Objective: There is increasing evidence for a subgroup of major depressive disorder (MDD) associated with heightened peripheral blood inflammatory markers. In this study, the authors sought to understand the mechanistic brain-immune axis in inflammation-linked depression by investigating associations between functional connectivity (FC) of brain networks and peripheral inflammation in depression. Methods: Resting-state functional magnetic resonance imaging (fMRI) and peripheral blood immune marker data (C-reactive protein; CRP, interleukin-6; IL-6 and immune cells) were collected on N=46 healthy controls (HC; CRP ≤ 3mg/L) and N=83 cases of MDD, stratified further into low CRP (loCRP MDD; ≤ 3 mg/L; N=50) and high CRP (hiCRP MDD; > 3 mg/L; N=33). In a two-part analysis, network-based statistics (NBS) was firstly performed to ascertain FC differences via HC vs hiCRP MDD comparison. Association between this network of interconnected brain regions and peripheral CRP (N=83), IL-6 (N=72), neutrophils and CD4+ T-cells (N=36) were then examined in MDD cases only. Results: Case-control NBS testing revealed a single network of abnormally attenuated FC in hiCRP MDD, chiefly comprising default mode network (DMN) and ventral attentional network (VA) coupled regions, anatomically connecting the insula/frontal-operculum and posterior cingulate cortex (PCC). Across all MDD cases, FC within the identified network scaled negatively with CRP, IL-6 and neutrophils. Conclusions: The findings suggest that inflammation is associated with attenuation of functional connectivity within a brain network deemed critical for interoceptive signalling, e.g. accurate communication of peripheral bodily signals such as immune states to the brain, with implications for the etiology of inflammation-linked depression. keywords: functional connectivity, network-based statistics, peripheral inflammation, immune cells, depression.

中文翻译：

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脑功能网络的连通性不佳与抑郁症中的血液炎症标志物有关

目的：越来越多的证据表明，伴有外周血炎性标志物升高的重度抑郁症（MDD）亚组。在这项研究中，作者试图通过研究大脑网络的功能连接性（FC）与抑郁症周围炎症之间的联系来了解炎症相关性抑郁症的机械性脑免疫轴。方法：在N = 46名健康对照者（HC； CRP≤ 3 mg / L）和N = 83例MDD，进一步分为低CRP（loCRP MDD;≤3 mg / L; N = 50）和高CRP（hiCRP MDD;> 3 mg / L; N = 33）。在两部分的分析中，首先进行基于网络的统计（NBS），以通过HC与hiCRP MDD比较来确定FC差异。然后仅在MDD病例中检查此互连的大脑区域网络与周围CRP（N = 83），IL-6（N = 72），中性粒细胞和CD4 + T细胞（N = 36）之间的关联。结果：病例对照NBS测试显示，hiCRP MDD中单个衰减异常FC的网络，主要包括默认模式网络（DMN）和腹侧注意网络（VA）耦合区域，解剖上连接了岛突/额-和后扣带回皮质（ PCC）。在所有MDD病例中，确定的网络中的FC与CRP，IL-6和中性粒细胞呈负比例关系。结论：研究结果表明，炎症与认为对感知信号至关重要的大脑网络内部功能连通性的减弱有关，例如，外围身体信号（如对大脑的免疫状态）的准确传达，这与炎症相关性抑郁症的病因有关。关键词：功能连接性，基于网络的统计数据，外周炎症，免疫细胞，抑郁症。