藥物治療失敗的老年憂鬱病患有白質異常


  February 18, 2008 — 根據磁振擴散張量造影(magnetic resonance diffusion tensor imaging)研究,年長憂鬱病患但抗憂鬱藥物失敗者出現白質異常。
  
  神經影像掃描發現,與對抗憂鬱藥物有反應者相比,無反應者在多元額邊腦區域、在新紋狀體、以及皮質下白質區域等處有較低的不等向性因子—或者比較非等方性之水擴散。
  
  文獻發表於2008年2月版的美國精神醫學期刊(American Journal of Psychiatry)。
  
  此研究認為皮質-紋狀體-邊緣網絡之白質異常可視為容易受損,會增加慢性老年憂鬱的可能性,此研究由威爾康奈爾醫學院的George S. Alexopoulos醫師所領導。
  
  編輯評論作者之一、加州大學洛杉磯分校Semel神經科學研究中心的Anand Kumar醫師向Medscape精神病學表示,較低的不等向性可能表示潛在的神經異常—在一些白質神經纖維束可能改變軸索膜和髓磷脂;有這種異常(低的不等向性)的病患,本研究發現其對治療反應較差。
  
  【為什麼有一些病患無法緩解?】
  作者寫道,儘管治療進步,許多憂鬱的年長患者難以有效治療;他們假設,治療失敗之年長憂鬱病患的腦部白質區域有一些微小構造異常,會造成腦化的腦部的再平衡功能減弱。
  
  他們招募了62名60歲以上的非失智、非妄想年長病患,這些人的24題漢氏憂鬱量表(24-item Hamilton Depression Rating (HAM-D) scale)評分在18分以上。
  
  這些人之中,有48人(平均年紀70歲)在2週的安慰劑期之後持續符合症狀規範(HAM-D評分18-34;平均22.2),這些人進入12週的escitalopram藥物治療期,然後接受擴散張量造影。
  
  第12週時,未緩解者(n=23)的皮質-紋狀體-邊緣網絡白質區域比達到緩解者(n=25)有較低的不等向性因子。
  
  研究團隊寫道,我們的發現和觀察研究所提出的一些腦部的構造異常和老年憂鬱有關的論點一致,他們也指出,微小的解剖異常可能會造成一些年長者對抗憂鬱治療產生阻抗性。
  
  【易受影響的病患族群】
  同樣來自Semel神經科學研究中心的編輯Kumar醫師和Olusola Ajilore醫師寫道,這是新的研究發現,代表試圖利用現代科技回答易受影響的病患族群的臨床表現和生物影響等問題。
  
  Kumar醫師表示,擴散張量造影是一種神經影像方式,可以及早辨識對治療有無反應;在精準的發現可以用來治療監控的影像科技之前,需要有更多臨床研究樣本;目前,這些方式是重要的研究工具。
  
  Alexopoulos醫師接受Forest Pharmaceuticals和 Cephalon的研究資金;參與Forest Pharmaceuticals的科學諮詢會;接受Forest、Cephalon、Bristol-Myers Squibb、GlaxoSmithKline、Pfizer、Janssen和 Lilly等之演講贊助;接受Comprehensive Neuroscience之支持而發展老年精神異常治療規範。其他作者的財經宣告列於文獻中。Kumar 和 Ajilore醫師兩位編輯宣稱無相關資金往來。

Depressed Geriatric Patients W

By Marlene Busko
Medscape Medical News

February 18, 2008 — Depressed elderly patients who failed to achieve remission with antidepressant therapy had white matter abnormalities, according to a magnetic resonance diffusion tensor imaging study.

Neuroimaging scans revealed that, compared with patients who responded to antidepressant treatment, nonresponders had lower fractional anisotropy — or more ordered (anisotropic) diffusion of water — in multiple frontal limbic brain areas, in the neostriatum, and in subcortical white matter regions.

The article is published in the February 2008 issue of the American Journal of Psychiatry.

This study suggests that white matter abnormalities in cortico-striato-limbic networks confer vulnerability, which increases the likelihood of chronic geriatric depression, the group, led by George S. Alexopoulos, MD, at Weill Cornell Medical College, in White Plains, New York, write.

"Lower anisotropy probably reflects an underlying neurobiological abnormality — possibly changes in the axonal membrane and myelin — in certain white matter tracts; patients with this abnormality, of which lower anisotropy is a marker, responded poorly to treatment in this study," Anand Kumar, MD, from the Semel Institute for Neuroscience at the University of California, Los Angeles, and coauthor of an accompanying editorial, told Medscape Psychiatry.

Why Do Some Patients Fail to Remit?

Despite treatment advances, many depressed older adults fail to achieve remission, the researchers write. They hypothesized that depressed elderly people who failed to achieve remission had microstructural abnormalities in their brain's white matter that would compromise the aging brain's ability to re-equilibrate itself.

They enrolled 62 nondemented, nondelusional elderly individuals age 60 years and older who had a score of 18 or greater on the 24-item Hamilton Depression Rating (HAM-D) scale.

Of these, 48 individuals (mean age, 70) continued to meet symptom criteria (HAM-D score, 18 to 34; mean, 22.2) after a 2-week placebo phase. These subjects entered a 12-week phase of escitalopram treatment and then underwent diffusion tensor imaging.

At 12 weeks, those who did not achieve remission (n = 23) had lower fractional anisotropy in several cortico-striato-limbic white matter areas than those who achieved remission (n = 25).

"Our findings are consistent with observations suggesting that some structural brain abnormalities are associated with poor outcomes in late-life depression," the team writes, adding that microanatomical abnormalities might predispose certain elderly people to be resistant to antidepressant therapy.

Vulnerable Patient Population

"The finding is novel and represents an attempt to utilize modern technology to answer both clinically relevant and biologically significant questions in a vulnerable patient population," editorialists Dr. Kumar and Olusola Ajilore, MD, also from the Semel Institute for Neuroscience, write.

Diffusion tensor imaging is a neuroimaging approach that has the potential to identify early responders/nonresponders to treatment, Dr. Kumar said, cautioning that definitive studies using large clinical samples are needed before the precise relevance of neuroimaging techniques to treatment monitoring can be determined. Currently, these approaches are important research tools, he noted.

Dr. Alexopoulos has received research grant funding from Forest Pharmaceuticals and Cephalon; has participated in scientific advisory board meetings for Forest Pharmaceuticals; has given lectures supported by Forest, Cephalon, Bristol-Myers Squibb, GlaxoSmithKline, Pfizer, Janssen, and Lilly; and has received support from Comprehensive Neuroscience for development of treatment guidelines in late-life psychiatric disorders. The financial disclosures of the other authors are listed in the article. The editorialists, Drs. Kumar and Ajilore, have disclosed no relevant financial relationships.

Am J Psychiatry. 2008; 165:238-244. Abstract

    
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nOPARlY8E
2016/1/13
  Sunsripirgly well-written and ...
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