JAMA Psychiatry：神经活动或预测MDD患者对东莨菪碱的治疗反应

　　日前，《美国医学会杂志·精神病学》（JAMA Psychiatry）上发表的一项研究揭示，在严重抑郁障碍（MDD）的病理生理过程中有胆碱能和视觉加工功能障碍，并且视皮质区的神经反应，尤其是对情感刺激的反应可为鉴别能从东莨菪碱治疗中获益的患者提供一种有用的生物标记。

　　MDD患者急需改善治疗选择。起效更快的抗抑郁药和能预测临床反应的生物标记会促进治疗。东莨菪碱可产生快速的抗抑郁疗效并因此为在短期内确定治疗反应潜在生物标记的特征提供了机会。

　　该研究旨在确定在MDD患者中，当加工情感信息时基线大脑活动情况能否预测患者对东莨菪碱的治疗反应。

　　该研究为一项双盲、安慰剂对照的交叉研究，研究人员令参与者在执行面部识别和面部情感工作记忆任务时重复获取功能性磁共振成像图像。

　　研究共纳入15名当前抑郁症门诊患者和21名健康参与者，患者纳入标准：符合复发性MDD的DSM-IV标准，年龄18 到55岁。

　　将患者对东莨菪碱治疗反应的量值与血氧水平相关联，即与每一个识别与情感任务工作记忆组成部分（编码、维持和检验）相关的依赖（BOLD）信号相关联。治疗反应也与BOLD反应中的改变有关。对比健康与MDD患者组的基线神经活动。

　　结果显示，双侧中间枕叶皮质的基线BOLD反应，在情感工作记忆任务的刺激—加工组成部分期间，选择性地与治疗反应量值相关。在执行相同的任务条件时，应用东莨菪碱后，BOLD反应在中间枕叶皮质区重叠区域的改变也与临床反应有关。在基线期间，健康对照组在相同视觉区域的神经活动高于MDD组患者。

Potential of Pretreatment Neural Activity in the Visual Cortex During Emotional Processing to Predict Treatment Response to Scopolamine in Major Depressive Disorder

Context  

The need for improved treatment options for patients with major depressive disorder (MDD) is critical. Faster-acting antidepressants and biomarkers that predict clinical response will facilitate treatment. Scopolamine produces rapid antidepressant effects and thus offers the opportunity to characterize potential biomarkers of treatment response within short periods.

Objective  

To determine if baseline brain activity when processing emotional information can predict treatment response to scopolamine in MDD.

Design  

A double-blind, placebo-controlled, crossover study together with repeated functional magnetic resonance imaging, acquired as participants performed face-identity and face-emotion working memory tasks.

Setting  

National Institute of Mental Health Division of Intramural Research Programs.

Participants  

Fifteen currently depressed outpatients meeting DSM-IV criteria for recurrent MDD and 21 healthy participants, between 18 and 55 years of age.

Main Outcome Measure  

The magnitude of treatment response to scopolamine (percentage of change in the Montgomery-Asberg Depression Rating Scale score between study end and baseline) was correlated with blood oxygen level–dependent (BOLD) signal associated with each working memory component (encode, maintenance, and test) for both identity and emotion tasks. Treatment response also was correlated with change in BOLD response (scopolamine vs baseline). Baseline activity was compared between healthy and MDD groups.

Results  

Baseline BOLD response in the bilateral middle occipital cortex, selectively during the stimulus-processing components of the emotion working memory task (no correlation during the identity task), correlated with treatment response magnitude. Change in BOLD response following scopolamine administration in overlapping areas in the middle occipital cortex while performing the same task conditions also correlated with clinical response. Healthy controls showed higher activity in the same visual regions than patients with MDD during baseline.

Conclusion  

These results implicate cholinergic and visual processing dysfunction in the pathophysiology of MDD and suggest that neural response in the visual cortex, selectively to emotional stimuli, may provide a useful biomarker for identifying patients who will respond favorably to scopolamine.