Inflammation is associated with the development of anhedonia in major depression (MD), but the pathway by which inflammatory molecules gain access to the brain and lead to anhedonia is not clear. Molecules of the kynurenine pathway (KP), which is activated by inflammation, readily influx into the brain and generate end products that alter brain chemistry, disrupt circuit functioning, and result in the expression of inflammatory behaviors such as anhedonia. We examined the impact of plasma and CSF KP metabolites on brain chemistry and neural function using multimodal neuroimaging in 49 depressed subjects. We measured markers of glial dysfunction and distress including glutamate (Glu) and myo-inositol in the left basal ganglia using magnetic resonance spectroscopy (MRS); metrics of local activity coherence (regional homogeneity, ReHo) and functional connectivity from resting-state functional MRI measures; and anhedonia from the Inventory for Depressive Symptoms-Self Report Version (IDS-SR). Plasma kynurenine/tryptophan (KYN/TRP) ratio and cerebrospinal fluid (CSF) 3-hydroxykynurenine (3HK) were associated with increases in left basal ganglia myo-inositol. Plasma kynurenic acid (KYNA) and KYNA/QA were associated with decreases and quinolinic acid (QA) with increases in left basal ganglia Glu. Plasma and CSF KP were associated with decreases in ReHo in the basal ganglia and dorsomedial prefrontal regions (DMPFC) and impaired functional connectivity between these two regions. DMPFC-basal ganglia mediated the effect of plasma and CSF KP on anhedonia. These findings highlight the pathological impact of KP system dysregulation in mediating inflammatory behaviors such as anhedonia.

炎症与重度抑郁症（MD）快感缺乏的发生有关，但炎症分子进入大脑并导致快感缺乏的途径尚不清楚。被炎症激活的犬尿氨酸通路（KP）分子很容易流入大脑并产生最终产物，改变大脑化学成分，扰乱回路功能，并导致快感缺乏等炎症行为的表现。我们使用多模式神经影像学检查了 49 名抑郁症受试者的血浆和脑脊液 KP 代谢物对大脑化学和神经功能的影响。我们使用磁共振波谱 (MRS) 测量了左侧基底神经节中神经胶质功能障碍和痛苦的标志物，包括谷氨酸 (Glu) 和肌醇；静息态功能 MRI 测量的局部活动一致性（区域均匀性，ReHo）和功能连接性指标；和快感缺乏来自抑郁症状清单-自我报告版本（IDS-SR）。血浆犬尿氨酸/色氨酸 (KYN/TRP) 比率和脑脊液 (CSF) 3-羟基犬尿氨酸 (3HK) 与左基底节肌醇增加相关。血浆犬尿酸 (KYNA) 和 KYNA/QA 与左基底神经节 Glu 的减少相关，喹啉酸 (QA) 与左基底节 Glu 的增加相关。血浆和脑脊液 KP 与基底神经节和背内侧前额叶区域 (DMPFC) 的 ReHo 减少以及这两个区域之间的功能连接受损有关。DMPFC-基底神经节介导血浆和脑脊液 KP 对快感缺失的影响。这些发现强调了 KP 系统失调在介导快感缺乏等炎症行为中的病理影响。