Inflammation impacts basal ganglia motor circuitry in association with psychomotor retardation, a key symptom of major depression (MD). We previously reported associations between circulating protein inflammatory biomarkers and psychomotor slowing as measured by neuropsychological tests probing psychomotor speed in patients with MD. To discover novel transcriptional signatures in peripheral blood immune cells related to psychomotor slowing, microarray data were analyzed in a primary cohort of 88 medically-stable, unmedicated, ambulatory MD patients. Results were confirmed and extended in a second cohort of 57 patients with treatment resistant depression (TRD) before and after anti-inflammatory challenge with the tumor necrosis factor antagonist infliximab versus placebo. Composite scores reflecting pure motor and cognitive-motor processing speed were linearly associated with 403 and 266 gene transcripts in each cohort, respectively (|R| > 0.30, p < 0.01), that were enriched for cytokine signaling and glycolysis-related pathways (p < 0.05). Unsupervised clustering in the primary cohort revealed two psychomotor slowing-associated gene co-expression modules that were enriched for interferon, interleukin-6, aerobic glycolysis, and oxidative phosphorylation pathways (p < 0.05, q < 0.1). Transcripts were predominantly derived from monocytes, plasmacytoid dendritic cells, and natural killer cells (p’s < 0.05). In infliximab-treated TRD patients with high plasma C-reactive protein concentrations (>5 mg/L), two differential co-expression modules enriched for oxidative stress and mitochondrial degradation were associated with improvements in psychomotor reaction time (p < 0.05). These results indicate that inflammatory signaling and associated metabolic reprogramming in peripheral blood immune cells are associated with systemic inflammation in depression and may affect relevant brain circuits to promote psychomotor slowing.

炎症影响与精神运动迟缓相关的基底神经节运动回路，这是重度抑郁症 (MD) 的一个关键症状。我们之前报道了循环蛋白炎症生物标志物与精神运动减慢之间的关联，这是通过神经心理学测试探测 MD 患者的精神运动速度来衡量的。为了发现与精神运动减慢相关的外周血免疫细胞中的新转录特征，在 88 名医学稳定、未接受药物治疗的门诊 MD 患者的主要队列中分析了微阵列数据。在使用肿瘤坏死因子拮抗剂英夫利昔单抗与安慰剂进行抗炎攻击前后的 57 名难治性抑郁症 (TRD) 患者的第二队列中，结果得到证实和扩展。R| > 0.30，p  < 0.01)，它们富含细胞因子信号转导和糖酵解相关通路 ( p  < 0.05)。主要队列中的无监督聚类揭示了两个精神运动减慢相关基因共表达模块，这些模块富含干扰素、白细胞介素 6、有氧糖酵解和氧化磷酸化途径 ( p  < 0.05，q  < 0.1)。转录本主要来源于单核细胞、浆细胞样树突状细胞和自然杀伤细胞（p< 0.05）。在接受英夫利昔单抗治疗的高血浆 C 反应蛋白浓度 (>5 mg/L) 的 TRD 患者中，两种富含氧化应激和线粒体降解的差异共表达模块与精神运动反应时间的改善相关 ( p  < 0.05)。这些结果表明，外周血免疫细胞中的炎症信号和相关的代谢重编程与抑郁症的全身炎症有关，并可能影响相关的脑回路以促进精神运动减慢。