注意力不足過動症的病理生理學
關於注意力不足過動症的病理生理學,截至西元2019年7月底,注意力不足過動症(ADHD)被認為是肇因於部分腦內的神經傳導物質系統的損傷(特別是與多巴胺和正腎上腺素有關的神經傳導系統),進而對患者的腦部執行功能產生不良的影響。[1][2]多巴胺與正腎上腺素的腦內神經通道大多起源自腦內的腹側被蓋區和藍斑核,並由此投射至不同的腦區且管理許多認知的流程(與認知功能相關的處理流程)。[1][3]特別是那些投射至前額葉和紋狀體的腦內多巴胺通道和腦內正腎上腺素通道/藍斑核系統。它們主要的工作就是負責調節執行功能(認知和行為的功能與管理)、動機、 酬賞/報償的感受能力、和運動神經的功能[註 1]。[1][2][3]以上是目前已知在注意力不足過動症的病理生理學中扮演主要腳色的幾條腦內神經通道。也已經有人提議強化對於注意力不足過動症更全面的概觀以及更多可能與之相關的腦內神經通道之探究。[2][5][6]
![](http://upload.wikimedia.org/wikipedia/commons/thumb/6/64/Synapse_dopaminergique.png/220px-Synapse_dopaminergique.png)
大腦結構
編輯在兒童注意力不足過動症患者中,普遍存有一些腦部結構(特別是左側的前額葉、後頂葉皮質)在體積上小於平均值的現象。[2][7]其他諸如注意力不足過動症患者的:前額 - 紋狀體-小腦和前額葉-紋狀體-丘腦迴路也被發現與非注意力不足過動症患者不同。[2][5][6]
ADHD兒童的雙側額葉、頂葉和顳葉灰質體積小於同樣正在發育中的非ADHD兒童,ADHD兒童的腦部構造跟對照組(同樣正在發育中的非ADHD兒童)相比後,體積差異最大的部分是右額葉和左顳葉。進一步檢視實驗組(ADHD兒童)與對照組(非ADHD兒童)的額葉子區域後發現,實驗組與對照組彼此之間的左側眶額葉皮質、左側初級運動皮層(M1)、和左側運動輔助區(SMC)體積差異最大。[8] 與「特定亞區(左前額葉、左前葉、左額葉、M1和右SMC)相關的ADHD關聯程度」跟「ADHD症狀的嚴重程度」成反比,舉例來說:當前述皮層的體積越小則「過動—衝動」症狀的嚴重程度越高,前述皮層的體積與「過動—衝動」症狀的嚴重程度成反比。[8]ADHD個案組在伏隔核、海馬迴、杏仁核、基底核、顱內等區域之體積皆有較健康控制組(非ADHD兒童)更小的體積;實驗組(ADHD兒童)與對照組(非ADHD兒童)在蒼白球與丘腦的體積相比之下則沒有在統計學上達到顯著差異。進一步分析發現,在大部分區域(包括杏仁核、基底核、伏隔核、海馬迴),小於15歲的ADHD孩童與健康發展孩童(非ADHD兒童)的腦體積差異程度,較持續到成人的ADHD患者(大於21歲)與健康受試成人(非ADHD成人)的比較差異程度來得大,這暗示著ADHD患者之大腦發展遲緩的現象。[9]
另外,目前學術界對於ADHD藥物治療是否會對於ADHD患者的大腦內部結構體積產生改變,出現了不一致的研究結果。[9]
研究發現,ADHD青少年患者腦中的白質路徑(white matter tracts)存在不對稱的情況,這可能表示患者腦中各腦區的整合於連動發展出現不一致的問題,這樣的問題或許與ADHD患者的行為模式相關聯。[10]
神經傳導物質的通道/路徑
編輯目前的研究模型包含了 中腦皮質素-多巴胺通道 及藍斑核-去甲腎上腺素系統。[1][2][3]用於治療注意力不足過動症的中樞神經刺激劑,其療效可能是起因於它增進了神經傳導物質在這些系統中的活動。[2][3][11]注意力不足過動症患者腦部中的 5-羥色胺能(與血清素有關)通道、 穀氨酸能(一種神經傳導物質)通道、 或膽鹼能通道可能也存有一些導致注意力不足過動症症狀的原因。[11][12][13]
另有研究發現,注意力不足過動症是由一種發生於腦前額葉的遺傳性的多巴胺新陳代謝失常有關[14][15][16]。更近期的研究認為正腎上腺素的新陳代謝亦會對病情有所影響[16]。
利用核磁共振成像技術(MRI)對腦部掃描的研究顯示患有ADHD和非ADHD的孩子的圖象有分別。不少科學家認為這足以證明ADHD是和腦部創傷有關。但腦部影像只說明了作為腦內燃料的葡萄糖的分佈。在成人ADHD患者的腦掃描中,控制專注力的部份由於葡萄糖水平較低,所以顯得不太活躍。不過,沒有證據顯示低葡萄糖水平與注意力缺陷有關聯,亦無法推論兩者之間的因果關係。[17]
執行功能和動機
編輯注意力不足過動症的症狀起因於某些執行功能上的缺陷,例如:注意力/專注力的控制、衝動-過動控制、及工作記憶。[19][2][3][20]執行功能簡單來說就是一整群包含認知處理過程的集合[a]。而這集合必須能夠成功的幫助一個人選擇並督促自己做出得以實現他那經過深思熟慮過後的目標之行為。[19][3][20]執行功能也幫助一個人能適當的應對新奇、複雜、全面、或模稜兩可的情況[21][22]。
注意力不足過動症患者先天的執行功能損傷造成以下這些症狀:難以維持有規劃的、難以有組織性的、缺乏時間觀念、過度的拖延、難以保持專注、難以把注意力放對地方、難以忽略與任務不相干的外務/誘惑、有情緒管理的困難、難以把細節記起來。[19][2][3]注意力不足過動症患者在長期記憶的表現可看出注意力不足過動症患者的長期記憶是沒有損傷的。注意力不足過動症患者在提取長期記憶時所產生的困難顯然是肇因於工作記憶[b]的受損[19][23]。 端視一個注意力不足過動症患者其腦部發展的程度與其所在環境對其執行功能要求的程度的比例,因此有些注意力不足過動症患者可能直到青少年時期甚至是成年期(特別是成年初期)才開始顯露出注意力不足過動症的症狀。[19][24][25][26]
注意力不足過動症與患者在兒童青少年乃至成年時期缺乏動機相關。兒童青少年甚至成人注意力不足過動症患者會發現自己比起眼前立即的回饋、酬賞、或滿足,更難以專注在長遠的目標、回報、回饋、酬賞、或滿足,並展現出對於眼前立即的回饋、酬賞、或滿足的衝動言行。[27]
註釋
編輯備註
編輯參見
編輯文獻來源
編輯- ^ 1.0 1.1 1.2 1.3 1.4 Chandler DJ, Waterhouse BD, Gao WJ. New perspectives on catecholaminergic regulation of executive circuits: evidence for independent modulation of prefrontal functions by midbrain dopaminergic and noradrenergic neurons. Front. Neural Circuits. 2014-05, 8: 53. PMC 4033238 . PMID 24904299. doi:10.3389/fncir.2014.00053.
- ^ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 Malenka RC, Nestler EJ, Hyman SE. Chapters 10 and 13. Sydor A, Brown RY (編). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience 2nd. New York: McGraw-Hill Medical. 2009: 266, 315, 318–323. ISBN 9780071481274.
Early results with structural MRI show thinning of the cerebral cortex in ADHD subjects compared with age-matched controls in prefrontal cortex and posterior parietal cortex, areas involved in working memory and attention.
- ^ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 Malenka RC, Nestler EJ, Hyman SE. Chapter 6: Widely Projecting Systems: Monoamines, Acetylcholine, and Orexin. Sydor A, Brown RY (編). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience 2nd. New York: McGraw-Hill Medical. 2009: 148, 154–157. ISBN 9780071481274.
NOTE: DA: dopamine, LC: locus coeruleus, VTA: ventral tegmental area, 5HT: serotonin (5-hydroxytryptamine) - ^ 高淑芬. 找回專注力:成人ADHD全方位自助手冊. 博客來. 2016-05-09 [2018-09-03]. (原始內容存檔於2016-11-30) (中文).
- ^ 5.0 5.1 Castellanos FX, Proal E. Large-scale brain systems in ADHD: beyond the prefrontal-striatal model. Trends Cogn. Sci. (Regul. Ed.). 2012-01, 16 (1): 17–26. PMC 3272832 . PMID 22169776. doi:10.1016/j.tics.2011.11.007.
Recent conceptualizations of ADHD have taken seriously the distributed nature of neuronal processing [10,11,35,36]. Most of the candidate networks have focused on prefrontal-striatal-cerebellar circuits, although other posterior regions are also being proposed [10].
- ^ 6.0 6.1 Cortese S, Kelly C, Chabernaud C, Proal E, Di Martino A, Milham MP, Castellanos FX. Toward systems neuroscience of ADHD: a meta-analysis of 55 fMRI studies. Am J Psychiatry. 2012-10, 169 (10): 1038–1055. PMC 3879048 . PMID 22983386. doi:10.1176/appi.ajp.2012.11101521.
- ^ 7.0 7.1 Krain AL, Castellanos FX. Brain development and ADHD. Clin Psychol Rev. 2006-08, 26 (4): 433–444. PMID 16480802. doi:10.1016/j.cpr.2006.01.005.
- ^ 8.0 8.1 Jacobson, Lisa A.; Crocetti, Deana; Dirlikov, Benjamin; Slifer, Keith; Denckla, Martha Bridge; Mostofsky, Stewart H.; Mahone, E. Mark. Anomalous Brain Development Is Evident in Preschoolers With Attention-Deficit/Hyperactivity Disorder. Journal of the International Neuropsychological Society : JINS (Cambridge University Press (CUP)). 2018-03-26, 24 (6): 531–539. ISSN 1355-6177. PMC 6035105 . PMID 29576028. doi:10.1017/s1355617718000103.
- ^ 9.0 9.1 Hoogman, Martine; Bralten, Janita; Hibar, Derrek P; Mennes, Maarten; Zwiers, Marcel P; Schweren, Lizanne S J. Subcortical brain volume differences in participants with attention deficit hyperactivity disorder in children and adults: a cross-sectional mega-analysis. The lancet. Psychiatry (Elsevier BV). 2017, 4 (4): 310–319. ISSN 2215-0366. PMC 5933934 . PMID 28219628. doi:10.1016/s2215-0366(17)30049-4.
- ^ Douglas. Hemispheric brain asymmetry differences in youths with attention-deficit/hyperactivity disorder. NeuroImage: Clinical. 2018, 18: 744–752. PMC 5988460 . PMID 29876263. doi:10.1016/j.nicl.2018.02.020.
- ^ 11.0 11.1 Bidwell LC, McClernon FJ, Kollins SH. Cognitive enhancers for the treatment of ADHD. Pharmacol. Biochem. Behav. 2011-08, 99 (2): 262–274. PMC 3353150 . PMID 21596055. doi:10.1016/j.pbb.2011.05.002.
- ^ Cortese S. The neurobiology and genetics of Attention-Deficit/Hyperactivity Disorder (ADHD): what every clinician should know. Eur. J. Paediatr. Neurol. 2012-09, 16 (5): 422–433. PMID 22306277. doi:10.1016/j.ejpn.2012.01.009.
- ^ Lesch KP, Merker S, Reif A, Novak M. Dances with black widow spiders: dysregulation of glutamate signalling enters centre stage in ADHD. Eur Neuropsychopharmacol. 2013-06, 23 (6): 479–491. PMID 22939004. doi:10.1016/j.euroneuro.2012.07.013.
- ^ Dresel, S; Krause, J; Krause, KH; LaFougere, C; Brinkbäumer, K; Kung, HF; Hahn, K; Tatsch, K. Attention deficit hyperactivity disorder: binding of [99mTc]TRODAT-1 to the dopamine transporter before and after methylphenidate treatment.. European journal of nuclear medicine. 2000, 27 (10): 1518–24. ISSN 0340-6997. PMID 11083541.
- ^ Krause, KH; Dresel, SH; Krause, J; la Fougere, C; Ackenheil, M. The dopamine transporter and neuroimaging in attention deficit hyperactivity disorder.. Neuroscience and biobehavioral reviews. 2003, 27 (7): 605–13. ISSN 0149-7634. PMID 14624805.
- ^ 16.0 16.1 Bymaster, F. Atomoxetine Increases Extracellular Levels of Norepinephrine and Dopamine in Prefrontal Cortex of Rat A Potential Mechanism for Efficacy in Attention Deficit/Hyperactivity Disorder. Neuropsychopharmacology (Springer Nature). 2002, 27 (5): 699–711 [2017-02-17]. doi:10.1016/s0893-133x(02)00346-9.
The selective norepinephrine (NE) transporter inhibitor atomoxetine (formerly called tomoxetine or LY139603) has been shown to alleviate symptoms in Attention Deficit/Hyperactivity Disorder (ADHD).
- ^ 17.0 17.1 Cerebral Glucose Metabolism in Adults with Hyperactivity of Childhood Onset 互聯網檔案館的存檔,存檔日期2017-08-02.: Zametkin AJ, Nordahl TE, Gross M, King AC, Semple WE, Rumsey J, Hamburger S, Cohen RM. (1990) Cerebral glucose metabolism in adults with hyperactivity of childhood onset. New England Journal of Medicine 1990; 323(20): 1361-1366. November 15, 1990 doi:10.1056/NEJM199011153232001 Author address: Section on Clinical Brain Imaging, National Institute of Mental Health, NIH, Bethesda, MD 20892.
- ^ Russell Barkley. Barkley Deficits in Executive Functioning Scale. UpToDate. [2018-02-24]. (原始內容存檔於2018-02-27).
- ^ 19.0 19.1 19.2 19.3 19.4 Brown TE. ADD/ADHD and Impaired Executive Function in Clinical Practice. Curr Psychiatry Rep. 2008-10, 10 (5): 407–411. PMID 18803914. doi:10.1007/s11920-008-0065-7.
- ^ 20.0 20.1 Diamond A. Executive functions. Annu. Rev. Psychol. 2013, 64: 135–168. PMC 4084861 . PMID 23020641. doi:10.1146/annurev-psych-113011-143750.
- ^ Executive Function: Development, Individual Differences, and Clinical Insights. ScienceDirect: 429. 2013-01-01 [2018-09-19]. doi:10.1016/B978-0-12-397267-5.00062-5. (原始內容存檔於2020-10-19).
Executive function (EF) is an umbrella term that encompasses the set of higher-order processes (such as inhibitory control, working memory, and attentional flexibility) that govern goal-directed action and adaptive responses to novel, complex, or ambiguous situations (Hughes et al., 2005).
- ^ Nigg, Joel T. Annual Research Review: On the relations among self-regulation, self-control, executive functioning, effortful control, cognitive control, impulsivity, risk-taking, and inhibition for developmental psychopathology. Journal of child psychology and psychiatry, and allied disciplines (Wiley). 2017, 58 (4): 361–383. ISSN 0021-9630. PMC 5367959 . PMID 28035675. doi:10.1111/jcpp.12675.
- ^ Skodzik T, Holling H, Pedersen A. Long-Term Memory Performance in Adult ADHD: A Meta-Analysis. J. Atten. Disord. 2013-11. PMID 24232170. doi:10.1177/1087054713510561.
- ^ 陳錦宏. 心動家族:注意力不足過動症ADHD的第三條路. 台灣心動家族兒童青少年關懷協會. Tc-adhd.com. 2016-12-13 [2017-02]. (原始內容存檔於2018-02-24) (中文(臺灣)).
- ^ Attention deficit hyperactivity disorder in adults: Epidemiology, pathogenesis, clinical features, course, assessment, and diagnosis. UpToDate. 2016-11-03 [2017-10-29]. (原始內容存檔於2017-10-30).
Some adults present with impairment in a clinical setting only later in life when they confront new and increasingly complex tasks that characterize adulthood and that cannot be managed with their existing neuropsychological repertoire.
- ^ Canela, Carlos; Buadze, Anna; Dube, Anish; Eich, Dominique; Liebrenz, Michael. Chao, Linda , 編. Skills and compensation strategies in adult ADHD – A qualitative study. PloS one (Public Library of Science (PLoS)). 2017-09-27, 12 (9): e0184964. ISSN 1932-6203. PMC 5617155 . PMID 28953946. doi:10.1371/journal.pone.0184964.
- ^ Modesto-Lowe V, Chaplin M, Soovajian V, Meyer A. Are motivation deficits underestimated in patients with ADHD? A review of the literature. Postgrad Med. 2013, 125 (4): 47–52. PMID 23933893. doi:10.3810/pgm.2013.07.2677.
Previous studies suggest that a clinical approach using interventions to improve motivational processes in patients with ADHD may improve outcomes as children with ADHD transition into adolescence and adulthood.