Kranzler Henry R, Stone Annjanette, Schichman Steven A, Griffin L Michelle, Roggenkamp Hannah, Thase Michael E, Lynch Kevin G, Oslin David W
Kranzler, MD, Veterans Integrated Service Network 4, Mental Illness Research, Education and Clinical Center, Crescenz Veterans Affairs Medical Center and Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
Stone, Pharmacogenomics Analysis Laboratory, Central Arkansas Veterans Healthcare System, Little Rock, AR.
Psychopharmacol Bull. 2025 Jan 1;55(1):8-25.
Immunologic measures have been studied as predictors of who will respond to standard antidepressants. Two previous, small studies of pretreatment leukocyte mRNA expression levels of the cytokines macrophage migration inhibitory factor (MIF) and interleukin 1-beta (IL1-β) identified antidepressant treatment responders.
We tested these findings in 1,299 patients from the PRIME Care study, a multi-center pharmacogenetic depression treatment trial. Patients underwent 5 depression-symptom assessments over 24 weeks. mRNA was extracted from peripheral blood, purified, and assayed with TaqMan gene expression assays and a known copy number calibrator to yield relative quantification and copy numbers for each sample. In generalized estimating equations models, we regressed the repeated depression measures and a binary treatment response measure on the baseline MIF and IL-1β measures and relevant covariates.
Participants' depression scores decreased monotonically during treatment, with the treatment response percentage increasing concomitantly. We found no significant associations of the cytokine concentrations with either the change in depression scores or the likelihood of a treatment response. A secondary analysis limited to a subsample of 126 participants selected to remove the potential for confounding also showed no significant associations.
Despite efforts to control for sample and assay method differences, these could have contributed to the lack of replication of prior research.
We did not replicate prior findings that pre-treatment expression levels for two cytokines predicted antidepressant treatment response. This raises questions about the clinical utility of using these biomarkers in treating depression.
免疫指标已被作为预测谁会对标准抗抑郁药产生反应的指标进行研究。此前两项关于细胞因子巨噬细胞移动抑制因子（MIF）和白细胞介素1-β（IL1-β）预处理白细胞mRNA表达水平的小型研究确定了抗抑郁治疗的反应者。
我们在PRIME Care研究中的1299名患者中验证了这些发现，该研究是一项多中心药物遗传学抑郁症治疗试验。患者在24周内接受了5次抑郁症状评估。从外周血中提取mRNA，进行纯化，并用TaqMan基因表达分析和已知拷贝数校准物进行检测，以得出每个样本的相对定量和拷贝数。在广义估计方程模型中，我们将重复的抑郁测量值和二元治疗反应测量值与基线MIF和IL-1β测量值及相关协变量进行回归分析。
参与者的抑郁评分在治疗期间单调下降，治疗反应百分比随之增加。我们发现细胞因子浓度与抑郁评分变化或治疗反应可能性之间均无显著关联。一项仅限于126名参与者的子样本的二次分析，旨在消除潜在的混杂因素，结果也显示无显著关联。
尽管努力控制样本和检测方法的差异，但这些差异可能导致了先前研究结果无法重复。
我们未能重复先前的研究结果，即两种细胞因子的预处理表达水平可预测抗抑郁治疗反应。这引发了关于在治疗抑郁症中使用这些生物标志物的临床实用性的问题。
