可预测忧郁治疗反应的神经生物标记


  【24drs.com】根据一篇小型、安慰剂控制之影像研究,重度忧郁异常(MDD)患者脑部中、视觉皮质区域对情绪刺激的神经反应,可能有助于预测静脉注射scopolamine的治疗反应。
  
  研究者发现,在情绪相关操作记忆测试中,重度忧郁患者的忧郁症状有显著大幅改善者,开始时的双侧枕中皮质的神经活性,较接受scopolamine之后低。
  
  换句话说,在测试中,开始时的脑部讯号与脑部治疗反应幅度相关。
  
  开始时,与健康同侪者相比,重度忧郁患者这些脑部视觉区域的活性显著较低(认为可能有视觉处理障碍)。
  
  国家心智健康研究中心(NIMH)的Maura L. Furey博士等人写道,确实有需要改善个别病患目前的治疗选项,可辨识治疗反应之生物标记有助达到此目标。
  
  研究者指出,该研究显示,单看脑部功能不足以预测治疗反应;换句话说,必须要有操作任务和/或刺激特定的神经活性作为参考。
  
  而这方法是否也可成功地预测其它治疗结果,仍是经验性的问题。
  
  这篇研究在线登载于1月30日的JAMA Psychiatry期刊。
  
  这些研究者在2011年国际躁郁症研讨会发表了一篇研究,一般用来治疗晕车(船)的antimuscarinic拮抗剂scopolamine,对躁郁症忧郁患者提供了迅速的抗忧郁效果。
  
  现在,这个快速的效果提供了短期治疗反应之潜在生物标记的机会。
  
  目前的研究中,研究者纳入了15名成年重度忧郁门诊病患(75%男性;平均年纪32.9岁)与21健康对照组(57%男性;平均年纪30.5岁)。
  
  所有参与者在开始时都接受1次静脉输注安慰剂生理食盐水,之后,分别输注3次安慰剂、或输注 3次4.0 μg/kg的scopolamine、或3次活性药物之后3次安慰剂;各次治疗之间间隔3-5天。
  
  参与者也进行了3次功能性磁振造影(fMRI),同时进行面对面的身份确认和面对面情感操作记忆任务。在开始时和输注2次scopolamine之后进行这些扫描。
  
  每次输注前和最后一次输注后3-5天,进行「Montgomery-Asberg Depression Rating Scale (MADRS)」量表评估;治疗反应定义为,研究开始到研究结束时的MADRS改变;主要结果测量是治疗反应幅度,和开始时的血氧值相关(BOLD)讯号以及操作记忆任务有关;治疗的「完全反应」定义为MADRS分数降低50%以上。
  
  结果显示,重度忧郁病患的MADRS分数,从开始时到研究结束时平均降低63%。
  
  这些病患的治疗反应幅度,和处理情绪相关之操作记忆任务时的视觉皮质BOLD讯号反应有显著关联,但是和处理辨识身分的任务无关。
  
  MADRS分数降低较多者,和处理情绪信息时的这些脑部区域的神经活性较低有关,如同在用药前的基础测量时所测的。
  
  此外,与基础测量相比,接受scopolamine之后,同样的脑部区域的BOLD反应较高时,则MADRS分数降低幅度较多。若开始时的BOLD反应就比较高,而非接受相关活性治疗之后,则MADRS分数降低较少。
  
  研究者写道,这些结果认为,重度忧郁的病理生理包括胆碱和视觉处理障碍,而视觉皮质对情绪刺激的神经反应,可能可以作为辨识哪里些病患对scopolamine反应较佳的可用生物标记。
  
  资料来源:http://www.24drs.com/professional/list/content.asp?x_idno=6981&x_classno=0&x_chkdelpoint=Y
  

Neural Biomarker May Predict Response to Depression Treatment

By Deborah Brauser
Medscape Medical News

A neural response to emotional stimuli in the visual cortex areas of the brain in patients with major depressive disorder (MDD) may help predict treatment response to intravenous scopolamine, according to a small, placebo-controlled imaging study.

Investigators found significantly greater improvements in depressive symptoms for the patients with MDD that, during an emotion-related working memory task, showed lower neural activity in the bilateral middle occipital cortex at baseline compared with after receiving scopolamine.

In other words, the baseline brain signal during the task correlated with treatment response magnitude.

The participants with MDD also had significantly lower activity in these visual brain regions at baseline (suggesting visual processing dysfunction) than did their healthy peers.

"The need to improve current methods of treatment selection for individual patients is clear, and the identification of biomarkers of response has the potential to do so," write Maura L. Furey, PhD, from the National Institute of Mental Health (NIMH) in Bethesda, Maryland, and colleagues.

The investigators note that the study shows that brain function alone is not enough to predict treatment response. Instead, "task- and/or stimulus-specific neural activity is necessary."

"Whether this approach also will successfully predict outcome following other treatments remains an empirical question," they add.

The study was published online January 30 in JAMA Psychiatry.

Rapid Antidepressant Effect

As reported at the time by Medscape Medical News, the investigators presented a study at the 2011 International Conference on Bipolar Disorder showing that the antimuscarinic antagonist scopolamine, which has been commonly used to treat motion sickness, provided a rapid antidepressant effect in patients with bipolar depression.

They now write that this quick effect "offers the opportunity to characterize potential biomarkers of treatment response within short periods."

For the current study, the researchers enrolled 15 adult outpatients diagnosed with MDD (75% men; mean age, 32.9 years) and 21 healthy counterparts (57% men; mean age, 30.5 years).

All participants received in a single session an intravenous infusion of a placebo saline solution at baseline, followed by either 3 sessions of an infusion with the placebo and 3 sessions of an infusion with 4.0 μg/kg of scopolamine or 3 sessions of the active medication then 3 sessions of the placebo. Breaks of 3 to 5 days were scheduled between all treatment sessions.

The participants also underwent 3 sessions of functional magnetic resonance imaging (fMRI) while performing face-identity and face-emotion working memory tasks. These scans occurred at baseline and after 2 of the scopolamine infusions.

The Montgomery-?sberg Depression Rating Scale (MADRS) was administered prior to each infusion and 3 to 5 days after the final infusion.

Treatment response was defined as change from baseline to study end on the MADRS; and the main outcome measure was magnitude of treatment response correlated with a baseline blood oxygen level–dependent (BOLD) signal associated with the working memory tasks.

A "full response" to treatment was defined as a 50% or greater reduction in MADRS score.

Treatment Response

Results showed that the patients with MDD had a mean reduction in MADRS score of 63% from baseline to end of study.

Treatment response magnitude for these patients was significantly correlated with a BOLD signal response in the visual cortex during the working memory task that dealt with emotion, but not the task that dealt with identity.

Larger decreases in MADRS scores were associated with lower neural activity in these brain regions during the processing of emotional information, as measured at the predrug baseline assessment.

In addition, larger reductions in MADRS scores were found when the BOLD response in the same brain region was higher after receiving scopolamine compared with the baseline measurement — whereas a higher BOLD response at baseline rather than after receiving the active treatment correlated with smaller reductions in MADRS scores.

"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," write the investigators.

The study was funded by the NIMH Division of Intramural Research Programs. A full list of financial disclosures can be found in the original article.

JAMA Psychiatry. Published online January 30, 2013. Abstract

    
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