Altinay Murat, Karne Harish, Beall Erik, Anand Amit
From the Center for Behavioral Health, Cleveland Clinic Foundation, Cleveland, OH.
J Clin Psychopharmacol. 2016 Dec;36(6):562-571. doi: 10.1097/JCP.0000000000000600.
This study investigated extended release quetiapine (quetiapine XR) associated changes in functional MRI (fMRI) measures of task-induced amygdalar activation and resting state connectivity in anxious unipolar major depressive disorder (AMDD).
Anxious unipolar major depressive disorder patients (n = 15) (17-item Hamilton Depression Rating Scale (HAM-D) >18 and Hamilton Anxiety Scale (HAM-A) >18) and closely matched healthy control (HC) subjects were compared at baseline for task induced amygdala activation and resting state connectivity on fMRI. Subsequently, AMDD patients were treated for 8 weeks with open-label quetiapine XR. Weekly HAM-D and HAM-A ratings were obtained, and the fMRI scan was repeated at weeks 2 and 8. Changes in fMRI measures were calculated using repeated-measures analysis of variance and correlation with decrease in HAM-D and HAM-A scores was examined.
At baseline, AMDD compared with HC exhibited increased task-induced left amygdalar activation (P = 0.05 clusterwise corrected) and decreased resting state amygdala-cortical and amygdala-pons connectivity (P < 0.05 clusterwise corrected). Quetiapine XR treatment was associated with significant decrease in HAM-D (df = 1,28; female [F] = 39; P = 0.001) and HAM-A scores (df = 1,28; F = 55; P = 0.001). The AMDD group showed increased amygdala-cortical connectivity (P < 0.05 [clusterwise corrected]) at week 2, which was maintained at week 8. At week 8, additional areas showed increased connectivity including insula and putamen. At 8 weeks, decrease in HAM-D scores correlated with increase in amygdala-mid cingulate and amygdala-cuneus connectivity (P = 0.05 [clusterwise corrected]). Decrease in HAM-A scores correlated with increase in amygdala-cuneus and parietal cortex connectivity (P = 0.05 [clusterwise corrected]).
Small sample-size, open-label single-arm design, HC only tested at baseline, focused only on amygdala.
Quetiapine XR effects in the treatment of AMDD are associated with modulation of amygdala connectivity.
本研究调查了缓释喹硫平（quetiapine XR）对单相重度焦虑抑郁障碍（AMDD）患者任务诱导杏仁核激活的功能磁共振成像（fMRI）测量值及静息态连接性的影响。
比较单相重度焦虑抑郁障碍患者（n = 15）（17项汉密尔顿抑郁量表（HAM-D）>18且汉密尔顿焦虑量表（HAM-A）>18）和匹配良好的健康对照（HC）受试者在基线时fMRI上任务诱导的杏仁核激活及静息态连接性。随后，单相重度焦虑抑郁障碍患者接受开放标签的喹硫平XR治疗8周。每周获取HAM-D和HAM-A评分，并在第2周和第8周重复进行fMRI扫描。使用重复测量方差分析计算fMRI测量值的变化，并检验其与HAM-D和HAM-A评分降低的相关性。
在基线时，与健康对照相比，单相重度焦虑抑郁障碍患者表现出任务诱导的左侧杏仁核激活增加（聚类校正P = 0.05），以及静息态杏仁核-皮质和杏仁核-脑桥连接性降低（聚类校正P < 0.05）。喹硫平XR治疗与HAM-D（自由度= 1,28；女性[F]= 39；P = 0.001）和HAM-A评分（自由度= 1,28；F = 55；P = 0.001）的显著降低相关。单相重度焦虑抑郁障碍组在第2周时杏仁核-皮质连接性增加（聚类校正P < 0.05），并在第8周维持。在第8周时，其他区域包括岛叶和壳核的连接性也增加。在第8周时，HAM-D评分的降低与杏仁核-中扣带回和杏仁核-楔叶连接性的增加相关（聚类校正P = 0.05）。HAM-A评分的降低与杏仁核-楔叶和顶叶皮质连接性的增加相关（聚类校正P = 0.05）。
样本量小、开放标签单臂设计、健康对照仅在基线时进行测试、仅关注杏仁核。
喹硫平XR治疗单相重度焦虑抑郁障碍的效果与杏仁核连接性的调节有关。
