University of Toronto, Department of Pharmacology & Toxicology, Canada; Sunnybrook Research Institute, Hurvitz Brain Sciences Program, Canada; University Health Network Toronto Rehabilitation Institute, Canada.
University Health Network Toronto Western Research Institute, Mood Disorders Psychopharmacology Unit, Canada; University of Toronto, Department of Psychiatry, Canada.
Neurosci Biobehav Rev. 2016 May;64:148-66. doi: 10.1016/j.neubiorev.2016.02.017. Epub 2016 Feb 23.
Evidence supports inflammatory involvement in mood and cognitive symptoms across psychiatric, neurological and medical disorders; however, inflammation is not a sensitive or specific characteristic of these diagnoses. The National Institute of Mental Health Research Domain Criteria (RDoC) ask for a shift away from symptom-based diagnoses toward a transdiagnostic neurobiological focus in the study of brain illnesses. The RDoC matrix may provide a useful framework for integrating the effects of inflammation on brain function. Based on preclinical and clinical findings, relevant relationships span negative and positive valence systems, cognitive systems, systems for social processes and arousal/regulatory systems. As an exemplar, we consider the psychopathological domain of anhedonia, conceptualizing the relevance of inflammation (e.g., cellular immunity) and downstream processes (e.g., indoleamine 2,3-dioxygenase activation and oxidative inactivation of tetrahydrobiopterin) across RDoC units of analysis (e.g., catecholamine neurotransmitter molecules, nucleus accumbens medium spiny neuronal cells, dopaminergic mesolimbic and mesocortical reward circuits, animal paradigms, etc.). We discuss implications across illnesses affecting the brain, including infection, major depressive disorder, stroke, Alzheimer's disease and type 2 diabetes.
有证据表明，炎症与精神、神经和内科疾病的情绪和认知症状有关；然而，炎症并不是这些诊断的敏感或特异性特征。美国国立精神卫生研究院的研究领域标准（RDoC）要求从基于症状的诊断转向对大脑疾病进行跨诊断的神经生物学研究。RDoC 矩阵可能为整合炎症对大脑功能的影响提供一个有用的框架。基于临床前和临床研究发现，相关关系涵盖了负性和正性效价系统、认知系统、社会过程系统和唤醒/调节系统。作为一个范例，我们考虑了快感缺失的精神病理学领域，将炎症（如细胞免疫）及其下游过程（如吲哚胺 2,3-双加氧酶的激活和四氢生物蝶呤的氧化失活）的相关性概念化，涉及 RDoC 分析单元（如儿茶酚胺神经递质分子、伏隔核中间神经元、多巴胺能边缘和皮质奖励回路、动物模型等）。我们讨论了影响大脑的各种疾病的影响，包括感染、重度抑郁症、中风、阿尔茨海默病和 2 型糖尿病。
