Concentration of 5-hydroxyindoleacetic acid, homovanillic acid, and tryptophan in the cerebrospinal fluid of depressed patients before and after ECT.

Cerebrospinal fluid (CSF) levels of 5-hydroxyindoleacetic acid (5HIAA), tryptophan (TRYP), and homovanillic acid (HVA), were determined prior to electroconvulsive therapy (ECT) and after an average course of 6.7 ECT in six endogenous depressed patients. Depression rating scale (DRS) scores were also obtained by a "blind" research psychiatrist before and after ECT at the time of each lumbar puncture. ECT markedly reduced DRS scores but did not significantly alter CSF levels of 5HIAA, TRYP, or HVA. We found no correlation between ECT-induced DRS score reductions and changes in any of the CSF constituents studied, or between the absolute DRS score and the corresponding CSF concentration of any of the compounds. These data are consistent with those previously reported for ECT and do not suggest that ECT alters cerebral amine metabolism in depressed patients. Neither do they provide any evidence for direct amine mediation of the depression-relieving effects of ECT in man, nor for any relation between severity of depressive illness and CSF concentrations of 5HIAA, TRYP, or HVA.     

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     

Low HVA and normal 5HIAA CSF levels in drug-free schizophrenic patients compared to healthy volunteers: correlations to symptomatology and family history

Cerebrospinal fluid (CSF) levels of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5HIAA) were determined in 40 drug-free schizophrenic patients and 21 healthy volunteers by a mass fragmentographic method. Twenty-one of the schizophrenic patients were first admissions who had never received neuroleptics. Significantly, lower levels of HVA but not 5HIAA were found in the patient group, and no difference was found between chronic, previously neuroleptic-treated and never-medicated patients. HVA levels correlated positively with social interest and total positive scores on the Nurses Observation Scale for Inpatient Evaluation (NOSIE-30) and negatively with lassitude and slowness of movements on the Comprehensive Psychopathological Rating Scale (CPRS). Low levels of 5HIAA were correlated to the CPRS items delusions and apparent sadness. There were slightly higher CSF levels of 5HIAA in patients with a family history of schizophrenia, but no such difference was seen for HVA. In both schizophrenic and control subjects CSF levels of HVA and 5HIAA showed a strong intraindividual correlation. The results indicate decreased central nervous system dopaminergic turnover in schizophrenia which seems to be associated with "negative" symptomatology.     

阴性精神分裂症认知功能改善与HVA和5-HIAA的关系

目的：探讨阴性精神分裂症认知功能的改善与ＨＶＡ和５－ＨＩＡＡ变化的关系。方法：对１３例阴性精神分裂症在氯氮平治疗前和治疗８周后分别采用韦氏成人记忆量表（ＷＭＳ）,数字划消测验和威期康星卡片分类测验（Ｗｉｓｃｏｎｓｉｎ ｃａｒｄ ｓｏｒｔｉｎｇ ｔｅｓｔ,ＷＣＳＴ）评估其记忆、注意及执行功能,采用高效液相色谱－电化学检测测定其治疗前和治疗后脑脊液中ＤＡ代谢产物高香草酸（ＨＶＡ）和５－ＨＴ代谢产物五羟     

A double-blind study of zimelidine, a serotonin uptake inhibitor, and desipramine, a noradrenaline uptake inhibitor, in endogenous depression. II. Biochemical findings

In a comparative evaluation of zimelidine, a potent serotonin (5-HT) uptake inhibitor, and desipramine, a potent noradrenaline (NA) uptake inhibitor, 65 hospitalized patients with endogenous depression were evaluated for the following biochemical variables: 5-HT uptake in platelets, 5-HT concentration in whole blood, inhibition of the 5-HT and NA accumulation in rat hypothalamic synaptosomes incubated in the patients' plasma, the excretion of 4-hydroxy-3-methoxyphenyl glycol (HMPG) in urine and the pretreatment levels of the amine metabolites 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and HMPG in cerebrospinal fluid (CSF). results of the biochemical studies confirmed that zimelidine and desipramine have different profiles with respect to monoamine uptake. Thus zimelidine caused more marked inhibition of 5-HT uptake than desipramine, especially in rat brain synaptosomes incubated in the patient's plasma. Desipramine plasma was much more effective than zimelidine plasma in inhibiting NA uptake in the same preparation. The urinary excretion of HMPG decreased significantly during desipramine treatment but remained unchanged during zimelidine treatment. The combined clinical and biochemical results indicated that patients with low pretreatment levels of 5-HIAA and HVA in CSF responded significantly better to zimelidine than patients with high levels of 5-HIAA and HVA. On the other hand, patients with high levels of 5-HIAA and HVA. On the other hand, patients with high levels of HMPG in CSF tended to respond better to desipramine than those with low levels of this NA metabolite.     

Platelet MAO activity and monoamine metabolites in cerebrospinal fluid in depressed and suicidal patients and in healthy controls

Platelet monoamine oxidase (MAO) activity and cerebrospinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid (5HIAA), homovanillic acid (HVA), and 4-hydroxy-3-methoxyphenylglycol (HMPG) were simultaneously measured in 20 currently depressed patients, 11 recovered depressed patients, 15 nondepressed suicide attempters, and 42 healthy control subjects. Both 5HIAA and HVA were positively and significantly correlated to platelet MAO activity in the healthy subjects, but not in any of the patient groups. Suicide attempters had significantly lower CSF 5HIAA than nonsuicidal patients.     

CSF amine metabolites and depression

Cerebrospinal fluid (CSF) amine metabolites were measured in 37 male subjects with major depressive disorder. Scores on the Hamilton Rating Scale for Depression (HRSD) correlated significantly with 5-hydroxyindoleacetic acid (5HIAA) and with homovanillic acid (HVA). In addition, the single suicide item of the HRSD correlated significantly with 5HIAA. Further, 5HIAA and HVA correlated significantly with each other. There was a significant positive correlation between HVA and two HRSD items, the depersonalization/derealization item and the paranoid item. Since lumbar CSF metabolite concentrations may reflect central nervous system activity of parent amines, these data suggest a relationship between depression and decreased dopaminergic and serotonergic activity.     

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.     

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.     

CSF levels of neurotransmitters in Alzheimer-type dementia. Effects of ergoloid mesylate

The cerebrospinal fluid level of homovanilic acid (HVA), 5 hydroxyindolacetic acid (5HIAA) and 3 methoxy-4-hydroxy phenylglycol (MHPG) was determined twice at 12 to 15-day intervals in 23 patients with Alzheimer-type dementia (ATD). No correlation was found with the degree of dementia as assessed by psychometric testing. In most of the patients, the CSF levels of 5HIAA, MHPG and to a lesser extent HVA were found to be rather stable within a period of 2 weeks. The observation of a decrease in the concentration of HVA but not of 5HIAA or MHPG in 10 out of 12 patients treated with ergoloid mesylate may therefore be of interest in elucidating the mechanism of action of this drug in ATD.     

Homovanillic acid and 5-hydroxyindole-acetic acid in the csf of patients after a severe head injury. I. Lumbar csf concentration in chronic brain post-traumatic syndromes.

Lumbar CSF concentrations of homovanillic acid (HVA) and 5-hydroxyindole-acetic acid (5HIAA) have been determined in ten patients suffering from chronic brain post-traumatic syndromes, at various length of time after the brain trauma. Lower concentrations of HVA (mean 21 +/- 14 mug/ml) compared to controls (mean 46 +/- 10 mug/ml) was observed in 7 cases; 5HIAA levels were within normal values. The 5HIAA/HVA ratio (1.59 +/- 0.66) was significantly higher (p less than 0.001) than the one recorded in controls (0.66 +/- 0.10). Monitoring of lumbar HVA and 5HIAA over time, before, during and after L-dopa treatment, revealed interesting correlations between modification of clinical picture and the levels of monoamines acid metabolites. The data indicate a profound alteration of brain monoamines in chronic syndromes following a severe head injury and suggest that measurements of lumbar HVA and 5HIAA in these patients may be of euristic and diagnostic value.     

Effects of clomipramine treatment on cerebrospinal fluid monoamine metabolites and platelet 3H-imipramine binding and serotonin uptake and concentration in major depressive disorder.

In an open study of 12 inpatients who met the DSM-III criteria for a major depressive episode, the effects of clomipramine (CI) on the monoamine metabolites 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), 4-hydroxy-3-methoxyphenyl glycol (HMPG) in cerebrospinal fluid (CSF) were measured simultaneously with the effects on 3H-imipramine binding, serotonin (5-HT) uptake and 5-HT concentration in platelets after 3 and 6 weeks of treatment. Drug (CI and desmethylclomipramine) plasma concentrations were determined. The concentrations of 5-HIAA and HMPG decreased substantially, and the concentration of HVA remained unchanged. There was also a large and significant reduction of the number of imipramine binding sites (Bmax) and of the platelet 5-HT concentration. The 5-HT uptake was not measurable after 3 weeks of treatment. None of the parameters changed significantly between weeks 3 and 6. There were no significant correlations between antidepressant effect (measured by the Montgomery-Asberg Depression Rating Scale) and plasma drug concentrations, although a tendency to a significant correlation between antidepressant effect and CI was observed at 3 weeks. There were no significant intercorrelations between the different 5-HT parameters and no other significant correlations between the biochemical measures and clinical outcome.     

The influence of age, height, and body weight on cerebrospinal fluid amine metabolites and tryptophan in women

Cerebrospinal fluid 5-hydroxyindoleacetic acid (CSF 5HIAA), homovanillic acid, and tryptophan were measured in 33 depressed, 36 alcoholic, and 32 neurological control female patients selected by strict operational criteria and investigated under controlled circumstances. Plasma total tryptophan was also measured in blood samples taken simultaneously with lumbar punctures. A multivariate regression analysis was done to discover the effect of age, height, and body weight on these four biochemical measures. Only CSF 5HIAA was significantly dependent on the nonspecific patient variables: height, but neither age nor weight, accounted for more than 10% of the variance of 5HIAA. The same analysis was carried out in all three separate patient groups: the relationship between height and CSF 5HIAA was present throughout, and only 2 of 12 correlations proved to be non-homogeneous. To demonstrate the significantly of these clinical parameters a multivariate analysis of covariance was done to eliminate their effect on the four biochemical variables. As a result significant differences emerged in CSF 5HIAA and total plasma tryptophan for some of the patient groups which were not demonstrable without this correction.     

Biochemical investigations into the alcoholic delirium: Alterations of biogenic amines

Summary In eight male patients with alcoholic delirium concentrations of 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovannilic acid (HVA) in CSF, activity of dopamine--hydroxylase (DBH), and urinary excretion of noradrenaline (NA), adrenaline (A), and dopamine (DA) were measured during the delirium and a drug-free control period.MHPG concentration in CSF, excretion of NA and A as well as activity of serum DBH were significantly elevated during the delirium phase as compared to the control period. Urinary DA excretion and HVA in CSF did not show any constant changes. There was a positive correlation (r=0.64) between DBH activity and the intensity of the delirium (as measured on the delirium rating scale).It is hypothesized that there is a relationship between alcoholic delirium and increased central noradrenergic activity.Parts of this study were presented at the Sixth International Institute on the Prevention and treatment of Drug Dependence (Hamburg, June 28–July 2, 1976)     

Correlates of lithium response in psychotic-affective syndromes

We examined clinical and biochemical predictors of lithium response in 17 schizoaffective patients as well as the effect of lithium treatment upon several aminergic systems in this group. Ten patients were rated improved by the addition of lithium to the treatment regimen. No clinical predictors reached significance although DSM-III diagnosis and family history showed trends. Pretreatment plasma GABA was higher in the responders to lithium as compared to the nonresponders. Lithium tended to increase CSF HVA, CSF GABA, and plasma cAMP and to decrease plasma GABA. Lithium had little effect upon CSF 5HIAA, CSF cAMP, or plasma 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.     

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.     

Biogenic amine metabolites and thiamine in cerebrospinal fluid in heredo-degenerative ataxias

BACKGROUND: The aims of the present study were: i) to measure levels of the dopamine metabolite homovanillic acid (HVA), the serotonin metabolite 5-hydroxindoleacetic acid (5HIAA) and precursor tryptophan, as well as the noradrenaline metabolite 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) and thiamine in the cerebrospinal fluid (CSF) of patients with Friedreich's ataxia (FA), olivopontocerebellar atrophy (OPCA), and the autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSAC), as compared with sex- and age-matched control subjects. PATIENTS AND METHODS: CSF amine related compound levels and thiamine results were compared in 40 FA, 44 OPCA and nine ARSAC patients with those of 94 sex- and age-matched subjects. Neuroimaging (CT scans and single photon emission computed tomographies i.e. SPECT) were carried out in all patients and controls. Genetic studies were conducted on OPCA patients. CSF amine related compounds were measured by high performance liquid chromatography, whereas CSF thiamine levels were measured by a microbiological method. RESULTS: FA patients had significantly lower CSF HVA, 5HIAA and thiamine values than control patients and a trend for lower MHPG levels. In OPCA patients, CSF HVA, MHPG and thiamine values were markedly lower whereas CSF 5HIAA values showed only a trend towards lower levels; in ARSAC patients only thiamine and HVA CSF values were lower than those in control subjects. CONCLUSION: After presenting the relationships between neurochemical findings on one side, the degree of ataxia, the degree of cerebellar atrophy and the SPECT findings on the other, the authors concluded that replacement and neuroprotective clinical trials in these patients would have to include two or three drugs because the neurotransmitter deficiencies are multiple.     

Interacting neurotransmitter systems. A non-experimental approach to the 5HIAA-HVA correlation in human CSF

The repeatedly observed strong positive correlation between 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA) in human cerebrospinal fluid (CSF) prompted an investigation to see if conclusions concerning possible interactions between brain serotonin and dopamine turnover could be reached from human CSF concentrations of these acid metabolites. CSF data from patients with depressive disorders diagnosed according to the RDC from Sweden (n = 140) and from the National Institute of Mental Health (n = 35) were used to test structural hypotheses by two statistical approaches--LISREL analysis and logistic regression. Results from both men and women were unequivocal: 5HIAA "controls" HVA, interpretable as a regulatory action of serotonin turnover on dopamine turnover. In women, only 5HIAA was affected by age, height and body size (higher in elderly, short and stout women); no similar relationships were seen in males. The concept of a serotonergic regulation of dopamine turnover was tested on brain punch analyses of serotonin and dopamine and their metabolites in two sets of dogs in a large number of brain areas. Results confirm a facilatory effect of serotonin on indices of dopamine turnover in many brain regions, especially brain stem and hypothalamus. The animal data validate the data analytic approach in humans.     

Multivariate analysis of monoamine indices in patients with chronic schizophrenia

Levels of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), noradrenaline (NA), 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid and serum levels of prolactin (PRL) and dopamine-beta-hydroxylase (DBH) were measured in 42 chronic schizophrenic inpatients grouped according to their scores on the Brief Psychiatric Rating Scale (BPRS) and the Abnormal Involuntary Movement Scale (AIMS). Factor analysis was carried out on various combinations of variables. In patients with tardive dyskinesia (TD), cerebrospinal fluid DA, DOPAC, HVA, NA, and serum DBH were distributed into three factors; in patients without TD, these substances were assembled in only one factor. Cerebrospinal fluid DA, DOPAC, and HVA were dispersed in two factors in patients with severe positive symptoms versus one factor in subjects with mild productive signs. Factor structures diverged only when the variables listed above were included in the analysis. These findings support the hypothesis that both the dopaminergic and the noradrenergic system contribute to TD and that positive schizophrenic symptoms are associated with dopaminergic dysregulation.