Neutrophil to lymphocyte ratio and antidepressant treatment response in patients with major depressive disorder: Effect of sex and hippocampal volume

Several factors may affect response to treatment in Major Depressive Disorder (MDD) including immune/inflammatory alterations and regional brain volumes, particularly in hippocampal regions which have shown to be influenced by inflammatory status. Neutrophil-to-lymphocyte ratio (NLR) is an inflammatory marker found to be elevated in depressed women in large population studies. Here we investigate the effect of NLR on treatment response in MDD patients, and the role of sex and hippocampal volume on influencing this relationship. A sample of 124 MDD depressed inpatients (F = 80) underwent MRI acquisition, admission NLR was calculated by dividing absolute neutrophil by absolute lymphocyte counts and depression severity was assessed at admission and discharge via the Hamilton Depression Rating Scale (HDRS). As a measure of treatment response, delta HDRS was calculated. We found a significant moderation effect of sex on the relationship between NLR and Delta HDRS: a negative relation was found in females and a positive one in males. NLR was found to negatively affect hippocampal volumes in females. Both left and right hippocampal volume positively associated with Delta HDRS. Finally, left hippocampal volume mediated the effect of NLR on Delta HDRS in females. Sex moderated the relation between inflammation and treatment response in line with previous reports linking inflammation to hampered antidepressant effect in females. Further, this effect is partially mediated by hippocampal volume, suggesting that antidepressant response may be hampered by the detrimental effect of inflammation on the brain.重度抑郁症（Major Depressive Disorder, MDD）的治疗应答受多种因素影响，包括免疫/炎症改变与脑区体积变化，其中海马脑区（hippocampal regions）的体积已被证实受炎症状态调控。中性粒细胞与淋巴细胞比值（Neutrophil-to-lymphocyte ratio, NLR）作为一种炎症标志物，多项大样本人群研究显示抑郁女性的该指标水平显著升高。本研究旨在探讨中性粒细胞与淋巴细胞比值对重度抑郁症患者治疗应答的影响，以及性别与海马体积对该关联的调节作用。本研究纳入124名重度抑郁症住院患者（女性80例），所有受试者均接受磁共振成像（MRI）扫描；入院时通过绝对中性粒细胞计数除以绝对淋巴细胞计数计算中性粒细胞与淋巴细胞比值，并分别于入院时与出院时采用汉密尔顿抑郁量表（Hamilton Depression Rating Scale, HDRS）评估抑郁严重程度，以汉密尔顿抑郁量表减分（delta HDRS）作为治疗应答的评估指标。研究结果显示：性别对中性粒细胞与淋巴细胞比值与delta HDRS之间的关联存在显著调节效应，女性群体中二者呈负相关，男性群体中则呈正相关；女性群体中，中性粒细胞与淋巴细胞比值对海马体积存在显著负向影响；左右两侧海马体积均与delta HDRS呈正相关。进一步分析表明，女性群体的左侧海马体积在中性粒细胞与淋巴细胞比值对delta HDRS的影响中发挥中介作用。本研究中性别对炎症与治疗应答的调节效应与既往研究一致，后者证实炎症会削弱女性的抗抑郁治疗效果。此外，该调节效应部分通过海马体积介导，提示炎症对脑组织的损害作用可能会削弱抗抑郁治疗的应答效果。