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標題: | 精神分裂症患者代謝異常發展趨勢與增添肌酸對患者的影響 Trend in metabolic abnormality and the effect of creatine augmentation in chronic schizophrenia patients |
作者: | Shuo-Fei Chen 陳碩菲 |
指導教授: | 沈立言 |
關鍵字: | 精神分裂症,肌酸,抗精神病藥物,糖尿病,認知功能,活性與負性症狀量表, schizophrenia,creatine,antipsychotic,impaired fasting glucose,cognitive tests,PANSS, |
出版年 : | 2013 |
學位: | 博士 |
摘要: | 精神分裂症是一種反覆發作且需要長期治療的疾病,臨床上表現為思維、情感、認知功能等多方面障礙以及社交或職業功能退化。許多研究指出精神分裂症患者的代謝異常發生率較高,譬如肥胖、心血管疾病、葡萄糖耐受量異常或是糖尿病比例偏高,並且這些因子會增加病患的醫療風險與社會整體的醫療成本。本研究擬探討,在現有的抗精神病藥物繼續治療的同時,精神分裂症患者活性與負性症狀分數與代謝異常發展趨勢的相關性,以及增添肌酸補充劑對精神分裂症患者的影響,期許了解並找出改善精神分裂症病患的精神與代謝異常發展。在精神分裂症患者代謝異常發展趨勢研究中,追蹤 401 位精神分裂症患者在 2 年期間代謝異常的變化,結果發現病患在罹病治療期間的 BMI、血脂肪與血糖等代謝異常是持續發展;活性與負性症狀量表廣泛被用於評量精神分裂症病人症狀嚴重度,研究假設活性與負性症狀分數可以預測病人未來代謝指數異常發展狀況,統計分析精神分裂症活性負性症狀分數與代謝指數的相關性,精神分裂症的活性與負性症狀總分與身體質量指數(p =0 .045)呈現負相關,負性症狀總分與身體質量指數(p =0 .002)呈現負相關,與高密度脂蛋白(p = 0.004)呈現正相關。精神分裂症的活性症狀與一般精神病理症狀則與任何代謝異常指數無顯著關係。在增添肌酸補充劑對精神分裂症患者的影響採隨機分配、雙盲及安慰劑試驗,將70位參與研究的病人隨機分為安慰劑及肌酸組(每天5克肌酸)。參與增添肌酸補充劑的病人,在加入時血液生化檢驗數據也顯示代謝症候群在精神分裂症族群中佔有很高的比例。經過7天與28天的肌酸增添,肌酸組血清肌酸濃度大約為安慰劑組的2.5~5倍(p < 0.01),尿液肌酸濃度大約為安慰劑組的12~14倍(p < 0.01),但是血液及尿液肌酸酐濃度濃度、蛋白尿、AST、ALT及BUN值二組間無顯著差異,說明研究所增添的肌酸不須經過肝臟代謝為肌酸酐,大部分的肌酸直接以原態由尿液中排出,因此不會造成病人的肝臟與腎臟的傷害。另外,空腹投與安慰劑並不會造成30分鐘後空腹血糖的變化(p =0.9),證明甘露糖醇可用來當作本研究的安慰劑使用。經28天肌酸增添,精神分裂症病人活性與負性症狀量表的總分、活性症狀、負性症狀和一般精神病理症狀在肌酸組有顯著改善(p<0.01),其中又以一般精神病理症狀改善較大,但對總活性症狀差異較小,因此增添肌酸無法有效改善dopamine過度刺激產生幻聽、幻覺及妄想等症狀,推測可能的原因與肌酸可改變大腦能量代謝途徑,活化病人大腦前額葉對葡萄糖新陳代謝率,進而使病人負性症狀得以改善。臨床整體評估分數及簡易智能評估分數肌酸組有顯著差異,但增添肌酸卻對威斯康辛卡片排序測驗卻無顯著影響,威斯康辛卡片排序測驗執行功能就如同病人活性與負性症狀相同是精神分裂症的獨立特質,不會因為精神症狀的緩解或改善而恢復。 Schizophrenia is a mental disorder with repeated psychotic episodes that requires long term treatment. In addition to the psychiatric syndromes, patients are exposed to a higher risk of metabolic syndrome under antipsychotic treatment, and hence causing further physical health problems and increasing the cost of medical services. The aims of my study were to investigate the trend in metabolic abnormality and severity of psychosis syndrome in chronic schizophrenia patients in 2 years follow up period and the effects of creatine augmentation on impaired fasting glucose in schizophrenia patients. In the first study, we examined if baseline psychosis profile may predict the change of a set of metabolic traits among schizophrenia patients exposed to antipsychotics. Contributions of age, gender, type of antipsychositics, body mass index fasting glucose and lipid profiles to Positive and Negative Syndrome Scale in 401 chronic schizophrenia patients were examined by general linear model. When sex interaction was concerned, total score was negatively correlated with BMI (p =0 .045) but there was no correlation with other metabolic traits; negative syndrome was negatively correlated with BMI (p = 0.002) and positively with HDLC (p =0.004). No metabolic traits were correlated with positive syndrome or general psychopathology. We conclude that lower BMI and continuous loss of BMI are capital health problems in schizophrenia patients with severe psychosis syndrome especially the negative syndrome. In the second study, we investigated the effects of oral creatine augmentation on antipsychotics in schizophrenia patients with impaired fasting glucose. Creatine is an amino acid formed from arginine, glycine and methionine. Previous studies have shown that oral augmentation of creatine is effective in improving the psychiatric syndrome of schizophrenia patients and the glucose tolerance of diabetic patients. PANSS, WCST and MMSE are three cognitive tests that are used to measure the effects of oral creatine on psychotic syndrome. We included hospitalization schizophrenia patients and subgrouped them into two groups(placebo and 5g creatine per day). Oral administering period lasted 28 days, and then metabolism syndromes index, blood sugar, kidney index and cognitive tests were analyzed. Our results showed that the serum and urine creatine concentration are significantly increased (p < 0.01), while serum and urine creatinine concentration, AST, ALT and BUN were not significantly increased after 7 days and 28 days oral creatine augmentation. The lack of increase in creatinine output under creatine augmentation was due to the large excess of urine excretion. We demonstrated that oral creatine augmentation did not affect liver and kidney function in schizophrenia patients. In cognitive tests, the total score, G total, N total and P total for PANSS are significantly improved(p<0.01). Creatine failed to improve positive syndrome score due to dopamine over-stimulation, but it improves negative syndrome which may be due to impairment in prefrontal cortex glucose metabolism. In metabolic syndrome index, there were no statistical differences after 28 day creatine augmentation. Our finding support that creatine can improve cognitive syndrome in schizophrenia patients, but further study with larger sample size is warranted. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/17584 |
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