帕金森病患者立体定向手术前后脑脊液单胺类递质含量的改变

目的　研究帕金森病 (PD)患者脑立体定向手术前后脑脊液 (CSF)中单胺类递质含量的变化。方法测定 2 6例原发性PD患者 (PD组 )脑立体定向术前、后CSF中多巴胺 (DA)、5 羟色胺 (5 HT)、去甲肾上腺素 (NE)及其代谢产物高香草酸 (HVA)、5 羟吲哚乙酸 (5 HIAA)、3 甲氧基 4羟基苯乙二醇 (MHPG)的含量 ,另外测定 2 5例外科疾病腰麻手术患者 (对照组 )CSF中HVA、5 HIAA、MHPG含量。结果　PD组CSF中HVA、5 HIAA、MHPG含量明显低于对照组 (P <0 0 0 1、P <0 0 5、P <0 0 0 1) ;手术后组的CSF中DA、HVA ,、5 HT、5 HIAA、NE、MHPG含量明显高于手术前组 (其中DA、HVA、5 HT、5 HIAA和NE均P <0 0 0 1;MHPGP <0 0 5 )。结论　PD患者CSF单胺类神经递质代谢产物含量明显降低 ,脑立体定向术可提高PD患者脑部单胺类神经递质及其代谢产物的含量 ,其发生机制可能与DA能神经元的保护作用有关     

CSF monoamine metabolites and somatostatin in Alzheimer's disease and major depression.

Decreased cerebrospinal fluid (CSF), somatostatinlike immunoreactivity (SLI) and alterations in the CSF monamine metabolites 3-methoxy-4-hydroxyphenylethylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) have been reported in patients with probable Alzheimer's disease (AD) and in patients with major depression. In this study, we found CSF SLI to be significantly lower in a large group of AD patients (n = 60) and in a group of age-matched patients with major depression (n = 18) as compared with normal controls (n = 12). Mean CSF, MHPG, 5-HIAA, and HVA levels were not significantly different among diagnostic groups. Within a group of "depressed" AD patients, CSF levels of 5-HIAA showed a significant positive correlation (p = 0.03) with CSF SLI; a similar relationship was found within the group of patients with major depression. Further exploration of the relationship between the somatostatin and serotonin systems may provide clues as to how neuropeptides interact with monoamine neurotransmitters and what role they have in depression.     

CSF monoamine metabolites in mania

As part of the National Institute of Mental Health Clinical Research Branch Collaborative Program on the Psychobiology of Depression, the authors compared concentrations of CSF monoamine metabolites (the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol [MHPG], the dopamine metabolite homovanillic acid [HVA], and the serotonin metabolite 5-hydroxyindoleacetic acid [5-HIAA]) from 14 hospitalized manic patients with concentrations from 62 healthy comparison subjects. The manic patients had significantly higher levels of MHPG. Levels of 5-HIAA and HVA did not differ between the manic patients and the comparison male subjects, but they were elevated in the female manic patients. MHPG was the only metabolite that correlated significantly with mania symptom ratings. These data are consistent with findings that have shown abnormal, perhaps excessive, central noradrenergic activity in patients with mania, but not with those suggesting deficits in serotoninergic function.     

Cerebroventricular size and cerebrospinal fluid monoamine metabolites in schizophrenic patients and healthy volunteers

Computed tomography (CT) measures and cerebrospinal fluid (CSF) levels of the monoamine metabolites homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylglycol (MHPG), and 5-hydroxyindoleacetic acid (5-HIAA) were determined in 43 healthy volunteers and in 26 patients with an acute psychosis of the schizophrenic type. There were no differences in the mean CSF levels of monoamine metabolites between the two groups. However, the patients had significantly wider lateral and third ventricles as compared to the volunteers. In the volunteers there were no significant correlations between ventricular sizes and monoamine metabolite levels, whereas in the patients a significant negative correlation was obtained between the size of the lateral ventricles and the levels of HVA and 5-HIAA in the CSF. These results may indicate that the enlargements of the brain ventricles found in a subgroup of schizophrenic patients may be associated with deficiencies in central monoamine transmission mechanisms.     

Susceptibility to neuroleptic malignant syndrome in Parkinson's disease

OBJECTIVE: To determine susceptibility to neuroleptic malignant syndrome (NMS) in patients with PD in relation to central monoamine metabolism. METHODS: CSF levels of homovanillic acid (HVA), 3-methoxy-4-hydroxy phenyletilene glycol (MHPG), and 5-hydroxyindole acetic acid (5-HIAA) were assayed in 98 PD patients (mean age, 77.2 years), including 11 patients with a prior NMS-like episode, by high-performance liquid chromatography with electrochemical detection. RESULTS: Patients with a previous NMS-like episode had worse parkinsonian disability as measured by Hoehn & Yahr scale (3.7 +/- 0.8 versus 3.0 +/- 1.1; p = 0.038) and lower CSF HVA levels (20.9 +/- 17.3 versus 44.7 +/- 22.2 ng/mL; p = 0.001) compared to those without, despite similar age, disease duration, and daily dosages of antiparkinsonian drugs between groups. Logistic regression analysis showed that the CSF HVA level (p = 0.008), but not 5-HIAA level (p = 0.621), was significantly and independently related to NMS, and that the MHPG level (p = 0.070) was tendentially associated with the disorder. Odds ratios (95% confidence intervals) corresponding to 10 ng/mL increment in CSF HVA, MHPG, and 5-HIAA levels were 0.30 (0.13 to 0.73), 4.03 (0.89 to 18.2) and 1.29 (0.47 to 3.58), respectively. CONCLUSIONS: Central dopaminergic and possible noradrenergic activity contributes to NMS development in an elderly population of PD patients. Measuring CSF levels of monoamine metabolites may provide a means for identifying NMS susceptibility in PD patients.     

CSF and urinary biogenic amines and metabolites in depression and mania. A controlled, univariate analysis

Levels of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) in the CSF, and norepinephrine (NE), epinephrine (E), vanillylmandelic acid, normetanephrine, metanephrine, and MHPG in the urine, were measured in 151 hospitalized patients with affective disorders and in 80 healthy controls following a two-week drug-free period. Unipolar and bipolar depressed subjects differed only in NE and E levels. Compared with controls, depressed subjects had higher CSF MHPG levels, women had higher 5-HIAA levels, and men had lower HVA levels. All urinary metabolites were elevated in depression and mania, with the exception of MHPG. The patterns of NE-E differences discriminated among the forms of affective disorders. These data suggest an imbalance of monoamine transmission in depression, characterized by the hyperactive sympathetic nervous system and adrenal medulla. However, MHPG may not be the measure of choice to reflect this imbalance, necessitating measurement of total body monoamine output.     

Dopamine metabolism and disposition in schizophrenic patients. Studies using debrisoquin

Debrisoquin sulfate, a monoamine oxidase inhibitor that does not enter the brain, was administered to 23 schizophrenic subjects. Plasma, cerebrospinal fluid (CSF), and urine samples were obtained before and during debrisoquin administration and were assayed for their content of norepinephrine and dopamine metabolites, ie, 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid (HVA), and dihydroxyphenylacetic acid. The severity of the patient's schizophrenic symptoms was also assessed with several types of rating scales. During debrisoquin administration there were significant reductions in plasma, urine, and CSF MHPG levels. Regression analyses suggested that the reduction in CSF MHPG level was probably due to the reduction in plasma MHPG level, which contributes to the CSF MHPG pool. Debrisoquin administration was not associated with changes in CSF HVA level, although it did produce marked reductions in plasma and urinary HVA and dihydroxyphenylacetic acid levels. Significant correlations between plasma and CSF concentrations of HVA were noted during, but not before, debrisoquin administration. Before debrisoquin administration there were trends toward positive relationships between symptom severity and plasma HVA concentrations, which became stronger and statistically significant during debrisoquin administration. These data suggest that debrisoquin may be used as a research tool to create a condition in which measures of HVA in peripheral body fluids reflect dopamine system function and metabolism within the central nervous system.     

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.     

Neuropsychological test performance and CSF levels of monoamine metabolites in healthy volunteers and patients with Alzheimer's dementia

Fifteen patients (51-78 yrs) with mild to moderately severe Alzheimer's dementia and 18 healthy subjects of the same age were examined by clinical rating scales and a battery of neuropsychological tests. Levels of the monoamine metabolites homovanillic acid (HVA), 3-methoxy-4-hydroxyphenyl glycol (MHPG) and 5-hydroxyindoleacetic acid (5-HIAA) were determined in the lumbar cerebrospinal fluid (CSF). Correlations between clinical, psychological and biochemical measures were calculated in order to elucidate whether monoaminergic mechanisms are of importance for the maintenance of cognitive abilities in normal and pathological aging. The patients' performance was severely impaired in all neuropsychological tests. The mean levels of monoamine metabolites, however, did not differ between patients and volunteers. The correlations between psychological test scores and CSF metabolite levels were generally low, but mostly negative, associating a poor performance to a high activity of brain monoaminergic neurons. Thus, among the volunteers high 5-HIAA and MHPG levels correlated with poor performance in the Picture completion and the Trail making tests--measures of visuo-perceptual and visuo-motor skills. In the demented patients poor performance in the memory tests was associated with high levels of HVA and 5-HIAA. The results indicate that monoamine neuron activity is not a primary determinant for cognitive abilities in healthy elderly subjects or in demented patients. The slight negative correlation between cognitive function and metabolite concentrations in the patients may reflect a disturbance in a dopaminergic-cholinergic balance due to degenerative changes of central cholinergic pathways.     

Biogenic amine metabolism in Tourette syndrome.

Biogenic amine metabolism in the central nervous system of 9 children with Tourette syndrome was evaluated by quantitation of their metabolites in cerebrospinal fluid by a gas chromatographic/mass spectrometric method. Homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) were measured in CSF before and after oral administration of probenecid. Dopamine metabolism appeared defective, as both baseline and accumulated levels of HVA after probenecid were decreased. Serotonin metabolism also appeared defective in some patients with low baseline and low accumulated levels of 5-HIAA after probenecid. Taken together with other clinical features of this disease, the results suggest an underlying disorder of dopamine and serotonin metabolism in Tourette syndrome.     

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.     

Neurochemical markers in the cerebrospinal fluid of patients with Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis and normal controls

Summary Several neurotransmitter markers were investigated in the cerebrospinal fluid (CSF) from patients with Alzheimer's disease (AD) (n=27), Parkinson's disease (PD) (n=35) and ALS (n=26) and from control subjects (n=34) to compare the possible alterations in the biochemical profiles of these different neurodegenerative diseases. The main proportion of the patients represented an early phase of the illness at the time of the diagnosis. Correlations of the degree of dementia and the stage of the disease with CSF measures were evaluated. The CSF levels of somatostatin like-immunoreactivity (SLI) were significantly reduced in AD patients when compared with those of normals and ALS patients. The CSF concentrations of homovanillic acid (HVA) were significantly decreased for PD patients and the decrease focused on the nondemented patients. A trend of decreasing HVA values towards the most advanced stage of Parkinson's disease assessed by Webster's scale was also displayed. The content of 3-methoxy-4-hydroxyphenylglycol (MHPG) in the CSF was higher for ALS patients than for other groups. The lowest 5-hydroxy-indoleacetic acid (5HIAA) levels were observed in the PD group and the lowest acetylcholinesterase (AChE) activities were found in the PD patients with the most severe disease. Changes in CSF measures were too subtle to be beneficial for diagnostic purposes, but adequate for reflecting the different neurochemical profiles of these three degenerative neurological disorders.     

CSF monoamine metabolites in schizophrenic patients

The monoamine metabolites 3-methoxy-4-hydroxyphenyglycol (MHPG), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were measured in the cerebrospinal fluid (CSF) of 16 psychiatrically health controls and in 28 schizophrenic patients. There was no difference in CSF MHPG and HVA levels between the group of patients and the controls. CSF levels of 5-HIAA were significantly lower in schizophrenic patients than in controls. Differential analysis of patients with and without neuroleptics revealed that these findings were not due to drug treatment. Positive correlations were found between the level of 5-HIAA and the items: hallucinatory behaviour, grandiosity, and tension as rated on the Brief Psychiatric Rating Scale. As 5-HIAA CSF data are controversial for nosological entities, the search for correlations between 5-HIAA and individual psychopathological variables could provide more specific indices for psychiatric diagnosis, treatment or prophylaxis.     

A prospective study of the association of cerebrospinal fluid monoamine metabolite levels with lethality of suicide attempts in patients with bipolar disorder

Objectives:  Bipolar disorder is a severe illness that is associated with suicidal behavior. A biological predictor of highly lethal suicide attempts in patients with bipolar disorder would be valuable. We hypothesized that cerebrospinal fluid (CSF) monoamine metabolite levels are related to lethality of suicide attempts in bipolar patients and examined the relation between CSF 5-hydroxyindolacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) levels and maximum lethality of suicide attempts at baseline and during a 2-year follow up.
Methods:  Twenty-seven bipolar depressed patients participated in the study. Demographic and clinical parameters were examined and recorded. Lumbar punctures were performed and CSF 5-HIAA, HVA, and MHPG were assayed by high-performance liquid chromatography with electrochemical detection. Following discharge, patients were evaluated after 3 months, 1 year, and 2 years. Each follow-up interview included an in-depth assessment of suicidal behavior during the intervening time period.
Results:  Six subjects made suicide attempts during the 2-year follow-up. Bipolar patients who attempted suicide during the follow-up period had higher aggression and hostility scale scores compared to bipolar subjects who did not make a suicide attempt during the follow-up period. CSF 5-HIAA, HVA, and MHPG levels were negatively correlated with the maximum lethality of suicide attempts during the 2-year follow-up period.
Conclusions:  Our finding is the first observation that CSF monoamine metabolite levels may be predictors of lethality of suicide attempts in patients with bipolar disorder. Further studies are necessary to answer the question whether CSF monoamine metabolite levels are clinically useful biochemical predictors of highly lethal suicide attempts or completed suicides.     

Seasonal variations of human lumbar CSF neurotransmitter metabolite concentrations

While circadian rhythms of many biological processes have been well characterized in humans, variations throughout the year have been little studied. Lumbar cerebrospinal fluid (CSF) neurotransmitter metabolite levels for homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenyl glycol (MHPG) were determined in patients with schizophrenia and Alzheimer's disease. Samples from both groups taken during October through March had significantly higher levels of HVA and 5-HIAA, but not MHPG, than samples from April through September.     

CSF monamine metabolites in movement disorders and normal aging

We measured four monoamine metabolite levels in CSF before and after probenecid administration to normal controls and to patients with Huntington's disease (HD), dystonia, and tardive dyskinesia. We identified differences only for the dopamine metabolite homovanillic acid (HVA), which showed increased baseline values and decreased turnover in normal aging, but decreased baseline values and normal turnover in HD. These results suggest that dopamine neurons are linked both to normal aging and to HD and that CSF HVA studies can distinguish differences in the functioning of dopamine neurons in normal aging and HD.     

Biochemical alterations during medication withdrawal in Parkinson's disease with and without neuroleptic malignant-like syndrome

The object was to assess alterations in CSF concentrations of monoamine metabolites during withdrawal of medication in patients with Parkinson's disease in relation to the presence or absence of episodes resembling neuroleptic malignant syndrome (NMS). This syndrome is a fatal condition developing after neuroleptic therapy, and a neuroleptic malignant-like syndrome (NMLS) may also occur after withdrawal of antiparkinsonian drugs in patients with Parkinson's disease. Previous biochemical assays showed that the CSF concentration of the dopamine metabolite homovanillic acid (HVA) is an independent prognostic factor for development of NMLS in patients with Parkinson's disease. In the present study, CSF concentrations of HVA, the noradrenaline (norepinephrine) metabolite 3-methoxy-4-hydroxyphenylethylene glycol, and the serotonin metabolite 5-hydroxyindole acetic acid were assayed using high performance liquid chromatography with electrochemical detection. The study population consisted of nine patients with Parkinson's disease with NMLS and 12 without NMLS, in whom metabolites were assayed during both withdrawal and remedicated periods. Concentrations of HVA in the CSF were significantly lower during the withdrawal period than the medicated period regardless of whether patients developed NMLS, and HVA concentrations were comparably increased after remedication in both groups. However, HVA concentrations were significantly lower in patients with NMLS than in those without NMLS during both withdrawal and medicated periods. Other metabolites showed no significant differences. The present data provide further biochemical evidence for extremely suppressed central dopaminergic activity during NMLS, which may indicate a narrow safety margin for medication withdrawal in patients with Parkinson's disease.     

Concentration gradient of CSF monoamine metabolites in children and adolescents

Whether the lumbar cerebrospinal fluid (CSF) concentration gradient of monoamine metabolites found in adults is influenced by age or pubertal status was studied in 26 children ranging from 6.5 to 17.3 years of age. Homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) were assayed by high-power liquid chromatography (HPLC) with electrochemical detection. Eight patients were prepubertal (Tanner stage I). The slopes in units of picomoles/milliliter/milliliter for regression lines for CSF monoamine metabolite concentrations versus milliliter of CSF collected were 5.07 +/- 0.65, 10.13 +/- 2.0, and 0.67 +/- 0.22 for 5-HIAA, HVA, and MHPG, respectively, for the group as a whole. Significant correlations with age, height, weight, or Tanner stage were not found for the HVA or MHPG concentration gradients. Tanner stage and 5-HIAA slope were significantly correlated. Three of eight prepubertal patients had nonsignificant 5-HIAA gradients. CSF studies in pediatric populations must control for aliquot collected, as the size of the gradient could produce differences sufficient to mimic a "positive" clinical study if the aliquots collected are not the same.     

Monoamine metabolites in cerebrospinal fluid during and after acute cerebral ischemia

In order to understand the role of monoamines in cerebral ischemia, 3-methyoxy-4-hydroxyphenylglycol(MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid(HVA), the three major unconjugated monoamine metabolites in cerebrospinal fluid (CSF), of 33 patients and 18 controls were measured with high performance liquid chromatography. Results showed all three metabolites were raised in patients with severe ischemia, but only MHPG and 5-HIAA were elevated significantly, MHPG changes more quickly and regularly as a consequence of cerebral ischemia than the two others. A positive correlation between any pair of metabolites was found in controls and in patients in the first week after stroke, but not at the end of the second week. Computer assisted multivariate analysis indicated 5-HIAA and MHPG correlated more closely with the state of illness in the acute stage, whereas HVA correlated the least. Possible explanations for the changes of CSF levels of amine metabolites are discussed.     

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。