B族维生素对卒中后抑郁干预作用的临床研究
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摘要
目前对缺血性卒中的防治进行了许多研究,其中绝大多数对于干预效果的关注焦点集中在卒中的复发或躯体功能障碍的严重程度上,而对于干预对卒中后认知功能状态和精神心理状态的影响研究不多。抑郁障碍是缺血性脑损害或局灶性脑血管病变的直接后果,卒中后功能障碍越重抑郁障碍的可能性越大,抑郁障碍直接影响脑血管病的发生、发展和患者功能康复。近年来,高同型半胱氨酸血症(hyper-homocysteinemia, Hey)作为一个脑血管性病变的高危因素受到关注。Hcy与CVD存在着密切关系,目前大量的研究工作己证实Hcy是导致CVD发生的独立危险因素。脑卒中后发生PSD临床较多见。本研究旨在探讨B族维生素是否降低Hhcy对缺血性脑卒引发的卒中后抑郁(Post Stroke Depression,PSD)有防治作用。
目的本研究对缺血性卒中患者Hhcy进行干预,目的在于评价卒中后不同时间患者卒中后抑郁与血浆Hcy水平的关系,从而了解降低血浆Hcy水平是否有助于缺血性卒中患者卒中后抑郁的改善。
方法
1.采用前瞻性、平行开放对照试验方法,对2006年8月至2007年10月期间来源于天津市第三中心医院神经内科住院或门急诊就诊的新发(病程=1周)脑梗死1000例患者进行了为期2年的观察。
2.将1000例Hhcy脑梗死患者根据年龄、性别及影响卒中的主要危险因素匹配分成干预组(treatment group, T组)和对照组(control group, C组1,每组各500例。干预组患者在常规二级预防基础上加用复合B族维生素。对照组仅采用除B族维生素外的常规治疗,两组患者平行定期随访观察。
3.记录患者入组时、干预后3个月、12个月和24个月的空腹血浆tHcy水平并于患者入组时、干预后1/2个月、3个月、6个月、12个月、18个月和24个月分别采用HAMD评分评估卒中后抑郁的发生情况;HAMD>7分病例为可能有抑郁,HAMD=24分病例为严重抑郁。
结果
1.干预组与对照组基线时血浆tHcy水平差异无统计学意义(p>0.05)。
2.复合B族维生素干预3个月后,干预组血浆tHcy,与对照组比较差异有统计学意义(p<0.05),干预至24个月时,干预组血浆tHcy水平,与对照组比较差异有统计学意义(p<0.05)。
3.两组基线时HAMD评分干预组和对照组,差异无统计学意义(p>0.05)。
4.随访1/2个月、3个月、6个月时干预组与对照组HAMD评分两组间差异均无统计学意义(p>0.05)。随访12个月、18个月、24个月时,干预组HAMD评分低于对照组,两组间差异有统计学意义(p<0.05)。干预组患者随访全程中曾出现过HAMD>7分的发生率,两组间差异无统计学意义(p>0.05)。干预组患者随访24个月时HAMD>7分的发生率,两组间比较差异无统计学意义(p>0.05)。随访6个月时干预组新发HAMD>7分病例,两组间差异无统计学意义(p<0.05);余各随访时间点两组间差异均无统计学意义(p>0.05)。随访3个月、12个月、18个月时干预组HAMD>7分病例的发生低于对照组,两组间比较差异有统计学意义(p<0.05)；其余随访时间点两组HAMD>7分病例的发生组间比较差异均无统计学意义(p>0.05)。随访3个月时干预组严重抑郁病例(HAMD=24分)的发生率高于对照组,两组间比较差异有统计学意义(p<0.05);其余随访时间点两组严重抑郁病(?)(?)(HAMD=24分)的发生率组间比较差异均无统计学意义(p>0.05)。结论患者复合B族维生素干预3个月后,干预组血浆tHcy水平较基线时下降2.88μmol/L,下降幅度为14.7%,与对照组比较差异有统计学意义,干预12个月至24个月时,干预组血浆tHcy水平有进一步下降趋势。提示对Hhcy的脑卒中患者进行复合B族维生素干预,在用药后3个月即可显著降低血浆tHcy水平,而且复合B族维生素在2年以内能够持续有效地控制血浆tHcy水平。患者的卒中后抑郁情况以HAMD评分评价,随访12-24个月时,干预组HA评分低于对照组,两组间差异有统计学意义。随访全程中和随访终末时HAMD>7的患者例数两组间比较差异均无统计学意义。提示复合B族维生素干预在有效降低Hhcy的脑卒中患者血浆tHcy水平的基础上,可能有助于减轻脑卒中后1至2年的抑郁程度,但对抑郁的发生并无影响。
Objectives This study to ischemic stroke patients with Hhcy intervene, aimed at assessing different time after stroke patients with depression and plasma after stroke Hcy level relations, so as to understand the lowering of plasma Hcy level are beneficial to ischemic stroke patients after stroke depression improved.
Methods
1.Adopt forward-looking and parallel controlled trials method of open in August 2006-2007 October period from tianjin of hospital of the 3rd center nerve medicine hospital or clinic of this new hair more than 1 week (course) cerebral infarction 1,000 patients for 2 years of observation.
2.1000 cases of patients with cerebral infarction Hhcy according to age, gender and affecting stroke risk factors of matching into interention group (treatment group, and group T) and the control group (control group, the group C), each group every 500 cases. Intervention group in patients with secondary prevention based on conventional add a composite B vitamins. The control group only used except B vitamins outside the routine therapy, two groups of patients with parallel regular follow-up.
3.Record patients into group, intervention after 3 months,12 and 24 months fasting plasma tHcy level and in patients into group, intervention after 1/2 months,3 months, 6 months,12 months,18 months and twenty-four months respectively by means HAMD score evaluation of depression after stroke occur, depression in decline. HAMD> 7 points for may have depression cases, HAMD> 24 points cases of severe depression in.
Results
1.Intervention ergometry baseline plasma tHcy level, difference was statistically significant (p> 0.05).
2.Composite B vitamins intervention after 3 months, the intervention group plasma tHcy, compared with controls difference was statistically significant (p< 0.05). Intervention to 24 months, intervention group plasma levels for tHcy, compared with controls difference was statistically significant (p< 0.05).
3.Two groups at baseline HAMD score intervention group and measured group no statistically significant difference (p> 0.05).
4.Follow-up 1/2 months,3 months and 6 months intervention ergometry HAMD score difference between the two groups were not statistically significant (p> 0.05). Follow-up of 12 months,18 months,24 months, intervention group HAMD score below the control group, the difference between the two groups was statistically significant (p< 0.05). Patients were followed up for the whole of intervention group appeared in the incidence of HAMD> 7 points, the difference between the two groups was statistically significant (p> 0.05). Intervention group patients were followed up for 24 months and the incidence of HAMD> 7 points, comparative differences between the two groups was statistically significant (p> 0.05). Follow-up of 6 months intervention group new hair HAMD> 7 points cases, the difference between the two groups have statistically significant (p< 0.05). Over the follow-up time point difference between the two groups were not statistically significant (p> 0.05). Follow-up of 3 months,12 months,18 months intervention group HAMD> 7 points cases occur lower than those of the control group, compared between the two groups was statistically significant difference (p< 0.05). The remaining follow-up time point two groups HAMD> 7 points cases occur between groups comparative differences are not statistically significant (p> 0.05). Follow-up of 3 months intervention group severe depression cases (HAMD=24score) incidence, than in control group, comparative differences between the two groups was statistically significant (p< 0.05). The remaining follow-up time point two groups of severe depression cases (HAMD=24score) the incidence of comparative differences between groups were not statistically significant (p> 0.05).
Conclusions Composite B vitamins intervention after 3 months, the intervention group tHcy level is relatively baseline plasma dropped, compared with controls, the difference was statistically significant intervention 12 to 24 months, intervention group plasma tHcy level has further decline. Clew to Hhcy of patients with cerebral apoplexy composite B vitamins intervention, in 3 months after drug can significantly reduced plasma tHcy levels and composite B vitamins within two years, can continue to effectively control plasma tHcy level. Patients with depression after stroke HAMD score index, follow-up of 12-24 months, intervention group HAMD score below the control group, the difference between the two groups was statistically significant. Follow-up the whole and the time of the latest follow-up HAMD> 7 patients,it difference were compared between the two groups was statistically significant. Clew composite B vitamins intervention in effectively reduce the Hhcy in patients with cerebral apoplexy plasma tHcy level of basic, may help to alleviate after stroke 1 to 2 years, but levels of depression on depression occurs and without influence.
目的本研究对缺血性卒中患者Hhcy进行干预,目的在于评价卒中后不同时间患者卒中后抑郁与血浆Hcy水平的关系,从而了解降低血浆Hcy水平是否有助于缺血性卒中患者卒中后抑郁的改善。
方法
1.采用前瞻性、平行开放对照试验方法,对2006年8月至2007年10月期间来源于天津市第三中心医院神经内科住院或门急诊就诊的新发(病程=1周)脑梗死1000例患者进行了为期2年的观察。
2.将1000例Hhcy脑梗死患者根据年龄、性别及影响卒中的主要危险因素匹配分成干预组(treatment group, T组)和对照组(control group, C组1,每组各500例。干预组患者在常规二级预防基础上加用复合B族维生素。对照组仅采用除B族维生素外的常规治疗,两组患者平行定期随访观察。
3.记录患者入组时、干预后3个月、12个月和24个月的空腹血浆tHcy水平并于患者入组时、干预后1/2个月、3个月、6个月、12个月、18个月和24个月分别采用HAMD评分评估卒中后抑郁的发生情况;HAMD>7分病例为可能有抑郁,HAMD=24分病例为严重抑郁。
结果
1.干预组与对照组基线时血浆tHcy水平差异无统计学意义(p>0.05)。
2.复合B族维生素干预3个月后,干预组血浆tHcy,与对照组比较差异有统计学意义(p<0.05),干预至24个月时,干预组血浆tHcy水平,与对照组比较差异有统计学意义(p<0.05)。
3.两组基线时HAMD评分干预组和对照组,差异无统计学意义(p>0.05)。
4.随访1/2个月、3个月、6个月时干预组与对照组HAMD评分两组间差异均无统计学意义(p>0.05)。随访12个月、18个月、24个月时,干预组HAMD评分低于对照组,两组间差异有统计学意义(p<0.05)。干预组患者随访全程中曾出现过HAMD>7分的发生率,两组间差异无统计学意义(p>0.05)。干预组患者随访24个月时HAMD>7分的发生率,两组间比较差异无统计学意义(p>0.05)。随访6个月时干预组新发HAMD>7分病例,两组间差异无统计学意义(p<0.05);余各随访时间点两组间差异均无统计学意义(p>0.05)。随访3个月、12个月、18个月时干预组HAMD>7分病例的发生低于对照组,两组间比较差异有统计学意义(p<0.05)；其余随访时间点两组HAMD>7分病例的发生组间比较差异均无统计学意义(p>0.05)。随访3个月时干预组严重抑郁病例(HAMD=24分)的发生率高于对照组,两组间比较差异有统计学意义(p<0.05);其余随访时间点两组严重抑郁病(?)(?)(HAMD=24分)的发生率组间比较差异均无统计学意义(p>0.05)。结论患者复合B族维生素干预3个月后,干预组血浆tHcy水平较基线时下降2.88μmol/L,下降幅度为14.7%,与对照组比较差异有统计学意义,干预12个月至24个月时,干预组血浆tHcy水平有进一步下降趋势。提示对Hhcy的脑卒中患者进行复合B族维生素干预,在用药后3个月即可显著降低血浆tHcy水平,而且复合B族维生素在2年以内能够持续有效地控制血浆tHcy水平。患者的卒中后抑郁情况以HAMD评分评价,随访12-24个月时,干预组HA评分低于对照组,两组间差异有统计学意义。随访全程中和随访终末时HAMD>7的患者例数两组间比较差异均无统计学意义。提示复合B族维生素干预在有效降低Hhcy的脑卒中患者血浆tHcy水平的基础上,可能有助于减轻脑卒中后1至2年的抑郁程度,但对抑郁的发生并无影响。
Objectives This study to ischemic stroke patients with Hhcy intervene, aimed at assessing different time after stroke patients with depression and plasma after stroke Hcy level relations, so as to understand the lowering of plasma Hcy level are beneficial to ischemic stroke patients after stroke depression improved.
Methods
1.Adopt forward-looking and parallel controlled trials method of open in August 2006-2007 October period from tianjin of hospital of the 3rd center nerve medicine hospital or clinic of this new hair more than 1 week (course) cerebral infarction 1,000 patients for 2 years of observation.
2.1000 cases of patients with cerebral infarction Hhcy according to age, gender and affecting stroke risk factors of matching into interention group (treatment group, and group T) and the control group (control group, the group C), each group every 500 cases. Intervention group in patients with secondary prevention based on conventional add a composite B vitamins. The control group only used except B vitamins outside the routine therapy, two groups of patients with parallel regular follow-up.
3.Record patients into group, intervention after 3 months,12 and 24 months fasting plasma tHcy level and in patients into group, intervention after 1/2 months,3 months, 6 months,12 months,18 months and twenty-four months respectively by means HAMD score evaluation of depression after stroke occur, depression in decline. HAMD> 7 points for may have depression cases, HAMD> 24 points cases of severe depression in.
Results
1.Intervention ergometry baseline plasma tHcy level, difference was statistically significant (p> 0.05).
2.Composite B vitamins intervention after 3 months, the intervention group plasma tHcy, compared with controls difference was statistically significant (p< 0.05). Intervention to 24 months, intervention group plasma levels for tHcy, compared with controls difference was statistically significant (p< 0.05).
3.Two groups at baseline HAMD score intervention group and measured group no statistically significant difference (p> 0.05).
4.Follow-up 1/2 months,3 months and 6 months intervention ergometry HAMD score difference between the two groups were not statistically significant (p> 0.05). Follow-up of 12 months,18 months,24 months, intervention group HAMD score below the control group, the difference between the two groups was statistically significant (p< 0.05). Patients were followed up for the whole of intervention group appeared in the incidence of HAMD> 7 points, the difference between the two groups was statistically significant (p> 0.05). Intervention group patients were followed up for 24 months and the incidence of HAMD> 7 points, comparative differences between the two groups was statistically significant (p> 0.05). Follow-up of 6 months intervention group new hair HAMD> 7 points cases, the difference between the two groups have statistically significant (p< 0.05). Over the follow-up time point difference between the two groups were not statistically significant (p> 0.05). Follow-up of 3 months,12 months,18 months intervention group HAMD> 7 points cases occur lower than those of the control group, compared between the two groups was statistically significant difference (p< 0.05). The remaining follow-up time point two groups HAMD> 7 points cases occur between groups comparative differences are not statistically significant (p> 0.05). Follow-up of 3 months intervention group severe depression cases (HAMD=24score) incidence, than in control group, comparative differences between the two groups was statistically significant (p< 0.05). The remaining follow-up time point two groups of severe depression cases (HAMD=24score) the incidence of comparative differences between groups were not statistically significant (p> 0.05).
Conclusions Composite B vitamins intervention after 3 months, the intervention group tHcy level is relatively baseline plasma dropped, compared with controls, the difference was statistically significant intervention 12 to 24 months, intervention group plasma tHcy level has further decline. Clew to Hhcy of patients with cerebral apoplexy composite B vitamins intervention, in 3 months after drug can significantly reduced plasma tHcy levels and composite B vitamins within two years, can continue to effectively control plasma tHcy level. Patients with depression after stroke HAMD score index, follow-up of 12-24 months, intervention group HAMD score below the control group, the difference between the two groups was statistically significant. Follow-up the whole and the time of the latest follow-up HAMD> 7 patients,it difference were compared between the two groups was statistically significant. Clew composite B vitamins intervention in effectively reduce the Hhcy in patients with cerebral apoplexy plasma tHcy level of basic, may help to alleviate after stroke 1 to 2 years, but levels of depression on depression occurs and without influence.
引文
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[35]Whyte EM, Mulsant BH. Post stroke depression:epidemiology, pathophysiology, and biological treatment. Biol Psychiatry,2002,52(3):253-264.
[36]Verdelho A, Henon H, Lebert F, et al. Depressive symptoms after stroke and relationship with dementia: A three-year follow-up study. Neurology,2004, 62(6):905-911.
[37]Andersen G. Post-stroke depression:Diagnosis and incidence. Eur Psychiatry, 1997,12:255s-260s.
[38]Kauhanen M, Korpelainen JT, Hiltunen P, et al. Poststroke depression correlates with cognitive impairment and neurological deficits. Stroke,1999, 30(9):1875-1880.
[39]龙洁,刘永珍,蔡焯基,等.卒中后抑郁状态的发生率及相关因素研究.中华神经科杂志,2001,34(3)：145-148.
[40]Robinson RG, Bloom FE. Pharmacological treatment following experimental cerebral infarction:implications for understanding psychological symptoms of human stroke. Biol Psychiatry,1977,12(5):669-680.
[41]Navines R, Martin-Santos R, Gomez-Gil E, et al. Effects of citalopram treatment on hypothermic and hormonal responses to the 5-HT1 A receptor agonist buspirone in patients with major depression and therapeutic response. Psychoneuroendocrinology,2007,32(4):411-416.
[42]Reding M, Orto L, Willensky P, et al. The dexamethasone suppression test. An indicator of depression in stroke but not a predictor of rehabilitation outcome. ArchNeurol,1985,42(3):209-212.
[43]Hackett ML, Anderson CS. Predictors of depression after stroke:a systematic review of observational studies. Stroke,2005,36(10):2296-2301.
[44]Reutens S, Sachdev P. Homocysteine in neuropsychiatric disorders of the elderly. Int J Geriatr Psychiatry,2002,17(9):859-864.
[45]Bottiglieri T, Laundy M, Crellin R, et al. Homocysteine, folate, methylation, and monoamine metabolism in depression. J Neurol Neurosurg Psychiatry, 2000,69(2):228-232.
[46]Tiemeier H, van Tuijl HR, Hofman A, et al. Vitamin B12, folate, and homocysteine in depression:the Rotterdam Study. Am J Psychiatry,2002, 159(12):2099-2101.
[47]Dimopoulos N, Piperi C, Salonicioti A, et al. Correlation of folate, vitamin B12 and homocysteine plasma levels with depression in an elderly Greek population. Clin Biochem,2007,40(9-10):604-608.
[48]Sachdev PS, Parslow RA, Lux O, et al. Relationship of homocysteine, folic acid and vitamin B12 with depression in a middle-aged community sample. Psychol Med,2005,35(4):529-538.
[49]Tolmunen T, Hintikka J, Voutilainen S, et al. Association between depressive symptoms and serum concentrations of homocysteine in men:a population study.
[50]Dimopoulos N, Piperi C, Salonicioti A, et al. Correlation of folate, vitamin B12 and homocysteine plasma levels with depression in an elderly Greek population. Clin Biochem,2007,40(9-10):604-608.
[51]Tolmunen T, Hintikka J, Voutilainen S, et al. Association between depressive symptoms and serum concentrations of homocysteine in men:a population study. Am J Clin Nutr,2004,80(6):1574-1578.
[52]Wesson VA, Levitt AJ, Joffe RT. Change in folate status with antidepressant treatment. Psychiatry Res,1994,53(3):313-322.
[53]Miller AL. The methylation, neurotransmitter, and antioxidant connections
[54]Almeida OP, McCaul K, Hankey GJ, et al. Homocysteine and depression in later life. Arch Gen Psychiatry,2008,65(11):1286-1294.
[55]袁勇贵,李海林,吴瑞枝,等.血浆同型半胱氨酸水平及N5,N10一亚甲四氢叶酸还原酶基因多态性与老年期抑郁症的关联研究.中华精神科杂志,2005,38(3)：150-153.
[1]杨玲俐,张志甜卒中后抑郁的流行病学及临床特点,中国卒中杂志,2007,2：907—10.
[2]why EM, Muleant DH.post stroke depression:epidemiology, Pathophysiology, andbidogicaltreatment Biol Psychiatry,2002,52:253-264.
[3]Pohjasvaara, LeppavuoriA, siira I, et al.Frequency and clinical determinants of Poststroke depression.Stroke,1998,29:2311—2317.
[4]Sharpe M, Hawton K, House A, et al.Mood discorders in longterm survivors of stroke:associations with brain lesion ainlesion location andvolume.Psychol Med,1990,20:815-828.
[5]paul SL, DeweyHM, Sturm JW, etal.AG,Prevalence of depression and use of antidepressant medication at 5-years poststroke in the North East Melbourns Stroke Incidence Study.Stroke,2006,37:2854-2855.
[6]Hackett ML, Yapa C, parag V, et al. Frequency of Depression after slroke:a systematic review of observational studies.Stroke,2005,36:1330-1340.
[7]许贤豪主编.神经心理量表检测指南.北京：中国仂协和医科大学出版社,2007.
[8]Frick B, Schrocksnadel K, Neurauter G, et al. Rap id measurement of total plasma homocysteine by HPLC. Clin Chim Acta,2003,331:19-23.
[9]Krijt J, Vackova M, Kozich V. Measurement of homocysteine and other aminothiols in plasma:advantages of using tris (2-carboxetlhyl) phosphine as reductant compared with tri-n-butyphosphine. Clin Chem,2001,47:1821-1828.
[10]Hankey GJ, Jamrozik K, Broadhurst RJ, et al. Long-term risk of first recurrent stroke in the Perth Community Stroke Study. Stroke,1998,29(12):2491-2500.
[11]Homocysteine Studies Collaboration. Homocysteine and risk of ischemic heart disease and stroke:a meta-analysis. JAMA,2002,288(16):2015-2022.
[12]Nygard O, Nordrehaug JE, Refsum H, et al. Plasma homocysteine levels and mortality in patients with coronary artery disease. N Engl J Med,1997, 337(4):230-236.
[13]Brattstrom LE, Hardebo JE, Hultberg BL. Moderate homocysteinemia--a possible risk factor for arteriosclerotic cerebrovascular disease. Stroke,1984, 15(6):1012-1016.
[14]Brattstrom L, Lindgren A, Israelsson B, et al. Hyperhomocysteinaemia in stroke: prevalence, cause, and relationships to type of stroke and stroke risk factors. Eur J Clin Invest,1992,22(3):214-221.
[15]Coull BM, Malinow MR, Beamer N, et al. Elevated plasma homocyst(e)ine concentration as a possible independent risk factor for stroke. Stroke,1990, 21(4):572-576.
[16]Perry IJ, Refsum H, Morris RW, et al. Prospective study of serum total homocysteine concentration and risk of stroke in middle-aged British men. Lancet,1995,346(8987):1395-1398.
[17]Yoo JH, Chung CS, Kang SS. Relation of plasma homocyst(e)ine to cerebral infarction and cerebral atherosclerosis. Stroke,1998,29(12):2478-2483.
[18]Boysen G, Brander T, Christensen H, et al. Homocysteine and risk of recurrent stroke. Stroke,2003,34(5):1258-1261.
[19]谈晓牧,刘建国,刘怀翔,等.高同型半胱氨酸血症与脑梗死复发率关系的随访研究.中华神经科杂志,2006，39(9)：591-594.
[20]Del Ser T, Barba R, Herranz AS, et al. Hyperhomocyst(e)inemia is a risk factor of secondary vascular events in stroke patients. Cerebrovasc Dis,2001, 12(2):91-98.
[21]Flicker L, Vasikaran SD, Thomas J, et al. Efficacy of B vitamins in lowering homocysteine in older men:maximal effects for those with B12 deficiency and hyperhomocysteinemia. Stroke,2006,37(2):547-549.
[22]Eikelboom JW, Hankey GJ, Anand SS, et al. Association between high homocyst(e)ine and ischemic stroke due to large- and small-artery disease but not other etiologic subtypes of ischemic stroke. Stroke,2000; 31 (5):1069-1075.
[23]刘永珍,尹静,于逢春,等.脑卒中患者同型半胱氨酸水平及其影响因素研究.中国神经精神疾病杂志,2009,35(2)：105-107.
[24]Wald DS, Law M, Morris JK. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ,2002,325(7374):1202.
[25]张哲成,高海风,刘建国,等.高同型半胱氨酸血症及相关因子与脑梗死相关性的研究.中国临床神经科学,2003，11(3)：272-274.
[26]Christen WG, Ajani UA, Glynn RJ, et al. Blood levels of homocysteine and increased risks of cardiovascular disease:causal or casual? Arch Intern Med, 2000,160(4):422-434.
[27]Meiklejohn DJ, Vickers MA, Dijkhuisen R, et al. Plasma homocysteine concentrations in the acute and convalescent periods of atherothrombotic stroke. Stroke,2001,32(1):57-62.
[28]Chambers JC, McGregor A, Jean-Marie J, et al. Demonstration of rapid onset vascular endothelial dysfunction after hyperhomocysteinemia:an effect reversible with vitamin C therapy. Circulation,1999,99(9):1156-1160.
[29]Van den Berg M, Boers GH, Franken DG, et al. Hyperhomocysteinaemia and endothelial dysfunction in young patients with peripheral arterial occlusive disease. Eur J Clin Invest,1995,25(3):176-181.
[30]Brattstrom L. Vitamins as homocysteine-lowering agents. J Nutr,1996,126(4 Suppl):1276S-1280S.
[31]Homocysteine Lowering Trialists'Collaboration. Lowering blood homocysteine with folic acid based supplements:meta-analysis of randomised trials. BMJ, 1998,316(7135):894-898.
[32]Wang X, Qin X, Demirtas H.et al. Efficacy of folic acid supplementation in stroke prevention: a meta-analysis. Lancet,2007,369(9576):1876-1882.
[39]神经系统疾病伴发抑郁焦虑障碍的诊断治疗专家共识组.神经系统疾病伴发抑郁焦虑障碍的诊断治疗专家共识.中华内科杂志,2008,47(1)：80-83.
[40]Pohjasvaara T, Leppavuori A, Siira Ⅰ, et al. Frequency and clinical determinants of poststroke depression. Stroke,1998,29(11):2311-2317.
[41]Whyte EM, Mulsant BH. Post stroke depression:epidemiology, pathophysiology, and biological treatment. Biol Psychiatry,2002,52(3):253-264.
[42]Verdelho A, Henon H, Lebert F, et al. Depressive symptoms after stroke and relationship with dementia: A three-year follow-up study. Neurology,2004, 62(6):905-911.
[43]Andersen G. Post-stroke depression:Diagnosis and incidence. Eur Psychiatry, 1997,12:255s-260s.
[44]Kauhanen M, Korpelainen JT, Hiltunen P, et al. Poststroke depression correlates with cognitive impairment and neurological deficits. Stroke,1999, 30(9):1875-1880.
[45]龙洁,刘永珍,蔡焯基,等.卒中后抑郁状态的发生率及相关因素研究.中华神经科杂志,2001,34(3)：145-148.
[46]Reutens S, Sachdev P. Homocysteine in neuropsychiatric disorders of the elderly. Int J Geriatr Psychiatry,2002,17(9):859-864.
[47]Bottiglieri T, Laundy M, Crellin R, et al. Homocysteine, folate, methylation, and monoamine metabolism in depression. J Neurol Neurosurg Psychiatry, 2000,69(2):228-232.
[48]Tiemeier H, van Tuijl HR, Hofinan A, et al. Vitamin B12, folate, and homocysteine in depression:the Rotterdam Study. Am J Psychiatry,2002, 159(12):2099-2101.
[49]Dimopoulos N, Piperi C, Salonicioti A, et al. Correlation of folate, vitamin B12 and homocysteine plasma levels with depression in an elderly Greek population. Clin Biochem,2007,40(9-10):604-608.
[50]Sachdev PS, Parslow RA, Lux O, et al. Relationship of homocysteine, folic acid and vitamin B12 with depression in a middle-aged community sample. Psychol Med,2005,35(4):529-538.
[51]Tolmunen T, Hintikka J, Voutilainen S, et al. Association between depressive symptoms and serum concentrations of homocysteine in men:a population study. Am J Clin Nutr,2004,80(6):1574-1578.
[52]Almeida OP, McCaul K, Hankey GJ, et al. Homocysteine and depression in later life. Arch Gen Psychiatry,2008,65(11):1286-1294.
[53]袁勇贵,李海林,吴瑞枝,等.血浆同型半胱氨酸水平及N5,N10-亚甲四氢叶酸还原酶基因多态性与老年期抑郁症的关联研究.中华精神科杂志,2005,38f31：150-153.
[54]Wesson VA, Levitt AJ, Joffe RT. Change in folate status with antidepressant treatment. Psychiatry Res,1994,53(3):313-322.
[55]Fava M, Borus JS, Alpert JE, et al. Folate, vitamin B12, and homocysteine in major depressive disorder. Am J Psychiatry,1997,154(3):426-428.
[56]Miller AL. The methylation, neurotransmitter, and antioxidant connections between folate and depression. Altern Med Rev,2008,13(3):216-226.
[57]Morris MS, Fava M, Jacques PF, et al. Depression and folate status in the US Population. Psychother Psychosom,2003,72(2):80-87.
[58]Paolucci S, Gandolfo C, Provinciali L, et al. The Italian multicenter observational study on post-stroke depression (DESTRO). J Neurol,2006, 253(5):556-562.
[59]王桂红,王拥军.卒中后抑郁障碍研究进展.中华内科杂志2008年3月第47卷第3期chin J Intern Med, march 2008,Vol47,No3.
[2]Homocysteine Studies Collaboration. Homocysteine and risk of ischemic heartdiseaseandstroke:ameta—analysis[J]. JAMA,2002,228(16):2015-2022.
[3]Wald DS,Law M,Morris JK. Homocysteine and cardiovascular disease:evidence on causality from a meta-analysis[J]. BMJ,2002,325(7374):1202.
[4]刘建国,高海风,张哲成等.高同型半胱氨酸血症与复发性脑梗死[J].天津医药,2003,31(7)：471-473.
[5]张哲成,高海风,刘建国等.高同型半胱氨酸血症及相关因子与脑梗死相关性的研究[J].中国临床神经科学,2003,11(3)：272-274.
[6]Kim JM, Stewart R, Kim SW, et al. Changes in folate, vitamin B12 and homocysteine associated with incident dementia. J Neurol Neurosurg Psychiatry, 2008,79(8):864-868.
[7]许贤豪主编.神经心理量表检测指南.北京：中国协和医科大学出版社，2007.
[8]Frick B, Schrocksnadel K, Neurauter G, et al. Rap id measurement of total plasma homocysteine by HPLC. Clin Chim Acta,2003,331:19-23.
[9]Krijt J, Vackova M, Kozich V. Measurement of homocysteine and other aminothiols in plasma:advantages of using tris (2-carboxetlhyl) phosphine as reductant compared with tri-n-butyphosphine. Clin Chem,2001,47:1821-1828.
[10]Hankey GJ, Jamrozik K, Broadhurst RJ, et al. Long-term risk of first recurrent stroke in the Perth Community Stroke Study. Stroke,1998,29(12):2491-2500.
[11]Homocysteine Studies Collaboration. Homocysteine and risk of ischemic heart disease and stroke:a meta-analysis. JAMA,2002,288(16):2015-2022.
[12]Nygard O, Nordrehaug JE, Refsum H, et al. Plasma homocysteine levels and mortality in patients with coronary artery disease. N Engl J Med,1997, 337(4):230-236.
[13]Brattstrom LE, Hardebo JE, Hultberg BL. Moderate homocysteinemia-a possible risk factor for arteriosclerotic cerebrovascular disease. Stroke,1984, 15(6):1012-1016.
[14]Brattstrom L, Lindgren A, Israelsson B, et al. Hyperhomocysteinaemia in stroke: prevalence, cause, and relationships to type of stroke and stroke risk factors. Eur J Clin Invest,1992,22(3):214-221.
[15]Coull BM, Malinow MR, Beamer N, et al. Elevated plasma homocyst(e)ine concentration as a possible independent risk factor for stroke. Stroke,1990, 21(4):572-576.
[16]Perry IJ, Refsum H, Morris RW, et al. Prospective study of serum total homocysteine concentration and risk of stroke in middle-aged British men. Lancet,1995,346(8987):1395-1398.
[17]Yoo JH, Chung CS, Kang SS. Relation of plasma homocyst(e)ine to cerebral infarction and cerebral atherosclerosis. Stroke,1998,29(12):2478-2483.
[18]Boysen G, Brander T, Christensen H, et al. Homocysteine and risk of recurrent stroke. Stroke,2003,34(5):1258-1261.
[19]谈晓牧,刘建国,刘怀翔,等.高同型半胱氨酸血症与脑梗死复发率关系的随访研究.中华神经科杂志,2006,39f9)：591-594.
[20]Del Ser T, Barba R, Herranz AS, et al. Hyperhomocyst(e)inemia is a risk factor of secondary vascular events in stroke patients. Cerebrovasc Dis,2001, 12(2):91-98.
[21]Flicker L, Vasikaran SD, Thomas J, et al. Efficacy of B vitamins in lowering homocysteine in older men:maximal effects for those with B12 deficiency and hyperhomocysteinemia. Stroke,2006,37(2):547-549.
[22]Eikelboom JW, Hankey GJ, Anand SS, et al. Association between high homocyst(e)ine and ischemic stroke due to large- and small-artery disease but not other etiologic subtypes of ischemic stroke. Stroke,2000; 31 (5):1069-1075.
[23]刘永珍,尹静,于逢春,等.脑卒中患者同型半胱氨酸水平及其影响因素研究.中国神经精神疾病杂志.,2009，,35(2)：105-107.
[24]Wald DS, Law M, Morris JK. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ,2002,325(7374):1202.
[25]张哲成,高海风,刘建国,等.高同型半胱氨酸血症及相关因子与脑梗死相关性的研究.中国临床神经科学,2003,11(3)：272-274.
[26]Christen WG, Ajani UA, Glynn RJ, et al. Blood levels of homocysteine and increased risks of cardiovascular disease:causal or casual? Arch Intern Med, 2000,160(4):422-434.
[27]Meiklejohn DJ, Vickers MA, Dijkhuisen R, et al. Plasma homocysteine concentrations in the acute and convalescent periods of atherothrombotic stroke. Stroke,2001,32(1):57-62.
[28]Chambers JC, McGregor A, Jean-Marie J, et al. Demonstration of rapid onset vascular endothelial dysfunction after hyperhomocysteinemia: an effect reversible with vitamin C therapy. Circulation,1999,99(9):1156-1160.
[29]Van den Berg M, Boers GH, Franken DG, et al. Hyperhomocysteinaemia and endothelial dysfunction in young patients with peripheral arterial occlusive disease. Eur J Clin Invest,1995,25(3):176-181.
[30]Brattstrom L. Vitamins as homocysteine-lowering agents. J Nutr,1996,126(4 Suppl):1276S-1280S.
[31]Homocysteine Lowering Trialists'Collaboration. Lowering blood homocysteine with folic acid based supplements:meta-analysis of randomised trials. BMJ, 1998,316(7135):894-898.
[32]Wang X, Qin X, Demirtas H,et al. Efficacy of folic acid supplementation in stroke prevention:a meta-analysis. Lancet,2007,369(9576):1876-1882.
[33]神经系统疾病伴发抑郁焦虑障碍的诊断治疗专家共识组寺申经系统疾病伴发抑郁焦虑障碍的诊断治疗专家共识.中华内科杂志,2008,47(1)：80一83.
[34]Pohjasvaara T, Leppavuori A, Siira I, et al. Frequency and clinical determinants of poststroke depression. Stroke,1998,29(11):2311-2317.
[35]Whyte EM, Mulsant BH. Post stroke depression:epidemiology, pathophysiology, and biological treatment. Biol Psychiatry,2002,52(3):253-264.
[36]Verdelho A, Henon H, Lebert F, et al. Depressive symptoms after stroke and relationship with dementia: A three-year follow-up study. Neurology,2004, 62(6):905-911.
[37]Andersen G. Post-stroke depression:Diagnosis and incidence. Eur Psychiatry, 1997,12:255s-260s.
[38]Kauhanen M, Korpelainen JT, Hiltunen P, et al. Poststroke depression correlates with cognitive impairment and neurological deficits. Stroke,1999, 30(9):1875-1880.
[39]龙洁,刘永珍,蔡焯基,等.卒中后抑郁状态的发生率及相关因素研究.中华神经科杂志,2001,34(3)：145-148.
[40]Robinson RG, Bloom FE. Pharmacological treatment following experimental cerebral infarction:implications for understanding psychological symptoms of human stroke. Biol Psychiatry,1977,12(5):669-680.
[41]Navines R, Martin-Santos R, Gomez-Gil E, et al. Effects of citalopram treatment on hypothermic and hormonal responses to the 5-HT1 A receptor agonist buspirone in patients with major depression and therapeutic response. Psychoneuroendocrinology,2007,32(4):411-416.
[42]Reding M, Orto L, Willensky P, et al. The dexamethasone suppression test. An indicator of depression in stroke but not a predictor of rehabilitation outcome. ArchNeurol,1985,42(3):209-212.
[43]Hackett ML, Anderson CS. Predictors of depression after stroke:a systematic review of observational studies. Stroke,2005,36(10):2296-2301.
[44]Reutens S, Sachdev P. Homocysteine in neuropsychiatric disorders of the elderly. Int J Geriatr Psychiatry,2002,17(9):859-864.
[45]Bottiglieri T, Laundy M, Crellin R, et al. Homocysteine, folate, methylation, and monoamine metabolism in depression. J Neurol Neurosurg Psychiatry, 2000,69(2):228-232.
[46]Tiemeier H, van Tuijl HR, Hofman A, et al. Vitamin B12, folate, and homocysteine in depression:the Rotterdam Study. Am J Psychiatry,2002, 159(12):2099-2101.
[47]Dimopoulos N, Piperi C, Salonicioti A, et al. Correlation of folate, vitamin B12 and homocysteine plasma levels with depression in an elderly Greek population. Clin Biochem,2007,40(9-10):604-608.
[48]Sachdev PS, Parslow RA, Lux O, et al. Relationship of homocysteine, folic acid and vitamin B12 with depression in a middle-aged community sample. Psychol Med,2005,35(4):529-538.
[49]Tolmunen T, Hintikka J, Voutilainen S, et al. Association between depressive symptoms and serum concentrations of homocysteine in men:a population study.
[50]Dimopoulos N, Piperi C, Salonicioti A, et al. Correlation of folate, vitamin B12 and homocysteine plasma levels with depression in an elderly Greek population. Clin Biochem,2007,40(9-10):604-608.
[51]Tolmunen T, Hintikka J, Voutilainen S, et al. Association between depressive symptoms and serum concentrations of homocysteine in men:a population study. Am J Clin Nutr,2004,80(6):1574-1578.
[52]Wesson VA, Levitt AJ, Joffe RT. Change in folate status with antidepressant treatment. Psychiatry Res,1994,53(3):313-322.
[53]Miller AL. The methylation, neurotransmitter, and antioxidant connections
[54]Almeida OP, McCaul K, Hankey GJ, et al. Homocysteine and depression in later life. Arch Gen Psychiatry,2008,65(11):1286-1294.
[55]袁勇贵,李海林,吴瑞枝,等.血浆同型半胱氨酸水平及N5,N10一亚甲四氢叶酸还原酶基因多态性与老年期抑郁症的关联研究.中华精神科杂志,2005,38(3)：150-153.
[1]杨玲俐,张志甜卒中后抑郁的流行病学及临床特点,中国卒中杂志,2007,2：907—10.
[2]why EM, Muleant DH.post stroke depression:epidemiology, Pathophysiology, andbidogicaltreatment Biol Psychiatry,2002,52:253-264.
[3]Pohjasvaara, LeppavuoriA, siira I, et al.Frequency and clinical determinants of Poststroke depression.Stroke,1998,29:2311—2317.
[4]Sharpe M, Hawton K, House A, et al.Mood discorders in longterm survivors of stroke:associations with brain lesion ainlesion location andvolume.Psychol Med,1990,20:815-828.
[5]paul SL, DeweyHM, Sturm JW, etal.AG,Prevalence of depression and use of antidepressant medication at 5-years poststroke in the North East Melbourns Stroke Incidence Study.Stroke,2006,37:2854-2855.
[6]Hackett ML, Yapa C, parag V, et al. Frequency of Depression after slroke:a systematic review of observational studies.Stroke,2005,36:1330-1340.
[7]许贤豪主编.神经心理量表检测指南.北京：中国仂协和医科大学出版社,2007.
[8]Frick B, Schrocksnadel K, Neurauter G, et al. Rap id measurement of total plasma homocysteine by HPLC. Clin Chim Acta,2003,331:19-23.
[9]Krijt J, Vackova M, Kozich V. Measurement of homocysteine and other aminothiols in plasma:advantages of using tris (2-carboxetlhyl) phosphine as reductant compared with tri-n-butyphosphine. Clin Chem,2001,47:1821-1828.
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