Conceptual convergence: increased inflammation is associated with increased basal ganglia glutamate in patients with major depression.
Conceptual convergence: increased inflammation is associated with increased basal ganglia glutamate in patients with major depression.
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DOI：
10.1038/mp.2015.206
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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：
Haroon E;Fleischer CC;Felger JC;Chen X;Woolwine BJ;Patel T;Hu XP;Miller AH
炎症和谷氨酸代谢的改变是抑郁症病理生理学中的两个途径。有趣的是，这些途径可能是联系在一起的，因为给予炎性细胞因子如干扰素-α，以其他方式非抑郁对照增加了基底神经节和背侧前扣带皮层（dACC）中的谷氨酸盐，如磁共振波谱（MRS）所测量的。在重度抑郁症患者中，炎症增加是否与谷氨酸盐增加有关尚不清楚。因此，我们进行了一项横断面研究，50例无药物治疗的抑郁症门诊患者使用单体素MRS，以测量基底神经节和dACC中的绝对谷氨酸浓度。多体素化学位移成像（CSI）用于探索基底神经节中其他代谢物的肌酐标准化测量。沿着快感缺乏和精神发育速度，评估血浆和脑脊液（CSF）炎症标志物。在控制年龄、性别、种族、体重指数、吸烟状况和抑郁严重程度的情况下，血浆C反应蛋白（CRP）对数增加与左侧基底节谷氨酸对数增加显著相关。反过来，对数左基底神经节谷氨酸与手指敲击测试，简单反应时间任务和数字符号替换任务测量的快感缺乏和精神发育迟缓有关。血浆CRP与dACC谷氨酸无关。血浆和CSF CRP也与CSI测量的基底神经节谷氨酸和神经胶质标记物肌醇相关。这些数据表明，在重度抑郁症的炎症增加可能会导致增加谷氨酸在基底神经节与胶质细胞功能障碍，并建议针对谷氨酸的治疗策略可能是优先有效的抑郁症患者的炎症增加，通过CRP测量。
Inflammation and altered glutamate metabolism are two pathways implicated in the pathophysiology of depression. Interestingly, these pathways may be linked given that administration of inflammatory cytokines such as interferon-α to otherwise non-depressed controls increased glutamate in the basal ganglia and dorsal anterior cingulate cortex (dACC) as measured by magnetic resonance spectroscopy (MRS). Whether increased inflammation is associated with increased glutamate among patients with major depression is unknown. Accordingly, we conducted a cross-sectional study of 50 medication-free, depressed outpatients using single-voxel MRS, to measure absolute glutamate concentrations in basal ganglia and dACC. Multivoxel chemical shift imaging (CSI) was used to explore creatine-normalized measures of other metabolites in basal ganglia. Plasma and cerebrospinal fluid (CSF) inflammatory markers were assessed along with anhedonia and psychomotor speed. Increased log plasma C-reactive protein (CRP) was significantly associated with increased log left basal ganglia glutamate controlling for age, sex, race, body mass index, smoking status and depression severity. In turn, log left basal ganglia glutamate was associated with anhedonia and psychomotor slowing measured by the finger-tapping test, simple reaction time task and the Digit Symbol Substitution Task. Plasma CRP was not associated with dACC glutamate. Plasma and CSF CRP were also associated with CSI measures of basal ganglia glutamate and the glial marker myoinositol. These data indicate that increased inflammation in major depression may lead to increased glutamate in the basal ganglia in association with glial dysfunction and suggest that therapeutic strategies targeting glutamate may be preferentially effective in depressed patients with increased inflammation as measured by CRP.