透過您的圖書館登入
IP:18.117.104.53
  • 學位論文

老年重鬱症之腦部質子磁振造影頻譜研究

Brain Proton Magnetic Resonance Spectroscopy Study of Late-life Major Depressive Disorder

指導教授 : 劉金昌

摘要


老年憂鬱症患者腦部異常的特徵主要是大腦萎縮與缺血性的病變,尤其在frontal-striatal迴路與海馬迴。患者的認知功能障礙並不會隨著憂鬱症狀緩解而改善,持續的認知功能障礙可能是發展成失智症的危險因子。近年來腦影像技術有快速的進步,其中proton magnetic resonance spectroscopy (1H MRS)是magnetic resonance imaging (MRI)的進一步技術,可以在in vivo的情況下測量大腦中具有氫原子,且有足夠濃度的一些生化物質的濃度,包括N-acetyl-L-aspartate (NAA)、total creatine/phosphocreatine (tCr)、choline-containing compounds (choline)、以及myo-inositol。本研究的研究目的為1)以大腦1H MRS來探討老年憂鬱症患者在重鬱期的大腦生化物質濃度的特徵;2)探討在緩解期的老年憂鬱症患者的大腦1H MRS生化物質濃度的特徵,並且探討這些特徵是否與緩解期的認知功能障礙相關。 本研究採用個案對照設計。有兩個研究樣本,第一個樣本的研究對象為27名符合DSM-IV重鬱期的重鬱症的老年人與19名對照組;第二部分為130名處於緩解期的重鬱症老年人與100名對照組老人。邀請個案進行MRI與1H MRS檢查,第一部分全部加入完成1H MRS,第二部分則有96位個案組與60位對照組完成。第二部分進行完整的認知功能評估,並依照mild cognitive impairment (MCI)的診斷,分類為no MCI、amnestic MCI (aMCI)與non-amnestic MCI (naMCI)。 研究結果顯示,未使用藥物的重鬱期病患在額葉的NAA/tCr低於對照組,在基底核的choline/tCr與myo-inositol/tCr則是高於對照組,MMSE總分則與基底核的myo-inositol/tCr呈現負相關。緩解期的重鬱症個案有52.3%符合MCI,其中28.5%為aMCI,23.8%為naMCI。緩解期的重鬱症在基底核NAA下降、choline與myo-inositol上升,在額葉則是NAA下降與myo-inositol上升,在海馬迴有比較高的myo-inositol。aMCI組的MRI則有明顯的側腦室擴大,在海馬迴的myo-inositol則高於對照組;naMCI在基底核的NAA濃度低於對照組,myo-inositol高於對照組,在額葉的NAA濃度明顯低於對照組。 重鬱期的老年憂鬱症患者,在額葉可能有神經退化的病程進行中,而皮質下的基底核,則可能顯示細胞周轉增加、glia cell功能變異與訊息傳導的異常。大腦的變化持續地出現在緩解期,除了重鬱期的變化外,緩解期的額葉myo-inositol升高,基底核的NAA有降低的現象。aMCI則是有側腦室擴大且特別與海馬迴的myo-inositol的增加相關,間接支持重鬱症的aMCI亞型可能是阿茲海默症的前驅表現;而naMCI主要的位置則是額葉與基底核,特徵為NAA下降與myo-inositol的增加,顯示這兩個位置在naMCI不只有神經元損失,也有glia cell功能或是訊息傳導異常的現象。本研究的結論為老年重鬱症無論在重鬱期或緩解期都有大腦功能的變化,frontostriatal circuit與海馬迴都是受影響的位置。緩解期的重鬱症老年人也有高的比例有認知障礙,不同亞型的MCI在frontostriatal circuit與海馬迴有不同的1H MRS特徵,也代表不同亞型的MCI有不同的病理機轉。

並列摘要


Brain features of late-life major depressive disorder are atrophy and ischemic change, particularly in the frontostriatal circuit and hippocampus. Patients with late-life depression may present various patterns of cognitive impairment which may persist even after successful antidepressant treatment. Proton magnetic resonance spectroscopy (1H MRS) is a newly magnetic resonance imaging (MRI) technique and is widely used to detect certain biochemicals, including N-acetyl-L-aspartate (NAA)、total creatine/phosphocreatine (tCr)、choline-containing compounds (choline)、and myo-inositol。 The aims of this study were 1) to investigate the 1H MRS features of late-life major depressive disorder at the depressive state;2) to investigate the 1H MRS features of late-life major depressive disorder in remission, and illustrate their association with cognitive impairments. Case-control study designs were adopted. There were two study samples for the study. The first one recruited 27 elders with major depressive disorder and 19 comparisons. The second one were 130 elders with major depressive disorder in remission and 100 comparisons. All study participants of the first part completed MRI and 1H MRS, while 96 cases and 60 comparisons of the second part did. Comprehensive neuropsychological tests were administrated and diagnostic criteria of mild cognitive impairment (MCI) were used to subtype those cases into no MCI, amnestic MCI (aMCI), and non-amnestic MCI (naMCI). Unmedicated patients with late-life major depressive disorder had a significantly lower NAA/tCr in the frontal lobe, and higher choline/tCr and myo-inositol/tCr in the basal ganglia than the comparisons. The myo-inositol/tCr correlated with global cognitive function among the patients. Among the remitted patients, 52.3% met the definition of MCI, including 28.5% with aMCI and 23.8% with naMCI. Even in remission, the patients showed lower NAA and higher choline and myo-inositol in the basal ganglia, lower NAA and higher myo-inositol in the frontal lobe, and higher myo-inositol in the hippocampus. Subtype of aMCI was associated with ventricular atrophy and higher myo-inositol in the hippocampus, while naMCI was associated with lower NAA in the basal ganglia and frontal lobe and higher myo-inositol in the basal ganglia. Brain abnormality persists after remission of depressive symptoms. The brain characteristics of subtype of aMCI were suggested the prodromal of dementia. The main change of naMCI located at frontal lobe and basal ganglia. In conclusion, brain biochemical changes of the elders with major depressive disorder at both depressive and remitted states. High rate of MCI occurred in the late-life major depressive disorders even in remission. Different subtypes of MCI related to late-life major depressive disorder presented different pathophysiological change in the frontostriatal circuit and hippocampus.

參考文獻


1. Chong MY, Tsang HY, Chen CS, Tang TC, Chen CC, Yeh TL, Lee YH, Lo HY: Community study of depression in old age in Taiwan: prevalence, life events and socio-demographic correlates. Br J Psychiatry 2001, 178(1):29-35.
2. Chen CS, Chong MY, Tsang HY: Clinically significant non-major depression in a community-dwelling elderly population: epidemiological findings. Int J Geriatr Psychiatry 2007, 22(6):557-562.
3. Murray CJ, Lopez AD: Alternative projections of mortality and disability by cause 1990-2020: Global Burden of Disease Study. Lancet 1997, 349(9064):1498-1504.
4. Krishnan KR: Neuroanatomic substrates of depression in the elderly. J Geriatr Psychiatry Neurol 1993, 6(1):39-58.
5. Kumar A, Bilker W, Jin Z, Udupa J: Atrophy and high intensity lesions: complementary neurobiological mechanisms in late-life major depression. Neuropsychopharmacology 2000, 22(3):264-274.

延伸閱讀