There is critical need for a clinically useful tool to predict antidepressant treatment outcome in major depressive disorder (MDD) to reduce suffering and mortality. This analysis sought to build upon previously reported antidepressant treatment efficacy prediction from 2-[¹⁸F]-fluorodeoxyglucose - Positron Emission Tomography (FDG-PET) using metabolic rate of glucose uptake (MRGlu) from dynamic FDG-PET imaging with the goal of translation to clinical utility. This investigation is a randomized, double-blind placebo-controlled trial. All participants were diagnosed with MDD and received an FDG-PET scan before randomization and after treatment. Hamilton Depression Rating Scale (HDRS-17) was completed in participants diagnosed with MDD before and after 8 weeks of escitalopram, or placebo. MRGlu (mg/(min*100 ml)) was estimated within the raphe nuclei, right insula, and left ventral Prefrontal Cortex in 63 individuals. Linear regression was used to examine the association between pretreatment MRGlu and percent decrease in HDRS-17. Additionally, the association between percent decrease in HDRS-17 and percent change in MRGlu between pretreatment scan and post-treatment scan was examined. Covariates were treatment type (SSRI/placebo), handedness, sex, and age. Depression severity decrease (n = 63) was not significantly associated with pretreatment MRGlu in the raphe nuclei $(\beta$ = -2.61e^-03 [-0.26, 0.25], p = 0.98), right insula $(\beta$ = 0.05 [-0.23, 0.32], p = 0.72), or ventral prefrontal cortex $(\beta$ = 0.06 [-0.23, 0.34], p = 0.68) where $\beta$ is the standardized estimated coefficient, with a 95% confidence interval, or in whole brain voxelwise analysis (family-wise error correction, alpha = 0.05). MRGlu percent change was not significantly associated with depression severity decrease (n = 58) before multiple comparison correction in the RN $(\beta$ = 0.20 [-0.07, 0.47], p = 0.15), right insula $(\beta$ = 0.24 [-0.03, 0.51], p = 0.08), or vPFC $(\beta$ = 0.22 [-0.06, 0.50], p = 0.12). We propose that FDG-PET imaging does not indicate a clinically relevant biomarker of escitalopram or placebo treatment response in heterogeneous major depressive disorder cohorts. Future directions include focusing on potential biologically-based subtypes of major depressive disorder by implementing biomarker stratified designs.

迫切需要一种临床有用的工具来预测重度抑郁症 (MDD) 的抗抑郁治疗结果，以减少痛苦和死亡率。该分析试图建立在先前报道的 2-[ ¹⁸F]-氟脱氧葡萄糖 - 正电子发射断层扫描 (FDG-PET) 使用来自动态 FDG-PET 成像的葡萄糖摄取代谢率 (MRGlu)，目标是转化为临床应用。这项调查是一项随机、双盲安慰剂对照试验。所有参与者都被诊断出患有 MDD，并在随机分组前和治疗后接受了 FDG-PET 扫描。汉密尔顿抑郁量表（HDRS-17）在依他普仑或安慰剂治疗 8 周前后被诊断患有 MDD 的参与者完成。MRGlu (mg/(min*100 ml)) 在 63 个人的中缝核、右脑岛和左腹前额叶皮层内进行了估计。线性回归用于检查预处理 MRGlu 与 HDRS-17 降低百分比之间的关联。此外，检查了在治疗前扫描和治疗后扫描之间，HDRS-17 下降百分比与 MRGlu 变化百分比之间的关联。协变量是治疗类型（SSRI/安慰剂）、惯用手、性别和年龄。抑郁严重程度降低（n = 63）与中缝核中的预处理 MRGlu 没有显着相关性$(\beta$ = -2.61e ^-03 [-0.26, 0.25], p = 0.98)，右脑岛$(\beta$ = 0.05 [-0.23, 0.32], p = 0.72)，或腹侧前额叶皮层$(\beta$ = 0.06 [-0.23, 0.34], p = 0.68) 其中$\beta$是标准化的估计系数，具有 95% 的置信区间，或在全脑体素分析中（家庭误差校正，α = 0.05）。在 RN 进行多重比较校正之前，MRGlu 百分比变化与抑郁严重程度降低（n = 58）没有显着相关性$(\beta$ = 0.20 [-0.07, 0.47], p = 0.15)，右脑岛$(\beta$ = 0.24 [-0.03, 0.51]，p = 0.08)，或 vPFC$(\beta$ = 0.22 [-0.06, 0.50]，p = 0.12)。我们建议 FDG-PET 成像在异质性重度抑郁症队列中并不表明依他普仑或安慰剂治疗反应的临床相关生物标志物。未来的方向包括通过实施生物标志物分层设计来关注潜在的基于生物学的重度抑郁症亚型。