Cousins Center for Psychoneuroimmunology, University of California at Los Angeles, Los Angeles, CA, USA.
Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, Los Angeles, CA, USA.
Transl Psychiatry. 2021 Mar 15;11(1):167. doi: 10.1038/s41398-021-01268-z.
Inflammation plays a role in depression pathophysiology and treatment response, with effects varying by sex and therapeutic modality. Lower levels of interleukin(IL)-8 predict depression response to antidepressant medication and to electroconvulsive therapy (ECT), although ECT effects are specific to females. Whether IL-8 predicts depression response to ketamine and in a sex-specific manner is not known. Here, depressed patients (n = 46; female, n = 17) received open label infusion of ketamine (0.5 mg/kg over 40 min; NCT02165449). Plasma levels of IL-8 were evaluated at baseline and post-treatment. Baseline levels of IL-8 had a trending association with response to ketamine, depending upon sex (responder status × sex interaction: p = 0.096), in which lower baseline levels of IL-8 in females (p = 0.095) but not males (p = 0.96) trended with treatment response. Change in levels of IL-8 from baseline to post-treatment differed significantly by responder status (defined as ≥50% reduction in Hamilton Depression Rating Scale [HAM-D] Score), depending upon sex (responder status × sex × time interaction: F(1,42)=6.68, p = 0.01). In addition, change in IL-8 interacted with sex to predict change in HAM-D score (β = -0.63, p = 0.003); increasing IL-8 was associated with decreasing HAM-D score in females (p = 0.08) whereas the inverse was found in males (p = 0.02). Other inflammatory markers (IL-6, IL-10, tumor necrosis factor-α, C-reactive protein) were explored with no significant relationships identified. Given these preliminary findings, further evaluation of sex differences in the relationship between IL-8 and treatment response is warranted to elucidate mechanisms of response and aid in the development of personalized approaches to depression treatment.
炎症在抑郁症的病理生理学和治疗反应中起作用，其影响因性别和治疗方式而异。较低水平的白细胞介素 (IL)-8 预测抗抑郁药物和电惊厥治疗 (ECT) 对抑郁症的反应，但 ECT 的作用是女性特有的。IL-8 是否预测氯胺酮的抑郁症反应以及是否存在性别特异性尚不清楚。在这里，抑郁患者（n=46；女性，n=17）接受了氯胺酮的开放标签输注（0.5mg/kg 超过 40 分钟；NCT02165449）。在基线和治疗后评估了 IL-8 的血浆水平。IL-8 的基线水平与氯胺酮的反应呈趋势相关，这取决于性别（反应者状态×性别交互作用：p=0.096），其中女性的较低基线 IL-8 水平（p=0.095）但男性（p=0.96）与治疗反应呈趋势相关。从基线到治疗后的 IL-8 水平变化在反应者状态（定义为汉密尔顿抑郁评定量表[HAM-D]评分至少降低 50%）方面有显著差异，这取决于性别（反应者状态×性别×时间交互作用：F（1,42）=6.68，p=0.01）。此外，IL-8 的变化与性别相互作用，以预测 HAM-D 评分的变化（β=-0.63，p=0.003）；在女性中，IL-8 的增加与 HAM-D 评分的降低相关（p=0.08），而在男性中则相反（p=0.02）。还探讨了其他炎症标志物（IL-6、IL-10、肿瘤坏死因子-α、C 反应蛋白），但未发现有显著关系。鉴于这些初步发现，需要进一步评估 IL-8 与治疗反应之间的关系中的性别差异，以阐明反应机制，并帮助开发针对抑郁症的个性化治疗方法。
