Furey Maura L, Drevets Wayne C, Szczepanik Joanna, Khanna Ashish, Nugent Allison, Zarate Carlos A
Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute on Mental Health, National Institutes of Health, Bethesda, MD (Dr Furey, Ms Szczepanik, Dr Nugent, and Dr Zarate); Janssen Pharmaceuticals, LLC, of Johnson & Johnson, Inc., Titusville, NJ (Dr Drevets); Physical Medicine & Rehabilitation, Jewish Medical Center, Brooklyn Hospital Center, Brooklyn, NY (Dr Khanna).Registry number NCT00055575.
Int J Neuropsychopharmacol. 2015 Mar 28;18(8):pyv028. doi: 10.1093/ijnp/pyv028.
Faster acting antidepressants and biomarkers that predict treatment response are needed to facilitate the development of more effective treatments for patients with major depressive disorders. Here, we evaluate implicitly and explicitly processed emotional faces using neuroimaging to identify potential biomarkers of treatment response to the antimuscarinic, scopolamine.
Healthy participants (n=15) and unmedicated-depressed major depressive disorder patients (n=16) participated in a double-blind, placebo-controlled crossover infusion study using scopolamine (4 μg/kg). Before and following scopolamine, blood oxygen-level dependent signal was measured using functional MRI during a selective attention task. Two stimuli comprised of superimposed pictures of faces and houses were presented. Participants attended to one stimulus component and performed a matching task. Face emotion was modulated (happy/sad) creating implicit (attend-houses) and explicit (attend-faces) emotion processing conditions. The pretreatment difference in blood oxygen-level dependent response to happy and sad faces under implicit and explicit conditions (emotion processing biases) within a-priori regions of interest was correlated with subsequent treatment response in major depressive disorder.
Correlations were observed exclusively during implicit emotion processing in the regions of interest, which included the subgenual anterior cingulate (P<.02) and middle occipital cortices (P<.02).
The magnitude and direction of differential blood oxygen-level- dependent response to implicitly processed emotional faces prior to treatment reflect the potential to respond to scopolamine. These findings replicate earlier results, highlighting the potential for pretreatment neural activity in the middle occipital cortices and subgenual anterior cingulate to inform us about the potential to respond clinically to scopolamine.
需要作用更快的抗抑郁药和能够预测治疗反应的生物标志物,以促进为重度抑郁症患者开发更有效的治疗方法。在此,我们使用神经影像学评估对经过隐式和显式处理的情绪面孔,以识别对抗毒蕈碱药物东莨菪碱治疗反应的潜在生物标志物。
健康参与者(n = 15)和未用药的重度抑郁症患者(n = 16)参与了一项使用东莨菪碱(4μg/kg)的双盲、安慰剂对照交叉输注研究。在输注东莨菪碱之前和之后,在选择性注意力任务期间使用功能磁共振成像测量血氧水平依赖信号。呈现由面孔和房屋的叠加图片组成的两种刺激。参与者关注一种刺激成分并执行匹配任务。面孔情绪被调制(开心/悲伤),从而创建隐式(关注房屋)和显式(关注面孔)情绪处理条件。在预先设定的感兴趣区域内,隐式和显式条件下对开心和悲伤面孔的血氧水平依赖反应的预处理差异(情绪处理偏差)与重度抑郁症患者随后的治疗反应相关。
仅在感兴趣区域的隐式情绪处理过程中观察到相关性,这些区域包括膝下前扣带回(P <.02)和枕中皮质(P <.02)。
治疗前对隐式处理的情绪面孔的血氧水平依赖反应差异的大小和方向反映了对东莨菪碱反应的潜力。这些发现重复了早期结果,突出了枕中皮质和膝下前扣带回预处理神经活动对于告知我们临床上对东莨菪碱反应潜力的可能性。