Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia; Neuroscience Graduate Program, Graduate Division of Biological and Biomedical Sciences, Emory University, Atlanta, Georgia.
Biol Psychiatry. 2023 Mar 1;93(5):405-418. doi: 10.1016/j.biopsych.2022.11.003. Epub 2022 Nov 9.
Findings from numerous laboratories and across neuroimaging modalities have consistently shown that exogenous administration of cytokines or inflammatory stimuli that induce cytokines disrupts circuits and networks involved in motivation and motor activity, threat detection, anxiety, and interoceptive and emotional processing. While inflammatory effects on neural circuits and relevant behaviors may represent adaptive responses promoting conservation of energy and heightened vigilance during immune activation, chronically elevated inflammation may contribute to symptoms of psychiatric illnesses. Indeed, biomarkers of inflammation such as cytokines and acute phase reactants are reliably elevated in a subset of patients with unipolar or bipolar depression, anxiety-related disorders, and schizophrenia and have been associated with differential treatment responses and poor clinical outcomes. A growing body of literature also describes higher levels of endogenous inflammatory markers and altered, typically lower functional or structural connectivity within these circuits in association with transdiagnostic symptoms such as anhedonia and anxiety in psychiatric and at-risk populations. This review presents recent evidence that inflammation and its effects on the brain may serve as one molecular and cellular mechanism of dysconnectivity within anatomically and/or functionally connected cortical and subcortical regions in association with transdiagnostic symptoms. We also discuss the need to establish reproducible methods to assess inflammation-associated dysconnectivity in relation to behavior for use in translational studies or biomarker-driven clinical trials for novel pharmacological or behavioral interventions targeting inflammation or its effects on the brain.
来自众多实验室和各种神经影像学模式的研究结果一致表明，细胞因子的外源性给药或诱导细胞因子产生的炎症刺激会破坏参与动机和运动活动、威胁检测、焦虑以及内脏感觉和情绪处理的回路和网络。虽然炎症对神经回路和相关行为的影响可能代表了适应性反应，有助于在免疫激活期间节约能量和提高警惕，但慢性炎症升高可能导致精神疾病的症状。事实上，细胞因子和急性期反应物等炎症生物标志物在一部分单相或双相抑郁、焦虑相关障碍和精神分裂症患者中可靠升高，并与不同的治疗反应和不良临床结果相关。越来越多的文献还描述了在精神科和高危人群中与快感缺失和焦虑等跨诊断症状相关的内源性炎症标志物水平升高和这些回路中通常较低的功能或结构连接性。本综述介绍了最近的证据，表明炎症及其对大脑的影响可能是与跨诊断症状相关的解剖学和/或功能连接的皮质和皮质下区域内连接不良的一种分子和细胞机制。我们还讨论了需要建立可重复的方法来评估与行为相关的炎症相关连接不良，以便在针对炎症或其对大脑影响的新型药理学或行为干预的转化研究或基于生物标志物的临床试验中使用。
