可預測憂鬱治療反應的神經生物標記


  【24drs.com】根據一篇小型、安慰劑控制之影像研究,重度憂鬱異常(MDD)患者腦部中、視覺皮質區域對情緒刺激的神經反應,可能有助於預測靜脈注射scopolamine的治療反應。
  
  研究者發現,在情緒相關操作記憶測試中,重度憂鬱患者的憂鬱症狀有顯著大幅改善者,開始時的雙側枕中皮質的神經活性,較接受scopolamine之後低。
  
  換句話說,在測試中,開始時的腦部訊號與腦部治療反應幅度相關。
  
  開始時,與健康同儕者相比,重度憂鬱患者這些腦部視覺區域的活性顯著較低(認為可能有視覺處理障礙)。
  
  國家心智健康研究中心(NIMH)的Maura L. Furey博士等人寫道,確實有需要改善個別病患目前的治療選項,可辨識治療反應之生物標記有助達到此目標。
  
  研究者指出,該研究顯示,單看腦部功能不足以預測治療反應;換句話說,必須要有操作任務和/或刺激特定的神經活性作為參考。
  
  而這方法是否也可成功地預測其他治療結果,仍是經驗性的問題。
  
  這篇研究線上登載於1月30日的JAMA Psychiatry期刊。
  
  這些研究者在2011年國際躁鬱症研討會發表了一篇研究,一般用來治療暈車(船)的antimuscarinic拮抗劑scopolamine,對躁鬱症憂鬱患者提供了迅速的抗憂鬱效果。
  
  現在,這個快速的效果提供了短期治療反應之潛在生物標記的機會。
  
  目前的研究中,研究者納入了15名成年重度憂鬱門診病患(75%男性;平均年紀32.9歲)與21健康對照組(57%男性;平均年紀30.5歲)。
  
  所有參與者在開始時都接受1次靜脈輸注安慰劑生理食鹽水,之後,分別輸注3次安慰劑、或輸注 3次4.0 μg/kg的scopolamine、或3次活性藥物之後3次安慰劑;各次治療之間間隔3-5天。
  
  參與者也進行了3次功能性磁振造影(fMRI),同時進行面對面的身份確認和面對面情感操作記憶任務。在開始時和輸注2次scopolamine之後進行這些掃描。
  
  每次輸注前和最後一次輸注後3-5天,進行「Montgomery-Asberg Depression Rating Scale (MADRS)」量表評估;治療反應定義為,研究開始到研究結束時的MADRS改變;主要結果測量是治療反應幅度,和開始時的血氧值相關(BOLD)訊號以及操作記憶任務有關;治療的「完全反應」定義為MADRS分數降低50%以上。
  
  結果顯示,重度憂鬱病患的MADRS分數,從開始時到研究結束時平均降低63%。
  
  這些病患的治療反應幅度,和處理情緒相關之操作記憶任務時的視覺皮質BOLD訊號反應有顯著關聯,但是和處理辨識身分的任務無關。
  
  MADRS分數降低較多者,和處理情緒資訊時的這些腦部區域的神經活性較低有關,如同在用藥前的基礎測量時所測的。
  
  此外,與基礎測量相比,接受scopolamine之後,同樣的腦部區域的BOLD反應較高時,則MADRS分數降低幅度較多。若開始時的BOLD反應就比較高,而非接受相關活性治療之後,則MADRS分數降低較少。
  
  研究者寫道,這些結果認為,重度憂鬱的病理生理包括膽鹼和視覺處理障礙,而視覺皮質對情緒刺激的神經反應,可能可以作為辨識哪些病患對scopolamine反應較佳的可用生物標記。
  
  資料來源: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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