutic target due to its anti-inflammatory/antioxidant/anti-excitotoxic/pro-energetic profile, reported in some inflammatory-related scenarios (neurological and stress-related diseases). PPARs are activated by a great variety of compounds, the most relevant being the currently prescribed group of anti-diabetic drugs thiazolidinediones, and some cannabinoids (both endocannabinoids, phytocannabinoids or synthetic), as possible novel therapeutical strategy.
尽管已经提出了多种理论，但精神疾病（如抑郁症或精神分裂症）的病因仍在很大程度上未知。尽管单胺理论是现有药物治疗的基石，但经常会出现复发、症状控制不完全或治疗失败的情况。从炎症/免疫的角度来看，这两种疾病在其病理生理学上有几个共同的特征，例如神经内分泌/免疫改变、特定脑区的结构/功能异常和认知缺陷，这表明这些疾病存在炎症相关的失调成分，可以更好地解释受影响个体所表现出的众多症状。在这篇综述中，我们旨在通过识别新的炎症标志物并探讨炎症相关脂质（前列腺素）在精神疾病中的作用和相关性，以及这些化合物的可能药理学/饮食调节，从而探索炎症相关脂质（前列腺素）在精神疾病中的作用和相关性，以改善受精神疾病影响的个体所出现的一些症状（包括对神经精神疾病中炎症相关花生四烯酸代谢的基础和临床研究的批判性回顾）。作为一个特定的候选物，这些免疫调节脂质之一，抗炎性前列腺素 15d-PGJ₂及其核受体过氧化物酶体增殖物激活受体（PPARγ），可以作为精神疾病的生物标志物。此外，由于其在一些炎症相关情况下（神经和应激相关疾病）报告的抗炎/抗氧化/抗兴奋毒性/促能谱，其药理学激活可以被认为是一种多方面的治疗靶点。PPARs 被多种化合物激活，最相关的是目前开处方的一组抗糖尿病药物噻唑烷二酮类药物和一些大麻素（内源性大麻素、植物大麻素或合成大麻素），作为新的治疗策略。
