BDNF, interleukin-6, and salivary cortisol levels in depressed patients treated with desvenlafaxine
BDNF, interleukin-6, and salivary cortisol levels in depressed patients treated with desvenlafaxine
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DOI：
10.1016/j.pnpbp.2013.09.016
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发表时间：
2014-01
影响因子：
5.6
通讯作者：
P. Ninan;R. Shelton;W. Bao;C. Guico-Pabia
中科院分区：
文献类型：
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作者：
P. Ninan;R. Shelton;W. Bao;C. Guico-Pabia
脑源性神经营养因子（BDNF）、白细胞介素(IL)-6和唾液皮质醇与抑郁症严重程度和治疗反应之间的关系在一项双盲、安慰剂对照试验中进行了评估，该试验采用50mg /d的地文拉法辛治疗重度抑郁症。方法6例MDD门诊患者随机分为双盲治疗组，分别给予地文拉法辛50mg /d或安慰剂（2:1）治疗。采用17项汉密尔顿抑郁量表（HAM-D17）评估基线严重程度；第12周的治疗反应基于ham - d17总分、反应和缓解状态。在基线和第12周收集唾液（皮质醇）和血液（BDNF, IL-6）样本进行生物标志物检测。计算基线时生物标志物之间以及基线时生物标志物与ham - d17总分之间的Spearman相关性。采用Logistic回归分析评估基线生物标志物水平是否能预测第12周的治疗反应，无论是否对基线ham - d17评分、治疗和地理区域进行调整。同样，采用协方差分析来评估基线疾病严重程度是否能预测第12周的生物标志物变化。结果共有427例患者接受了≥1剂量的研究药物，并进行了基线和≥1次治疗初期疗效评估。基线时，IL-6水平与BDNF呈弱相关性（Spearman相关系数[rs] = 0.120；P= 0.014），但基线生物标志物水平与基线ham - d17总分无显著相关性（所有rs的绝对值≤0.061）。与安慰剂相比，地文拉法辛50mg /d治疗显著降低了第12周基线时ham - d17总分（P= 0.006），但这三种潜在的生物标志物并不能预测治疗效果。从基线开始，任何生物标志物水平的变化与第12周ham - d17总分的变化之间没有显著相关性，无论是总体上还是在地文拉法辛组或安慰剂组（所有rs的绝对值为0.003-0.196）。基线水平的BDNF、IL-6和唾液皮质醇在第12周不能显著预测治疗反应。尽管在地文拉法辛组（13.7%）和安慰剂组（5.7%）之间BDNF的中位增加没有显著差异，但在基线时抑郁症较严重（HAM-D17≤22）的患者中，BDNF的增加明显大于抑郁症较轻（HAM-D17≤22）的患者（33.4% vs 4.3%；P= 0.003）。IL-6或唾液皮质醇没有类似的发现。在基线时，潜在生物标志物之间或生物标志物与疾病严重程度之间的关系很弱或没有关系。虽然基线生物标志物水平不能预测治疗反应，但在基线时抑郁症更严重的患者中，BDNF的改善明显更大。
BackgroundRelationships between brain-derived neurotrophic factor (BDNF), interleukin (IL)-6, and salivary cortisol and both depression severity and treatment response were assessed in patients enrolled in a double-blind, placebo-controlled trial of desvenlafaxine 50 mg/d for MDD.MethodsOutpatients with MDD were randomly assigned to 12 weeks of double-blind treatment with desvenlafaxine 50 mg/d or placebo (2:1). Baseline severity was assessed using the 17-item Hamilton Rating Scale for Depression (HAM-D17); treatment response at week 12 was based on HAM-D17total score and response and remission status. Saliva (cortisol) and blood (BDNF, IL-6) samples for biomarker assay were collected at baseline and week 12. Spearman correlations were calculated between the biomarkers at baseline, and between biomarkers and HAM-D17total score at baseline. Logistic regression analyses were used to assess whether baseline biomarker levels predicted treatment response at week 12, with and without adjustment for baseline HAM-D17score, treatment, and geographic region. Similarly, an analysis of covariance was used to assess whether baseline disease severity predicted biomarker change at week 12.ResultsA total of 427 patients who received ≥ 1 dose of study drug and had baseline and ≥ 1 on-therapy primary efficacy evaluations were included in the analysis. At baseline, there was a statistically significant although weak correlation between levels of IL-6 and BDNF (Spearman correlation coefficient [rs] = 0.120;P= 0.014), but no significant correlation between baseline biomarker levels and baseline HAM-D17total score (absolute value of all rs, ≤ 0.061). Desvenlafaxine 50 mg/d treatment significantly reduced HAM-D17total score from baseline at week 12 compared with placebo (P= 0.006), but the three potential biomarkers did not predict treatment effects. No significant correlations were observed between the change from baseline in any biomarker level and change in HAM-D17total score at week 12, either overall, or in desvenlafaxine or placebo groups (absolute value of all rs, 0.003–0.196). Baseline levels of BDNF, IL-6, and salivary cortisol did not significantly predict response to treatment at week 12. Although median increase in BDNF was not significantly different between desvenlafaxine (13.7%) and placebo (5.7%) groups, the increase was significantly greater (33.4% vs 4.3%;P= 0.003) in patients with more severe depression at baseline (HAM-D17> 22) vs those with less severe depression (HAM-D17≤ 22). No similar findings were observed for IL-6 or salivary cortisol.DiscussionWeak or no relationships were observed at baseline between the potential biomarkers or between biomarkers and disease severity. While baseline biomarker level did not predict treatment response, improvement in BDNF was significantly greater among patients who were more severely depressed at baseline.