Emory Behavioral Immunology Program, Winship Cancer Center, Emory University, Atlanta, GA, 30322, USA.
Department of Psychiatry & Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, 30322, USA.
Transl Psychiatry. 2018 Sep 10;8(1):189. doi: 10.1038/s41398-018-0241-4.
Combined increases in peripheral inflammation and brain glutamate may identify a subtype of depression with distinct neuroimaging signatures. Two contrasting subgroups of depressed subjects-with and without combined elevations in plasma C-reactive protein (CRP) and basal ganglia glutamate (high and low CRP-Glu, respectively) were identified by hierarchical clustering using plasma CRP (indexing peripheral inflammation) and magnetic resonance spectroscopy (MRS)-based measurement of left basal ganglia glutamate. High CRP-Glu group status was associated with greater severity of anhedonia and cognitive and motor slowing. Local- and network-level measures of functional integrity were determined using brain oxygen level-dependent (BOLD)-oscillatory activity and graph theory. Greater decreases in concordance of oscillatory activity between neighboring voxels (Regional Homogeneity 'ReHo', p < 0.01) within the MRS volume-of-interest was associated with the High CRP-Glu subgroup. Using brain-wide, CRP-Glu ReHo contrast maps, a covariance network of 41 regions-of-interest (ROIs) with similar ReHo decreases was identified in the High CRP-Glu group and was located to brain structures previously implicated in depression. The 41-ROI network was further decomposed into four subnetworks. ReHo decreases within Subnetwork4-comprised of reward processing regions -was associated with anhedonia. Subnetwork4 ReHo also predicted decreased network integrity, which mediated the link between local ReHo and anhedonia in the Low but not High CRP-Glu group. These findings suggest that decreased ReHo and related disruptions in network integrity may reflect toxic effects of inflammation-induced increases in extrasynaptic glutamate signaling. Moreover, local BOLD oscillatory activity as reflected in ReHo might be a useful measure of target-engagement in the brain for treatment of inflammation-induced behaviors.
外周炎症和大脑谷氨酸的联合增加可能会识别出具有不同神经影像学特征的抑郁症亚型。通过使用血浆 C 反应蛋白（CRP）（外周炎症指标）和磁共振波谱（MRS）测量左基底节谷氨酸，对具有和不具有血浆 CRP 和基底节谷氨酸联合升高的抑郁患者（高 CRP-Glu 组和低 CRP-Glu 组）进行层次聚类，以确定两个对比鲜明的抑郁亚组。高 CRP-Glu 组的状态与快感缺失、认知和运动迟缓的严重程度增加有关。使用大脑血氧水平依赖（BOLD）-振荡活动和图论来确定局部和网络水平的功能完整性。与高 CRP-Glu 亚组相关的是，在 MRS 感兴趣区中，相邻体素之间的振荡活动一致性（区域同质性“ReHo”，p<0.01）的更大降低。使用大脑全范围的 CRP-Glu ReHo 对比图，在高 CRP-Glu 组中确定了与类似 ReHo 降低相关的 41 个感兴趣区（ROI）的协方差网络，并位于以前与抑郁症相关的大脑结构中。41-ROI 网络进一步分解为四个子网。子网 4 中包括奖励处理区域的 ReHo 降低与快感缺失有关。子网 4 的 ReHo 也预测了网络完整性的降低，这在低 CRP-Glu 组中，局部 ReHo 和快感缺失之间的联系中介，而在高 CRP-Glu 组中则没有。这些发现表明，ReHo 的降低以及网络完整性的相关破坏可能反映了炎症诱导的突触外谷氨酸信号增加的毒性作用。此外，如 ReHo 所反映的局部 BOLD 振荡活动可能是大脑中炎症诱导行为治疗的靶点结合的有用指标。
