臺灣博碩士論文加值系統

強迫症(Obsessive-compulsive disorder, OCD)一般開始於兒童和青少年，盛行率估計約為2.5％，與憂鬱症、物質濫用疾患都是常見的精神科疾病。青少年時期以男性發生高於女性，約2比1，平均發病年齡約為20歲，但在成年後男性與女性發生的比例約為1比1。嚴重強迫症病人會耗費許多時間、精力，其社會職業功能被嚴重影響，60~80％的患者併發重鬱症。藥物和認知行為治療仍然為主要治療方式可以減緩症狀。然而患者25-40％的病人治療效果不好。「腦深層電刺激術」（Deep brain stimulation, DBS）現已擴展至治療神經精神疾病，目前小規模的人體實驗針對強迫症治療的結果認為有些正面療效，論文是以台灣首次「腦深層電刺激術於頑固型強迫症治療」(IRB094-33)的人體試驗的結果呈現與討論。論文的第一章簡介強迫症與神經外科手術，第二章實驗進行手術後DBS急性測試病人反應，並且評估15月後的治療效果。論文的第三章部分實驗評估長期三年認知功能的變化與強迫症的關聯性。第四章部份更進一步腦深層刺激術於頑固型強迫症治療之五年長期追蹤。第五章是總結，我們認為「腦深層電刺激術」應用於頑固型強迫症有一定療效，未來更進一步的研究必須評估不同的參數和可能的預測因子。

Obsessive-compulsive disorder (OCD) is a common mental illness, usually begins in children and adolescents. The prevalence is about 2.5%. OCD, depression, and substance abuse disorders are common psychiatric disorders. Adolescence in males than females, about 2 to 1, with an average age of onset is about 20 years old, but the proportion of men and women in adulthood occurs about 1 to 1. Patients with severe OCD will spend a lot of time, and energy. Social and professional functions are severely affected. 60 to 80 percent of patients also have major depressive disorder . Medication and cognitive behavioral therapy remains the main treatment. However, 25-40 % of patients have poor outcomes. Deep brain stimulation (DBS) has been extended to the treatment of neurological and psychiatric disorders. The current small-scale human trials have some positive effects. In this thesis, we introduced OCD and related neurosurgery. We studied the acute and long-term DBS in patients with refractory OCD after IRB approved. Our results show that DBS has a certain effect on the treatment-resistant OCD. Future research will need to evaluate different parameters and possible predictors.

目錄
中文摘 ---------------------------------------------------------------------------------------- 4
英文摘要 ------------------------------------------------------------------------------------- 5
第一章 文獻回顧
前言------------------------------------------------------------------------------ 6
第一節 腦部體積的研究--------------------------------------------------- 8
第二節 腦部代謝研究----------------------------------------------------- 8
第三節 強迫症的基因 ---------------------------------------------------- 9
第四節 強迫症的腦部迴路 --------------------------------------------- 10
第五節 強迫症的手術治療 --------------------------------------------- 11
第六節 強迫症的腦深層電刺激術------------------------------------- 13
第二章 腦深層電刺激(腹側內囊/腹側紋狀體)於頑固型強迫症患者-術後急性電刺激雙盲試驗以及15月治療評估
中文摘要 --------------------------------------------------------------------- 16
英文摘要 --------------------------------------------------------------------- 18
背景說明 --------------------------------------------------------------------- 20
材料及方法 ------------------------------------------------------------------ 21
實驗結果 --------------------------------------------------------------------- 24
討論 --------------------------------------------------------------------------- 29
第三章 頑固型強迫症患者接受長期腦深層電刺激對於認知功能的影響
中文摘要 --------------------------------------------------------------------- 32
英文摘要 --------------------------------------------------------------------- 33
背景說明 --------------------------------------------------------------------- 35
材料及方法 ------------------------------------------------------------------ 36
實驗結果 --------------------------------------------------------------------- 37
討論 --------------------------------------------------------------------------- 40
第四章 腦深層刺激術於頑固型強迫症治療五年長期追蹤
中文摘要 --------------------------------------------------------------------- 42
英文摘要 --------------------------------------------------------------------- 43
背景說明 --------------------------------------------------------------------- 45
材料及方法 ------------------------------------------------------------------ 46
實驗結果 --------------------------------------------------------------------- 46
討論 --------------------------------------------------------------------------- 52
第五章 總結及展望
參 考 文 獻 ------------------------------------------------------------------------------- 59
附錄 ------------------------------------------------------------------------------------------ 65

ABELSON, J. F., KWAN, K. Y., O'ROAK, B. J., BAEK, D. Y., STILLMAN, A. A., MORGAN, T. M., MATHEWS, C. A., PAULS, D. L., RASIN, M. R., GUNEL, M., DAVIS, N. R., ERCAN-SENCICEK, A. G., GUEZ, D. H., SPERTUS, J. A., LECKMAN, J. F., DURE, L. S. T., KURLAN, R., SINGER, H. S., GILBERT, D. L., FARHI, A., LOUVI, A., LIFTON, R. P., SESTAN, N. & STATE, M. W. (2005a). Sequence variants in SLITRK1 are associated with Tourette's syndrome. Science, 310, 317-320.
ABELSON, J. L., CURTIS, G. C., SAGHER, O., ALBUCHER, R. C., HARRIGAN, M., TAYLOR, S. F., MARTIS, B. & GIORDANI, B. (2005b). Deep brain stimulation for refractory obsessive-compulsive disorder. Biol Psychiatry, 57, 510-516.
ALEXANDER, G. E., DELONG, M. R. & STRICK, P. L. (1986). Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci, 9, 357-381.
AOUIZERATE, B., CUNY, E., MARTIN-GUEHL, C., GUEHL, D., AMIEVA, H., BENAZZOUZ, A., FABRIGOULE, C., ALLARD, M., ROUGIER, A., BIOULAC, B., TIGNOL, J. & BURBAUD, P. (2004). Deep brain stimulation of the ventral caudate nucleus in the treatment of obsessive-compulsive disorder and major depression. Case report. J Neurosurg, 101, 682-686.
AYLWARD, E. H., HARRIS, G. J., HOEHN-SARIC, R., BARTA, P. E., MACHLIN, S. R. & PEARLSON, G. D. (1996). Normal caudate nucleus in obsessive-compulsive disorder assessed by quantitative neuroimaging. Arch Gen Psychiatry, 53, 577-584.
BALDO, B. A. & KELLEY, A. E. (2007). Discrete neurochemical coding of distinguishable motivational processes: insights from nucleus accumbens control of feeding. Psychopharmacology (Berl), 191, 439-459.
BALLANTINE, H. T., JR., CASSIDY, W. L., FLANAGAN, N. B. & MARINO, R., JR. (1967). Stereotaxic anterior cingulotomy for neuropsychiatric illness and intractable pain. J Neurosurg, 26, 488-495.
BAXTER, L. R. (1990). Brain imaging as a tool in establishing a theory of brain pathology in obsessive compulsive disorder. J Clin Psychiatry, 51 Suppl, 22-25; discussion 26.
BLACK, S. E. (2012). Brain stimulation, learning, and memory. N Engl J Med, 366, 563-565.
CHANG, C. H., CHEN, S. Y., HSIAO, Y. L., CHEN, S. J., TSAI, S. T., CHANG, C. H., YEH, Y. Y. & TSAI, H. C. (2009). Hypomania-like syndrome induced by deep brain stimulation of bilateral anterior limbs of the internal capsules. Prog Neuropsychopharmacol Biol Psychiatry, 33, 906-907.
CHANG, C. H., CHEN, S. Y., HSIAO, Y. L., TSAI, S. T. & TSAI, H. C. (2010). Hypomania with hypersexuality following bilateral anterior limb stimulation in obsessive-compulsive disorder. J Neurosurg, 112, 1299-1300.
DENYS, D., MANTIONE, M., FIGEE, M., VAN DEN MUNCKHOF, P., KOERSELMAN, F., WESTENBERG, H., BOSCH, A. & SCHUURMAN, R. (2010). Deep brain stimulation of the nucleus accumbens for treatment-refractory obsessive-compulsive disorder. Arch Gen Psychiatry, 67, 1061-1068.
DOSTROVSKY, J. O. & LOZANO, A. M. (2002). Mechanisms of deep brain stimulation. Mov Disord, 17 Suppl 3, S63-68.
EICHELE, H. & PLESSEN, K. J. (2013). Neural plasticity in functional and anatomical MRI studies of children with Tourette syndrome. Behav Neurol, 27, 33-45.
FALOWSKI, S. M., SHARAN, A., REYES, B. A., SIKKEMA, C., SZOT, P. & VAN BOCKSTAELE, E. J. (2011). An evaluation of neuroplasticity and behavior after deep brain stimulation of the nucleus accumbens in an animal model of depression. Neurosurgery, 69, 1281-1290.
FERRAO, Y. A., SHAVITT, R. G., BEDIN, N. R., DE MATHIS, M. E., CARLOS LOPES, A., FONTENELLE, L. F., TORRES, A. R. & MIGUEL, E. C. (2006). Clinical features associated to refractory obsessive-compulsive disorder. J Affect Disord, 94, 199-209.
FRANZINI, A., FERROLI, P., LEONE, M. & BROGGI, G. (2003). Stimulation of the posterior hypothalamus for treatment of chronic intractable cluster headaches: first reported series. Neurosurgery, 52, 1095-1099; discussion 1099-1101.
GABRIELS, L., COSYNS, P., NUTTIN, B., DEMEULEMEESTER, H. & GYBELS, J. (2003). Deep brain stimulation for treatment-refractory obsessive-compulsive disorder: psychopathological and neuropsychological outcome in three cases. Acta Psychiatr Scand, 107, 275-282.
GOODMAN, W. K., FOOTE, K. D., GREENBERG, B. D., RICCIUTI, N., BAUER, R., WARD, H., SHAPIRA, N. A., WU, S. S., HILL, C. L., RASMUSSEN, S. A. & OKUN, M. S. (2010)Deep Brain Stimulation for Intractable Obsessive Compulsive Disorder: Pilot Study Using a Blinded, Staggered-Onset Design. Biol Psychiatry, 67, 535-542.
GRADOS, M. A., RIDDLE, M. A., SAMUELS, J. F., LIANG, K. Y., HOEHN-SARIC, R., BIENVENU, O. J., WALKUP, J. T., SONG, D. & NESTADT, G. (2001). The familial phenotype of obsessive-compulsive disorder in relation to tic disorders: the Hopkins OCD family study. Biol Psychiatry, 50, 559-565.
GRANT, J. E., ODLAUG, B. L. & CHAMBERLAIN, S. R. (2011). Neurocognitive response to deep brain stimulation for obsessive-compulsive disorder: a case report. Am J Psychiatry, 168, 1338-1339.
GREENBERG, B. D., GABRIELS, L. A., MALONE, D. A., JR., REZAI, A. R., FRIEHS, G. M., OKUN, M. S., SHAPIRA, N. A., FOOTE, K. D., COSYNS, P. R., KUBU, C. S., MALLOY, P. F., SALLOWAY, S. P., GIFTAKIS, J. E., RISE, M. T., MACHADO, A. G., BAKER, K. B., STYPULKOWSKI, P. H., GOODMAN, W. K., RASMUSSEN, S. A. & NUTTIN, B. J. (2010). Deep brain stimulation of the ventral internal capsule/ventral striatum for obsessive-compulsive disorder: worldwide experience. Mol Psychiatry, 15, 64-79.
GREENBERG, B. D., MALONE, D. A., FRIEHS, G. M., REZAI, A. R., KUBU, C. S., MALLOY, P. F., SALLOWAY, S. P., OKUN, M. S., GOODMAN, W. K. & RASMUSSEN, S. A. (2006). Three-year outcomes in deep brain stimulation for highly resistant obsessive-compulsive disorder. Neuropsychopharmacology, 31, 2384-2393.
HAQ, I. U., FOOTE, K. D., GOODMAN, W. G., WU, S. S., SUDHYADHOM, A., RICCIUTI, N., SIDDIQUI, M. S., BOWERS, D., JACOBSON, C. E., WARD, H. & OKUN, M. S. (2011). Smile and laughter induction and intraoperative predictors of response to deep brain stimulation for obsessive-compulsive disorder. Neuroimage, 54 Suppl 1, S247-255.
HETTEMA, J. M., NEALE, M. C. & KENDLER, K. S. (2001). A review and meta-analysis of the genetic epidemiology of anxiety disorders. Am J Psychiatry, 158, 1568-1578.
HUFF, W., LENARTZ, D., SCHORMANN, M., LEE, S. H., KUHN, J., KOULOUSAKIS, A., MAI, J., DAUMANN, J., MAAROUF, M., KLOSTERKOTTER, J. & STURM, V. Unilateral deep brain stimulation of the nucleus accumbens in patients with treatment-resistant obsessive-compulsive disorder: Outcomes after one year. Clin Neurol Neurosurg, 112, 137-143.
JIMENEZ-PONCE, F., VELASCO-CAMPOS, F., CASTRO-FARFAN, G., NICOLINI, H., VELASCO, A. L., SALIN-PASCUAL, R., TREJO, D. & CRIALES, J. L. (2009). Preliminary study in patients with obsessive-compulsive disorder treated with electrical stimulation in the inferior thalamic peduncle. Neurosurgery, 65, 203-209; discussion 209.
KAWAKAMI, K., TAKAI-KAWAKAMI, K., TOMONAGA, M., SUZUKI, J., KUSAKA, T. & OKAI, T. (2006). Origins of smile and laughter: a preliminary study. Early Hum Dev, 82, 61-66.
KOPELL, B. H., GREENBERG, B. & REZAI, A. R. (2004). Deep brain stimulation for psychiatric disorders. J Clin Neurophysiol, 21, 51-67.
KOPELL, B. H. & GREENBERG, B. D. (2008). Anatomy and physiology of the basal ganglia: implications for DBS in psychiatry. Neurosci Biobehav Rev, 32, 408-422.
KUBU CS, G. B., MALONE D, RASMUSSEN S, FRIEHS G, MACHADO A, ET AL. (2008). Cognitive effects of DBS in the ventral striatum in patients with severe major
depression and obsessive compulsive disorder. Biol Psychiatry 49, 232.
KUHN, J., GRUNDLER, T. O., LENARTZ, D., STURM, V., KLOSTERKOTTER, J. & HUFF, W. (2010). Deep brain stimulation for psychiatric disorders. Dtsch Arztebl Int, 107, 105-113.
LAKHAN, S. E. & CALLAWAY, E. (2010). Deep brain stimulation for obsessive-compulsive disorder and treatment-resistant depression: systematic review. BMC Res Notes, 3, 60.
LECKMAN, J. F. & CHITTENDEN, E. H. (1990). Gilles de La Tourette's syndrome and some forms of obsessive-compulsive disorder may share a common genetic diathesis. Encephale, 16 Spec No, 321-323.
LIPSMAN, N., NEIMAT, J. S. & LOZANO, A. M. (2007). Deep brain stimulation for treatment-refractory obsessive-compulsive disorder: the search for a valid target. Neurosurgery, 61, 1-11; discussion 11-13.
LOPES, A. C., DE MATHIS, M. E., CANTERAS, M. M., SALVAJOLI, J. V., DEL PORTO, J. A. & MIGUEL, E. C. (2004). [Update on neurosurgical treatment for obsessive compulsive disorder]. Rev Bras Psiquiatr, 26, 62-66.
MALLET, L., POLOSAN, M., JAAFARI, N., BAUP, N., WELTER, M. L., FONTAINE, D., DU MONTCEL, S. T., YELNIK, J., CHEREAU, I., ARBUS, C., RAOUL, S., AOUIZERATE, B., DAMIER, P., CHABARDES, S., CZERNECKI, V., ARDOUIN, C., KREBS, M. O., BARDINET, E., CHAYNES, P., BURBAUD, P., CORNU, P., DEROST, P., BOUGEROL, T., BATAILLE, B., MATTEI, V., DORMONT, D., DEVAUX, B., VERIN, M., HOUETO, J. L., POLLAK, P., BENABID, A. L., AGID, Y., KRACK, P., MILLET, B. & PELISSOLO, A. (2008). Subthalamic nucleus stimulation in severe obsessive-compulsive disorder. N Engl J Med, 359, 2121-2134.
MCKAY, D., ABRAMOWITZ, J. S., CALAMARI, J. E., KYRIOS, M., RADOMSKY, A., SOOKMAN, D., TAYLOR, S. & WILHELM, S. (2004). A critical evaluation of obsessive-compulsive disorder subtypes: symptoms versus mechanisms. Clin Psychol Rev, 24, 283-313.
NORDAHL, T. E., BENKELFAT, C., SEMPLE, W. E., GROSS, M., KING, A. C. & COHEN, R. M. (1989). Cerebral glucose metabolic rates in obsessive compulsive disorder. Neuropsychopharmacology, 2, 23-28.
NUTTIN, B. J., GABRIELS, L. A., COSYNS, P. R., MEYERSON, B. A., ANDREEWITCH, S., SUNAERT, S. G., MAES, A. F., DUPONT, P. J., GYBELS, J. M., GIELEN, F. & DEMEULEMEESTER, H. G. (2003). Long-term electrical capsular stimulation in patients with obsessive-compulsive disorder. Neurosurgery, 52, 1263-1272; discussion 1272-1264.
OKUN, M. S., BOWERS, D., SPRINGER, U., SHAPIRA, N. A., MALONE, D., REZAI, A. R., NUTTIN, B., HEILMAN, K. M., MORECRAFT, R. J., RASMUSSEN, S. A., GREENBERG, B. D., FOOTE, K. D. & GOODMAN, W. K. (2004). What's in a "smile?" Intra-operative observations of contralateral smiles induced by deep brain stimulation. Neurocase, 10, 271-279.
PALLANTI, S., HOLLANDER, E., BIENSTOCK, C., KORAN, L., LECKMAN, J., MARAZZITI, D., PATO, M., STEIN, D., ZOHAR, J. & INTERNATIONAL TREATMENT REFRACTORY, O. C. D. C. (2002). Treatment non-response in OCD: methodological issues and operational definitions. Int J Neuropsychopharmacol, 5, 181-191.
PAULS, D. L. & LECKMAN, J. F. (1986). The inheritance of Gilles de la Tourette's syndrome and associated behaviors. Evidence for autosomal dominant transmission. N Engl J Med, 315, 993-997.
ROBINSON, D., WU, H., MUNNE, R. A., ASHTARI, M., ALVIR, J. M., LERNER, G., KOREEN, A., COLE, K. & BOGERTS, B. (1995). Reduced caudate nucleus volume in obsessive-compulsive disorder. Arch Gen Psychiatry, 52, 393-398.
SCARONE, S., COLOMBO, C., LIVIAN, S., ABBRUZZESE, M., RONCHI, P., LOCATELLI, M., SCOTTI, G. & SMERALDI, E. (1992). Increased right caudate nucleus size in obsessive-compulsive disorder: detection with magnetic resonance imaging. Psychiatry Res, 45, 115-121.
SCHOBER, J. M. & PFAFF, D. (2007). The neurophysiology of sexual arousal. Best Pract Res Clin Endocrinol Metab, 21, 445-461.
SCHOENEN, J., DI CLEMENTE, L., VANDENHEEDE, M., FUMAL, A., DE PASQUA, V., MOUCHAMPS, M., REMACLE, J. M. & DE NOORDHOUT, A. M. (2005). Hypothalamic stimulation in chronic cluster headache: a pilot study of efficacy and mode of action. Brain, 128, 940-947.
SCHRUERS, K., KONING, K., LUERMANS, J., HAACK, M. J. & GRIEZ, E. (2005). Obsessive-compulsive disorder: a critical review of therapeutic perspectives. Acta Psychiatr Scand, 111, 261-271.
SHAH, D. B., PESIRIDOU, A., BALTUCH, G. H., MALONE, D. A. & O'REARDON, J. P. (2008). Functional neurosurgery in the treatment of severe obsessive compulsive disorder and major depression: overview of disease circuits and therapeutic targeting for the clinician. Psychiatry (Edgmont), 5, 24-33.
SHAPIRA, N. A., OKUN, M. S., WINT, D., FOOTE, K. D., BYARS, J. A., BOWERS, D., SPRINGER, U. S., LANG, P. J., GREENBERG, B. D., HABER, S. N. & GOODMAN, W. K. (2006). Panic and fear induced by deep brain stimulation. J Neurol Neurosurg Psychiatry, 77, 410-412.
SPRINGER, U. S., BOWERS, D., GOODMAN, W. K., SHAPIRA, N. A., FOOTE, K. D. & OKUN, M. S. (2006). Long-term habituation of the smile response with deep brain stimulation. Neurocase, 12, 191-196.
STEIN, D. J. (2002). Obsessive-compulsive disorder. Lancet, 360, 397-405.
SZESZKO, P. R., ROBINSON, D., ALVIR, J. M., BILDER, R. M., LENCZ, T., ASHTARI, M., WU, H. & BOGERTS, B. (1999). Orbital frontal and amygdala volume reductions in obsessive-compulsive disorder. Arch Gen Psychiatry, 56, 913-919.
TSAI, H. C., CHEN, S. Y., TSAI, S. T., HUNG, H. Y. & CHANG, C. H. (2010). Hypomania following bilateral ventral capsule stimulation in a patient with refractory obsessive-compulsive disorder. Biol Psychiatry, 68, e7-8.
TYE, S. J., FRYE, M. A. & LEE, K. H. (2009). Disrupting disordered neurocircuitry: treating refractory psychiatric illness with neuromodulation. Mayo Clin Proc, 84, 522-532.
VIGNERI, S., GUARALDI, P., CALANDRA-BUONAURA, G., TERLIZZI, R., CECERE, A., BARLETTA, G. & CORTELLI, P. (2012). Switching on the deep brain stimulation: effects on cardiovascular regulation and respiration. Auton Neurosci, 166, 81-84.
WALKUP, J. T., LABUDA, M. C., SINGER, H. S., BROWN, J., RIDDLE, M. A. & HURKO, O. (1996). Family study and segregation analysis of Tourette syndrome: evidence for a mixed model of inheritance. Am J Hum Genet, 59, 684-693.