帕金森病伴发抑郁的神经递质改变

目的　探讨帕金森病 (PD)伴发抑郁的神经递质改变。方法　用抑郁自评量表 (CESD)和汉密尔顿抑郁量表 (HAMD)评出PD伴发抑郁患者 33例 ,其中轻度抑郁 2 4例 ,中、重度抑郁 9例 :另取阑尾炎、腹股沟疝气、内、外混合痔等 2 5例作为对照组。应用高效液相色谱仪 ,电化学检测器对两组患者进行了脑脊液 (CSF)中单胺类神经递质 5 羟色胺 (5 HT)的代谢产物 5 羟吲哚乙酸 (5 HIAA)和去甲肾上腺素 (NE)的代谢产物 3 甲氧基 4羟基苯乙二醇 (MHPG)的含量测定。结果　患者组CSF中的 5 HIAA和MHPG含量均低于对照组 ,P <0 .0 1,有显著性差异。结论　PD伴发抑郁的患者其CSF中 5 HIAA和MHPG含量显著减少 ,抑郁症状可能与 5 HT和 (或 )NE的缺乏有关。提示PD伴发抑郁有着相应的生化病理基础     

帕金森病外科治疗的综合评价与相关基础研究

目的通过综合研究对帕金森病(PD)外科治疗的价值和疗效进行全面评价。方法采用医学心理学测验(WAISRC)、临床记忆量表(MMPI)、神经生理学检测(听觉P300地形图)、神经电生理学(体感诱发电位SEP)和神经生化检查的脑脊液中多巴胺(DA)、5羟色胺(5HT)、去甲肾上腺素(NE)及其代谢产物)等对手术前后患者进行综合研究,并设对照组。结果手术前后智能和精神症状无显著性差异(P>0.05);手术后SEP的N20波峰潜伏期较术前缩短,统计学处理有差异(P左<0.005,P右<0.05),手术侧较非手术侧峰潜伏期缩短(P<0.05)。伴发抑郁患者组CSF中单胺类神经递质5HT的代谢产物5羟吲哚乙酸(5HIAA)和NE的代谢产物3甲氧基4羟基苯乙二醇(MHPG)低于对照组(P<0.01),患者组DA、高香草酸(HVA),5HT,5HIAA、NE、MPHG低于正常对照组(P<0.001),手术组上述各项均高于手术前组(P<0.001);结论手术不会加重智能和精神障碍;听觉P300地形图可作为诊断和疗效判定的客观指标之一;帕金森病及伴发抑郁症状均具有相应生化病理学基础。     

立体定向手术对难治性精神分裂症患者脑脊液多巴胺的影响

目的　探讨立体定向手术对难治性精神分裂症患者中枢多巴胺 (DA)代谢的影响。方法　高效液相色谱 电化学检测法 (HPLC ECD)测定 33例立体向手术治疗前后的精神分裂症患者及 30例对照者脑脊液 (CSF)中DA及高香草酸 (HVA)水平。结果　精神分裂症患者手术前CSF中DA、HVA水平显著高于对照组 (P <0 0 5 ) ;手术后DA、HAV水平显著下降 (P <0 0 5 )。结论　立体定向手术能纠正难治性精神分裂症患者中枢DA代谢的紊乱。     

立体定向毁损大鼠杏仁核及隔核对脑内单胺类递质含量的影响

目的 :探讨杏仁核及隔核毁损后AMP模型大鼠脑内单胺类递质含量的变化。方法 :经腹腔注射苯丙胺 (amphetamine ,AMP)制作精神分裂症动物模型 ,用立体定向技术电极毁损大鼠杏仁核及隔核 ,采用荧光分光光度法和放射免疫法测定大鼠前额叶、间脑和脑干多巴胺 (DA)、5 羟色胺 ( 5 HT)和去甲肾上腺素 (NE)的含量。结果 :杏仁核及隔核毁损组前额叶DA低于模型组 (P <0 0 1) ,5 HT、NE均高于模型组 (P <0 0 1) ;杏仁核及隔核毁损组间脑DA、NE均低于模型组 (P <0 0 1) ,5 HT高于模型组 (P <0 0 1) ;脑干DA、NE均低于模型组 (P <0 0 1) ,5 HT高于模型组 (P <0 0 1)。结论 :AMP模型大鼠前额叶和脑干DA含量增高、5 HT和NE含量下降 ,间脑DA、NE含量增高、5 HT含量下降 ,立体定向毁损杏仁核及隔核能够改变脑内单胺类递质的水平。     

抑郁症与血浆中单胺类神经递质代谢产物

目的 检测抑郁症患血浆中单胺递质代谢产物在抗抑郁治疗前后的差异，探讨抑郁症及抗抑郁治疗与血浆中单胺递质代谢产物浓度的相关性。方法 用高效液相色谱法对40例抑郁症患治疗前后血浆中单胺递质代谢产物的浓度进行测定，用汉密尔顿抑郁量表评定抑郁症患的临床疗效。结果 抑郁症患血浆中单胺递质代谢产物5－HIAA、MHPG、HVA的浓度均显低于正常对照组，P＜0．05。经过4周住院治疗显效，HAMD分显下降，患血浆中5－HIAA、MHPG含量与治疗前比较明显升高，有显差异，P＜0．05；但HVA没有明显变化。结论 外周的单胺递质代谢产物可反映脑中单胺类神经递质的状态，血浆中单胺递质的变化可作为抑郁症及疗效评定的一个重要参考指标。     

抑郁症患者血浆白细胞介素与单胺代谢产物的研究

目的：探讨抑郁症患抗抑郁症治疗前后的细胞免疫及单胺类神经递质代谢产物的改变。方法：采用酶联免疫吸附法和高效液相电化学检测法，对40例抑郁症患在治疗前和抗抑郁药治疗4周后的血浆细胞因子白介素2（IL－2）和白介素6（IL－6），以及单胺代谢产物5－羟吲哚乙酸（5－HIAA）、3-甲基－4－羟－苯乙二醇（MHPG）和高香草酸（HVA）的浓度进行测定，并以20名健康人作为对照组。结果：（1）抑郁症组治疗前血浆IL－2、IL－6浓度明显高于正常对照组（P＜0．01），经过4周抗抑郁剂治疗后，随着病情显好转IL－2、IL－6较治疗前显降低（P＜0．01）；（2）抑郁症组治疗前血浆T－HIAA、MHPG、HVA浓度显低于正常对照组（P＜0．05），治疗后5－HIAA、MHPG明显高于治疗前（P＜0．05）；（3）治疗前后血浆5－HIAA的差值与治疗前后IL－2、IL－6的差值均呈显的负相关（P＜0．05）。结论：（1）抑郁症患可能伴有免疫激活和炎症反应。（2）抑郁症患存在中枢5－HT和NE功能低下。（3）IL－2、IL－6可影响中枢的5－HT活动。     

抑郁症患者自杀与脑脊液单胺代谢产物的关系

目的：探讨抑郁症患者自杀与脑脊液单胺代谢产物之间的关系。方法：应用高效液相色谱法，测定24例抑郁症患者(自杀组10例，无自杀组14例)及25例对照组5-羟色胺(5-HT)代谢产物5-羟吲哚乙酸(5-HIAA)，去甲肾上腺素(NE)代谢产物3-甲基-4-羟苯乙二醇(MHPG)及多巴胺(DA)代谢产物高香草酸(HVA)的浓度。结果：抑郁症自杀组5-HIAA浓度显著低于对照组，男性自杀组5-HIAA浓度、HVA浓度和HVA／MHPG比值均显著低于男性对照组，女性则无显著差异：结论：抑郁症患者自杀可能与5-HT和DA功能低下以及DA和NE之间的关系改变有关。     

帕金森病伴发抑郁的神经递质改变

目的探讨帕金森病伴发抑郁的神经递质改变.方法用抑郁自评量表(CESD)和汗密尔顿抑郁量表(HAMD)评出帕金森病伴发抑郁患者33例,其中轻度抑郁24例,重度抑郁9例;另取阑尾炎、腹股沟疝、内、外混合痔等25例为对照组.应用日本岛津6A高效液相色谱仪,岛津电化学检测器对两组患者进行了脑脊液(CSF)中单胺类神经递质代谢产物5-羟吲哚已酸(5-HIAA)和3-甲氧-4羟苯乙二醇(MHPG)的含量测定.并进行统计处理.结果两组均数用近似法t检验,(两总体方差不齐)以-x±S表示,结果显示患者组中的5-HIAA和MHPG含量均低于对照组,差异有非常显著性.结论本组通过测定5-HT的代谢产物5-HIAA和NA的代谢产物MHPG,证实了PD伴发患者抑郁的患者其CSF中5-HIAA和MHPG含量显著减少,抑郁症状被认为与5-HT和(或)NA的缺乏有关.本文显示PD伴发抑郁有其生化病理基础.     

无先兆偏头痛患者血单胺类递质变化的研究

目的 了解5－羟色胺（5－TH）、5－羟吲哚乙酸（5－HIAA）、多巴胺（DA）、去甲肾上腺素（NE）在无先兆偏头痛发病中的作用。方法 用荧光分光光度法检测35例无先兆偏头痛患者（发作期16例、间歇期19例）和23例正常人血浆及血小板5－HT、5－HIAA、DA、NE含量。结果 无先兆偏头痛患者发作期组血浆5－HT含量低于对照组（P＜0.05),而5－HIAA含量高于对照组（P＜0.01）;间歇期组5－HT含量高于发作期组,而5－HIAA含量低于发作期组（P＜0.01）;发作期组血浆DA、NE含量均低于对照组（P＜0.01）间歇期组血浆DA与发作期组相比亦有显著性差异（P＜0.01）。无先兆偏头痛患者发作期组血小板5－HT含量高于对照组和间歇期组,而5－HIAA含量低于对照组和间歇期组（P＜0.01）;而发作期组血小板NE含量高于对照组和间歇期组（P＜0.01）;DA含量则低于对照组和间歇期组（P＜0.01）。结论 单胺类递质对偏头痛的发生可能有重要意义。     

精神分裂症患者的中枢多巴胺和5—羟色胺浓度及其性别差异

目的 了解精神分裂症中枢多巴胺（DA）与5－羟色胺（5－HT）相互作用的变化及其性别影响的程度。方法 应用高效液相色谱对符合CCMD－2精神分裂症诊断标准的30例男性病人、37例女性病人、21例男性对照组、9例女性对照组脑脊液中DA、5－HT及其代谢产物高香草酸（HVA）、5－羟吲哚乙酸（5－HIAA）进行测试,并应用5－HT／DA、5－HIAA／HVA作为它们的相互作用的指标。结果 5－HT／DA、5－HIAA／HVA在4组中有显著性差异（F＝3．567,P＝0．032;F＝12．464,P＝0．001）,进一步分析提示;女性分裂症5－HT／DA显著低于男性对照组,且男性、女性分裂症及男性对照组5－HIAA／HVA均显著低于女性对照组。在男性病例组的相关分析中,5－HT／DA与BPRS及其阳性症状呈显著负漠、非特异性症状呈显著负、正相关;5－HIAA／HVA与思维形式障碍呈显著正相关。结论 精神分裂症患者存在中枢DA和5－HT相互作用的失平衡,这种失平衡与某些重要精神症状有关,且受性别因素的影响。     

Concentrations of monoamines and monoamine metabolites in cerebrospinal fluid determined by high-performance liquid chromatography with electrochemical detection

Using reversed-phase high-performance liquid chromatography with an electrochemical detection, I have developed a sensitive technique to measure monoamines and their metabolites in cerebrospinal fluid (CSF). The present method has been shown to offer simplicity and high sensitivity for the determination of dopamine (DA) and norepinephrine (NE), as well as monoamine metabolites, in small amounts of human CSF. The first 2 ml of CSF was obtained from 61 patients (27 males and 34 females), aged from 15 to 88 years, with a variety of non-neurological diseases by lumbar puncture performed between 8:45 a.m. and 4:20 p.m. CSF was collected in the lateral decubitus position before lumbar anesthesia for surgical treatment. Samples were immediately frozen at -80 degrees C until assayed. None had any history of neurological or psychiatric illness. Concentrations in lumbar CSF were 10.9 +/- 6.0 pg/ml (mean +/- SD, n = 22) for DA, 105.8 +/- 63.6 pg/ml (n = 60) for NE, 30.5 +/- 1.6 ng/ml (n = 61) for homovanillic acid (HVA), 1.8 +/- 1.2 ng/ml (n = 46) for 3,4-dihydroxyphenylacetic acid (DOPAC), 7.7 +/- 2.1 ng/ml (n = 46) for 3-methoxy-4-hydroxyphenylglycol (MHPG) and 18.8 +/- 10.9 ng/ml (n = 61) for 5-hydroxyindoleacetic acid (5 HIAA), respectively. While 5 HIAA concentrations in lumbar CSF taken in the afternoon tended to be lower than those in the morning, MHPG in the afternoon was significantly higher than that in the morning. There were no sex differences in the concentrations of monoamines and their metabolites examined. There was a tendency for the concentrations of HVA and DOPAC to be lower in older subjects. A significant correlation was found among HVA, 5 HIAA and MHPG concentrations in lumbar CSF. The present study suggests that a standardized condition for collecting CSF should be employed to compare the concentrations of monoamines and their metabolites across central nervous system disorders. Furthermore, in addition to the measurement of individual monoamine or monoamine metabolite level in CSF, future studies should be extended to include comparisons of a mutual relationship among several monoamine metabolites.     

Aggression in humans correlates with cerebrospinal fluid amine metabolites.

Cerebrospinal fluid of the major central metabolites of serotonin (5HT), norepinephrine (NE), and dopamine (DA)--5-hydroxyindoleacetic acid (5HIAA), 3-methoxy-4-hydroxy=phenylglycol (MHPG), and homovanillic acid (HVA), respectively--were studied in a group of 26 age-similar military men with no history of major psychiatric illness, but with various personality disorders and difficulties adjusting to military life. Independently scored history of aggressive behavior showed a significant negative correlation with 5HIAA (r = -0.78) and a significant positive correlation with MHPG (r = 0.64).     

MONOAMINES (SEROTONIN AND CATECHOLAMINES) AND THEIR DERIVATIVES IN INFANTILE AUTISM: AGE-RELATED CHANGES AND DRUG EFFECTS

Levels of dopamine (DA) and its derivatives homovanillic acid (HVA), 3-4 dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3MT) and norepinephrine+epinephrine (NE + E), and serotonin (5HT) and its derivative 5-hydroxyindolacetic acid (5HIAA) were determined from the urine of 156 autistic children aged two to 12 years 6 months, and compared with those of age-matched mentally retarded non-autistic and normal controls. Very significant group and age effects were found for DA, HVA, 3MT, NE + E and 5HT. High HVA, 3MT, NE + E and 5HT levels were found in autistic and non-autistic children. The DA, HVA, 3MT, NE + E, 5HT and 5HIAA levels decreased significantly with age in the three groups. Significantly decreased levels of DA and HVA were observed in autistic children on haloperidol, compared with non-medicated autistic children. The results are discussed in relation to the hypothesis of a maturation defect of monoaminergic systems in autism.     

巴曲酶对脑缺血再灌注细胞外液单胺类及其代谢产物的影响——微透析研究

目的巴曲酶对脑缺血再灌流损伤的保护机理。方法采用脑内微透析技术结合高灵敏度的高压液相色谱－电化学检测手段（ＨＰＬＣ－ＥＤ），测定前脑缺血３０ｍｉｎ再灌注１２０ｍｉｎ时的纹状体细胞外液（ＥＣＦ）的ＤＡ、５－ＨＴ和ＮＥ及其代谢产物（５－ＨＩＡＡ）和ＨＶＡ的变化和巴曲酶的影响。结果显示脑缺血时，ＥＣＦＤＡ、ＮＥ及５－ＨＴ明显升高，巴曲酶能显著地降低脑缺血时ＥＣＦＤＡ及再灌注时ＥＣＦＨＶＡ和５－ＨＩＡＡ的水平。结论巴曲酶影响单胺神经递质是对脑缺血再灌注损伤起保护作用的机理之一     

Cerebrospinal fluid levels of monoamine metabolites in panic disorder.

The cerebrospinal fluid (CSF) levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5HIAA), the noradrenaline metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG), and the dopamine metabolite homovanillic acid (HVA) did not differ significantly in a group of patients with panic disorder (n = 17) as compared to age- and sex-matched normal controls (n = 17). While CSF concentrations of HVA and 5HIAA were significantly correlated in both patients and controls, CSF MHPG levels were significantly correlated with the concentrations of CSF 5HIAA and HVA only in patients. In a small number of subjects (n = 5), successful reduction of anxiety attacks by administration of clomipramine or imipramine (50-150 mg/day) for at least 2 months was associated with a significant decrease in CSF concentrations of 5HIAA and MHPG, but not HVA.     

Monoamine metabolites in lumbar CSF: the question of their origin in relation to clinical studies

The sources of homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) and 5-hydroxyindoleacetic acid (5HIAA) in lumbar CSF of man are discussed. Although HVA in lumbar CSF is derived from the brain, and MHPG seems to be mainly from the spinal cord, the origin of 5HIAA is uncertain. The evidence for and against a brain contribution to 5HIAA of the lumbar CSF is evaluated. It is concluded that the brain can contribute 5HIAA to lumbar CSF under some circumstances. Measurement of 5HIAA concentrations in lumbar CSF can be of clinical value in detecting changes of 5-hydroxytryptamine (5HT) metabolism in the CNS if the changes are general throughout the CNS.     

CSF monoamine metabolite levels in Alzheimer's and Parkinson's disease

Levels of the monoamine metabolites homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) were measured in lumbar CSF from 32 patients with a clinical diagnosis of Alzheimer's disease (AD) and from 21 patients with Parkinson's disease (PD). The baseline CSF metabolite values did not differ significantly between the two groups of patients, although HVA levels were lowest in patients with PD and in the more severely demented patients with AD. Levels of all three metabolites increased significantly in both patient groups during probenecid administration, but HVA levels were significantly higher in patients with AD than in patients with PD. Within the AD group, those with the most severe dementia had the greatest rise in MHPG levels. Alterations in monoamine metabolite levels in the CSF detected during probenecid administration aid in the differential diagnosis of neurodegenerative diseases such as AD.     

Reproducibility of monoamine metabolite measurements in human cerebrospinal fluid

The levels of homovanillic acid (HVA), 5-hydroxy indoleacetic acid (5HIAA), and 3-methoxy-4-hydroxy phenylglycol (MHPG) were determined in the cerebrospinal fluid (CSF) of 28 patients with cognitive disorders on Day 1 and Days 8 or 15. During that period all patients were kept hospitalized under strict standard conditions, did not develop any acute CNS lesion, had no changes in their treatment and no acute systemic disease. The mean levels found in the first and second determinations were almost identical for the 3 metabolites; respectively 37.8 ng/ml and 36.3 ng/ml for HVA, 27.8 ng/ml and 27.9 ng/ml for 5HIAA, and 12.9 ng/ml and 12.3 ng/ml for MHPG. Thus, the mean values of these metabolites in CSF are reproducible at least during a 15-day hospitalization. However statistically significant individual changes in metabolite levels were found between the two samples in 82% of patients for HVA, 32% for HIAA and 48% for MHPG. The number of patients required to detect a significant change in the mean levels of each monoamine metabolite has been calculated taking into account the extent of intraindividual variations.