Inflammation is associated with decreased functional connectivity within corticostriatal reward circuitry in depression.
Inflammation is associated with decreased functional connectivity within corticostriatal reward circuitry in depression.
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DOI：
10.1038/mp.2015.168
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发表时间：
2016-10
影响因子：
11
通讯作者：
Miller AH
中科院分区：
文献类型：
--
作者：
Felger JC;Li Z;Haroon E;Woolwine BJ;Jung MY;Hu X;Miller AH
抑郁症与皮质纹状体奖赏回路的改变有关。可能推动这些变化的一个病理生理途径是炎症。炎症的生物标志物(例如，细胞因子和C反应蛋白(CRP))在抑郁症患者中可靠地升高。此外，给予炎性刺激会减少与奖励相关的大脑区域的神经活动和多巴胺释放，这与动力减弱和快感丧失有关。因此，我们检查了抑郁症患者炎症增加是否会影响皮质纹状体奖赏回路，从而导致动机和目标导向运动行为的缺陷。对48例病情稳定、未服药的重度抑郁症患者进行了静息状态功能磁共振成像。使用与动机和运动控制相关的腹侧和背侧纹状体的种子，研究了全脑、体素方向的功能连接作为CRP的功能。C反应蛋白的升高与腹侧纹状体和前额叶腹侧皮质之间的连通性降低相关(校正P<；0.05)，后者又与快感缺乏的增加相关(R=−0.47，P=0.001)。C反应蛋白升高与运动速度减慢(R=0.31~0.45，P<0.0 5)和精神运动减慢(R=−0.35，P=0.015)相关。值得注意的是，中介分析显示，CRP对连接性的这些影响中介了CRP与快感缺失和运动减慢之间的显著关系。最后，纹状体和vmPFC之间的连接与血浆IL-6、IL-1β和IL-1受体拮抗剂的增加有关(R=−0.33~−0.36，P<；0.05)。这些发现表明，皮质纹状体连接性降低可能成为抗炎或前多巴胺能治疗策略的靶点，以改善包括抑郁在内的炎症增加患者的动机和运动障碍。
Depression is associated with alterations in corticostriatal reward circuitry. One pathophysiological pathway that may drive these changes is inflammation. Biomarkers of inflammation (for example, cytokines and C-reactive protein (CRP)) are reliably elevated in depressed patients. Moreover, administration of inflammatory stimuli reduces neural activity and dopamine release in reward-related brain regions in association with reduced motivation and anhedonia. Accordingly, we examined whether increased inflammation in depression affects corticostriatal reward circuitry to lead to deficits in motivation and goal-directed motor behavior. Resting-state functional magnetic resonance imaging was conducted on 48 medically stable, unmedicated outpatients with major depression. Whole-brain, voxel-wise functional connectivity was examined as a function of CRP using seeds for subdivisions of the ventral and dorsal striatum associated with motivation and motor control. Increased CRP was associated with decreased connectivity between ventral striatum and ventromedial prefrontal cortex (vmPFC) (corrected P<0.05), which in turn correlated with increased anhedonia (R=−0.47, P=0.001). Increased CRP similarly predicted decreased dorsal striatal to vmPFC and presupplementary motor area connectivity, which correlated with decreased motor speed (R=0.31 to 0.45, P<0.05) and increased psychomotor slowing (R=−0.35, P=0.015). Of note, mediation analyses revealed that these effects of CRP on connectivity mediated significant relationships between CRP and anhedonia and motor slowing. Finally, connectivity between striatum and vmPFC was associated with increased plasma interleukin (IL)-6, IL-1beta and IL-1 receptor antagonist (R=−0.33 to −0.36, P<0.05). These findings suggest that decreased corticostriatal connectivity may serve as a target for anti-inflammatory or pro-dopaminergic treatment strategies to improve motivational and motor deficits in patients with increased inflammation, including depression.