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Cerebrospinal metabolites were measured in 17 patients with borderline personality disorder and 17 normal controls. There were no significant differences between the two groups in levels of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), or 3-methoxy-4-hydroxyphenylglycol (MHPG). Within the borderline group, lower levels of CSF 5-HIAA were significantly associated with a history of genuine suicide attempts, but were not associated with violence, self-mutilation, or with the presence of major depression. Thus, CSF 5-HIAA levels are not distinctively low in a diagnostic group characterized by impulsivity and suicidal behavior, but within that group may be associated with genuine suicide attempts.

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.

The metabolites of dopamine (homovanillic acid-HVA), noradrenaline (4-hydroxy-3-methoxy-phenylglycol-HMPG), and serotonin (5-hydroxyindoleacetic acid-5-HIAA) were measured in cerebrospinal fluid (CSF) from 38 patients and urine from 36 patients with typical Rett syndrome (RS) and compared with controls of similar age. CSF metabolite concentrations were the same in the patients and controls. Urinary metabolites expressed per mol creatinine were significantly higher in older RS patients. This difference is partly explained by lower urinary creatinine levels in older RS patients, due to their known reduction in muscle mass. Alterations in CSF or urine biogenic amine metabolite concentrations do not appear to represent the primary abnormality in RS, and their measurement cannot be regarded as a reliable means of diagnosis.

Four monoamine metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylglycol (MHPG) and 5-hydroxyindoleacetic acid (5-HIAA), were determined in the cerebrospinal fluid (CSF) of cadavers, whose causes of death had been suicidal hanging (SH) or ischemic heart failure (IHF). The concentration of DOPAC increased in parallel with the increment of the postmortem interval (PMI) (r = 0.626), whereas the concentrations of HVA, MHPG and 5-HIAA did not. The correlation coefficient was further increased by considering each cause of death separately: i.e., SH, r = 0.761; IHF, r = 0.705. These findings suggest the possible usefulness of the DOPAC level in CSF for estimating PMI.

Adult coeliac patients taking a gluten-free diet for one year showed an increase of 33% in the concentrations in CSF of major monoamine metabolites (5-HIAA, HVA and MOPEG). Tryptophan in CSF rose by 10%. There was concomitant morphological improvement in the jejunal mucosa, and the results would seem to indicate that the reduced central monoamine metabolism in untreated adult coeliacs is not primarily genetically determined but is probably related to the poor intestinal absorption.

We studied 99 hospitalized depressed, 14 manic, and 61 healthy control subjects and evaluated relationships during a drug-free baseline period between behavioral measures (postulated to be associated with brain norepinephrine, dopamine, and serotonin function) and metabolites of these neurotransmitters sampled from lumbar cerebrospinal fluid (CSF): 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid, and 5-hydroxyindoleacetic acid. Depressed subjects with increased anxiety, agitation, somatization, and sleep disturbance were found to have significantly elevated concentrations of CSF MHPG; this relationship was not found in the healthy controls. A correlation between CSF MHPG level and an anxiety/agitation dimension measured in all subjects was statistically significant but explained a modest portion of the total variance. No consistent relationships were found between CSF MHPG and depression/retardation, hostility/interpersonal sensitivity, and global severity, nor did any of these measures correlate significantly with the levels of the other monoamine metabolites, although some trends were found. Other factors did not account for the relationships between CSF MHPG and some behavioral measures, including diagnostic subgroup, motor movement, age, sex, and premenopausal or postmenopausal status in women. Suggested relationships among drug treatment modality, eventual treatment outcome, behavioral and mood state at baseline, and these metabolite levels will require further analyses.

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.

Levels of the amine metabolites homovanillic acid (HVA) and methoxyhydroxyphenylglycol (MHPG) were measured in the cerebrospinal (CSF) fluid of drug-free patients with Alzheimer's disease and compared to levels in a group of controls. No significant differences were found in CSF HVA and MHPG, although the Alzheimer's group was severely demented. Platelet monoamine oxidase (MAO) enzyme kinetics were measured and did not differ between controls and Alzheimer patients. The degree of dementia did not show any significant correlation with the levels of HVA or MHPG. It was concluded that, unlike previous reports in the literature, the dementia of Alzheimer's disease was not related to changes in central catecholamine metabolism nor was it associated with increased platelet MAO activity.

The alpha 2-antagonist idazoxan was administered intravenously to rabbits. The increase in central noradrenergic, dopaminergic and serotonergic activity was followed as a function of time by determining neuronal parameters in the cerebrospinal fluid (CSF) and was compared with changes previously determined after yohimbine. These parameters include the enzyme dopamine-beta-hydroxylase (D beta H), the noradrenergic metabolites 3-methoxy-4-hydroxyphenylmandelic acid (VMA) and 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), the dopaminergic metabolite 3-methoxy-4-hydroxyphenylacetic acid (HVA) and the serotonergic metabolite 5-hydroxyindole acetic acid (5-HIAA). Control experiments with physiological saline were also performed. D beta H activity increased to 211% in control experiments, and to 570 and 530%, respectively after yohimbine and idazoxan. Compared to the control experiments yohimbine was able to elevate VMA, MHPG and HVA concentrations, but 5-HIAA levels were reduced. Idazoxan caused increased MHPG concentrations, slight increases in VMA, little effect on HVA and no effect on 5-HIAA levels. We conclude that idazoxan was as potent as yohimbine as an alpha 2-antagonist in our in vivo experiments and that idazoxan shows a much greater selectivity with regard to the noradrenergic system.

The effects of alpha 2-adrenoceptor agonists on the concentrations of monoamine metabolites in cisternal cerebrospinal fluid (CSF) of freely moving rats were determined. Clonidine and two new imidazole derivatives, detomidine and medetomidine, and diazepam (as a control substance) were administered in sedative doses and the concentrations of unconjugated 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) in CSF were monitored for 48 h. The alpha 2-agonists caused a dose-dependent, statistically significant decrease in the concentration of MHPG in CSF compared to the concentration in animals treated with saline or diazepam. Detomidine caused a statistically significant increase in the concentration of 5-HIAA compared to control treatments. The present results demonstrate the usefulness of monitoring drug-induced alterations in central nervous system (CNS) noradrenergic activity by measuring free MHPG in repeatedly collected cisternal CSF samples from freely moving rats. The alpha 2-agonists reduced the concentration of MHPG in CSF, indicating a decreased release, metabolism and turnover of noradrenaline in the CNS.

In order to study the role of the neurotransmitter noradrenaline (NA) and its main brain metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) in autonomic failure in Parkinson's disease (PD), an analysis of the relation of cerebrospinal fluid (CSF) NA and MHPG levels and a rating of autonomic nervous system (ANS) impairment was carried out. The mean baseline NA level in CSF of PD patients was 220.0 +/- 110.0 pg/ml, and the mean baseline MHPG level 9.9 +/- 3.9 ng/ml. These levels did not differ from those of age-matched controls. Within the group of patients with PD neither the duration of the disease nor its medication influenced the results. No correlation could be found in patients with PD between the CSF NA levels and the severity of autonomic failure, but a clear correlation was found between the CSF MHPG concentrations and the severity of autonomic failure.

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.

In order to understand the role of monoamines in cerebral ischemia, 3-methoxy-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.

Cerebrospinal fluid was collected from the lateral ventricles and cisternal space from beagle dogs under light pentobarbital anesthesia. Homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglyco-sulfate (MOPEG-SO4) levels in the liquor taken from these two regions were evaluated, and the ventricular-cisternal ratio (V/C) was calculated for each monoamine metabolite. A marked similarity in the V/C ratio of 6:1 for 5-HIAA and 5:1 for MOPEG-SO4, as compared to a much higher V/C ratio of 18:1 for HVA, perhaps reflects the more diffuse distribution of norepinephrine and serotonin, precursor amines, as compared to dopamine in the CNS and also emphasizes the probable existence of an active transport mechanism for the removal of MOPEG-SO4, as has been well documented for 5-HIAA and HVA.

In 28 patients with primary depression, relationships were sought between rating scores on the Montgomery-Asberg Depression Rating Scale and the concentrations of the monoamine metabolites 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and 4-hydroxy-3-methoxyphenylglycol (HMPG) in cerebrospinal fluid (CSF). Among the single items in the rating scale, reported sadness correlated negatively with HMPG. No other significant relationships were found in the total group of patients. However, in subgroups with low or high concentrations of monoamine metabolites, several significant relationships were found, such as a negative correlation between inner tension and concentration difficulties, respectively, and 5-HIAA in the low-HMPG subgroup. Curvilinear relationships were found between pessimistic thoughts and 5-HIAA in the high-5-HIAA subgroup and between apparent sadness and 5-HIAA in the low-HMPG subgroup. Suicidal thoughts tended to correlate in a curvilinear way with the ratio of HMPG/5-HIAA in the low-HVA and the high-HMPG subgroups, but the curves were mirrored. The results indicate that relationships between clinical symptoms and monoamine metabolite homeostasis in CSF are qualitatively and quantitatively different in defined high-and low-monoamine subgroups of depressed patients.

Memory performance, central monoaminergic function and sympathetic nerve activity were studied in patients with dementia of the Alzheimer type (DAT) or with multi-infarct dementia before and after 4 weeks with single or combined drug therapy (choline-piracetam). Analysis of the levels of 3-methoxy-4-hydroxyphenylglycol (MHPG), 3-methoxy-4-hydroxyphenylacetic acid (HVA) and 5-hydroxyindolacetic acid in the cerebrospinal fluid (CSF) and also in urine (plus 3-methoxy-4-hydroxy mandelic acid) showed that the basal values of HVA in the CSF and urine were lower in the more severely demented compared with the mildly demented subjects in both groups. The combined drug treatment resulted in a statistically significant increase in the MHPG level in the CSF of mildly demented subjects of the DAT group, while it seemed not to influence the other monoamine metabolites. The sympathetic nerve activity was similar in both patient groups and was unchanged after therapy. These findings suggest a dopaminergic deficit in advanced stages of the disease and a possible enhancement of the central noradrenergic output with therapy. No effects of therapy on memory performance or correlations between monoamine levels and memory test scores were noted.

Concentrations of free 3-methoxy-4-hydroxyphenylglycol in the plasma and cerebrospinal fluid are highly correlated, but concentrations in the cerebrospinal fluid are always higher than those in plasma, even when large amounts of the catecholamine metabolite are derived from a tumor of the adrenal medulla. This is explained by considering the plasma and cerebrospinal fluid as a two-compartment system in which the rate constants for entry into and exit from the cerebrospinal fluid compartment are similar. 3-Methoxy-4-hydroxyphenylglycol that is synthesized, but not catabolized, in the central nervous system maintains cerebrospinal fluid levels at an increment over those in plasma. This increment can be used to provide the best available index of formation of 3-methoxy-4-hydroxyphenylglycol in the central nervous system.

We measured CSF and plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) in patients with orthostatic hypotension. Total CSF MHPG levels were significantly lower than normal in patients with either multiple system atrophy (MSA) or idiopathic orthostatic hypotension (IOH). Only IOH patients had low plasma levels of MHPG. Correction of CSF MHPG levels for the contribution from plasma free MHPG provides an index of central norepinephrine metabolism. In MSA, abnormal function of central noradrenergic pathways seems to cause the low CSF MHPG levels. In IOH, the decreased CSF MHPG results from the diminished plasma MHPG levels.

Descending bulbospinal pathways that employ specific neurotransmitter substances are known to be capable of modulating segmental reflex activity in the experimental animal. To determine whether this might also occur in man correlations have been sought between the activity in spinal reflex pathways and the lumbar cerebrospinal fluid (CSF) concentrations of 5-hydroxyindolacetic acid (5-HIAA), 3 methoxy-4-hydroxyphenylglycol (MHPG), and homovanillic acid (HVA) in 12 patients with complete or virtually complete spinal lesions. The concentrations of 5-HIAA and MHPG in lumbar CSF ARE REDUCED AFTER COMPLETE OR VIRTUALLY COMPLETE SPINAL LESIONS IN MAN. This may occur within 18 days of the lesion. MHPG concentrations appear to be inversely related to the level of the lesion. The HVA concentration in lumbar CSF is reduced when there is obstruction of the CSF pathways. No relationship could be demonstrated between the concentrations of 5-HIAA or MHPG in lumbar CSF and the activity in the spinal monosynaptic pathway (estimated from the proportion of the motoneurone pool activated by the Achilles tendon reflex or H reflex) or the activity of a spinal inhibitory mechanism (estimated by the degree of vibratory inhibition of the monosynaptic reflex). Patients with a tonic vibration reflex (TVR) tended to have higher MHPG levels. There appeared to be an association between low CSF HVA and enhanced vibratory inhibition of the monosynaptic reflex in the nine patients whose spinal lesions were complete.

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.

The monamine metabolites 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), vanillylmandelic acid (VMA), and 4-hydroxy-3-methoxyphenylglycol (HMPG) were analysed in CSF from different regions of the CSF system to study the caudocranial concentration gradient of the metabolites. Four consecutive 10 ml fractions of CSF were withdrawn in 17 patients during the course of four minutes. The CSF pressure was monitored through a lumbar cannula because of suspected adult hydrocephalus. A pronounced gradient of the HVA concentration was found with a ratio between the last and the first fraction of 1,7. 5-HIAA showed a slight increase while HMPG and VMA showed no increase at higher levels of the CSF system. The results suggest that lumbar HVA reflects dopaminergic activity in the brain, whereas lumbar 5-HIAA and HMPG/VMA reflect the activity of 5-hydroxytryptamine and noradrenaline secreting neurones in both the brain and the spinal cord.

Concentrations of 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) were measured in human lumbar cerebrospinal fluid following storage at room temperature and 4 degrees C for intervals up to 72 hours. These monoamine metabolites were quantitated using a high-performance liquid chromatographic-electrochemical detector technique. No significant difference could be detected in any of the three metabolites stored at room temperature for up to 48 hours. Addition of ascorbic acid to CSF had no measurable effect on the levels of HVA and 5-HIAA. Repeated thawing and freezing produced no detectable change in metabolite levels. The results indicate that these monoamine metabolites are stable at room temperature for up to 48 hours after lumbar puncture and that the addition of an antioxidant, such as ascorbic acid, is not necessary. The data also demonstrate that immediate refrigeration or freezing of samples is not required for maintenance of metabolite levels.

The concentrations of homovanillic acid (HVA), 3-methoxy, 4-hydroxyphenylglycol (MHPG), and 5-hydroxyindolylacetic acid (5-HIAA) were measured in samples of ventricular cerebrospinal fluid (CSF) taken from 15 patients who were comatose as a result of an acute head injury, a tumour, or a cerebrovascular accident. The metabolite levels were not related to the ventricular fluid pressure. In the eight patients who recovered and from whom serial samples of CSF were obtained, the metabolite levels did not change, except for two patients in whom HVA increased as coma progressed. The concentration of MHPG, but not of HVA or 5-HIAA, was greater (P less than 0.02) in the five patients who died without regaining consciousness than in the 10 patients who recovered.

Baseline concentrations of beta-endorphin (beta-EP) and monoamine metabolites (MHPG: 3-methoxy-4-hydroxy-phenylglycol, HVA: homovanillic acid, 5-HIAA: 5-hydroxyindoleacetic acid) in lumbar CSF (LCSF) and ventricular CSF (VCSF) were measured in 18 patients with intractable pain; 10 with deafferented pain and 8 with peripheral pain. Control values were obtained from 37 individuals of various ages. Changes in the concentrations of these substances were determined before and after giving stimulations (2-5 V, 0.2-0.5 msec, 40-50 Hz, 20-sec duration) to 6 patients through electrodes implanted in deep brain structures (DBS; posterior limb of the internal capsule in 5 patients and rostral mesencephalic lemniscus medialis in one patient), and to 2 other patients through electrodes implanted in the spinal dorsal column (DCS). The control value of beta-EP in LCSF was 57.6 +/- 24.7 pg/ml, which was not significantly different from that of VCSF. Great variation in the individual control LCSF beta-EP concentrations was found, but it was not related to differences in age. The mean baseline LCSF beta-EP concentration was significantly higher (p less than 0.05) than the control in the patients with deaffernted pain before stimulation. One of the monoamine-metabolites, MHPG, showed higher level in the patients with peripheral pain (p less than 0.01). The LCSF beta-EP concentration was not affected by deep brain stimulation, but was increased by dorsal column stimulation. In one patient with excellent pain relief by stimulation of the posterior limb of the internal capsule, the LCSF HVA and 5-HIAA concentrations were conspicuously increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebrospinal (CSF) fluid content of the stable metabolites homovanillic acid, 3-methoxy-4-hydroxyphenyl glycol and 5-hydroxyindoleacetic acid were measured in 19 children without neurological disease known to alter CSF monoamine metabolites. The CSF levels of all three metabolites were found to be up 6 times higher in early infancy compared to the values during adolescence. The levels decreased in a logarithmic fashion, and adult values (approx. 25-50 ng/ml) were reached at 3-5 years of age. Two different interpretations of the findings are discussed: (1) a higher release or turnover of central serotonin and catecholamine metabolites during early postnatal age, or (2) lower clearance of the stable acid metabolites from CSF during infancy due to relatively immature active transport mechanisms.

Cerebrospinal fluid levels of homovanillic acid (HVA) in unmedicated patients with Parkinson's disease were 45% of levels in control subjects. Levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) and platelet monoamine oxidase activity (MAO) did not differ. Within the Parkinson's disease group platelet MAO B activity correlated with HVA (an MAO B substrate) but not MHPG (an MAO A substrate). A mild global dementia was found that did not correlate with the more severe motor deficit. There was a negative correlation between the motor deficit and HVA levels but not with MHPG. Cognitive functioning correlated positively with platelet MAO, and the ratio of HVA to MHPG levels and negatively with MHPG alone. It is postulated that dopaminergic and noradrenergic activity or the functional balance between these systems may contribute to the observed cognitive dysfunction.

The concentrations of homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), 4-hydroxy-3-methoxyphenylglycol (HMPG), and glutamate were determined in cerebrospinal fluid (CSF) and serum in 10 healthy volunteers. The monoamine metabolites were measured by mass fragmentography and the glutamate by high-performance liquid chromatography. The level of glutamate in CSF was low (0.34 +/- 0.14 nmol/ml) in comparison with previously published values. The concentrations of monoamine metabolites in CSF were in close agreement with earlier findings. There were negative correlations between the concentrations of HVA (r = -0.82, p less than 0.01) and 5-HIAA (r = -0.77, p less than 0.01) and glutamate in CSF, but not in serum. The serum levels of HMPG and glutamate were negatively correlated (r = -0.95, p less than 0.001), but not the CSF levels. The HMPG levels in serum and CSF were positively correlated (r = 0.94, p less than 0.001), but not the HVA and the 5-HIAA levels. The serum and CSF levels of glutamate were positively correlated (r = 0.67, p less than 0.05). The results indicate relationships among the metabolism of dopamine, serotonin, and glutamate in the brain and between the metabolism of noradrenaline and glutamate in peripheral tissue.

Korsakoff's psychosis is associated with impairments of memory and perception but not global dementia. We have previously reported diminished concentrations of catecholamine metabolites in the CSF of patients with Korsakoff's psychosis. In this study, we compared CSF monoamine metabolite data with performance on psychometric tests for 26 patients with this disease. We report that patients with more severe neurobehavioral deficits have lower concentrations of monoamine metabolites. Our data also provide evidence that diminished brain noradrenergic and dopaminergic activities are related to impairments on different psychometric tasks.

The concentrations of the dopamine metabolite homovanillic acid (HVA), the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) and the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MOPEG) were determined in cerebrospinal fluid (CSF) from patients with subarachnoid haemorrhage (SAH) using a mass fragmentographic method. In a first group of 24 patients lumbar CSF was collected during the first 10 days after SAH. The concentrations of HVA and 5-HIAA showed a several-fold increase in the majority of subjects while that for MOPEG was less pronounced in comparison to controls. In a second group of 12 SAH-patients, CSF was collected in 10 ml fractions during surgical clipping of aneurysms. The mean concentrations of HVA, 5-HIAA and MOPEG in lumbar CSF was 469,275 and 39 pmol/l, respectively, whereas central CSF concentrations were 1,212, 499 and 48 pmol/ml, respectively. Compared to healthy controls, both HVA and 5-HIAA showed increased levels (pl 0,01) but MOPEG was within the normal range. No correlation between the concentrations of the monoamine metabolites, the neurological condition or the cerebral vascular diameter was observed in neither of the two groups. It is suggested that the accumulation of HVA and 5-HIAA in SAH patients is explained by a disturbance of the active transport mechanism.

Clinical studies of monoamine neurotransmitter function in depression have concentrated on individual monoamines without focusing on interactions between monoamine systems. Virtually all modern studies have found significant correlations between monoamine metabolite concentrations in cerebrospinal fluid (CSF). These correlations should in part reflect interactions between central monoamine systems. In the present analysis, CSF had been obtained from depressed patients before (n = 40) and after (n = 36) antidepressant treatment. The patients were grouped based on their response to treatment. Absolute concentrations of CSF monoamine metabolites (homovanillic acid, 5-hydroxyindoleacetic acid, and 3-methoxy-4-hydroxyphenylethyleneglycol) did not differ between the two groups before or after treatment. However, when correlations between metabolites were compared, nonresponders to treatment differed considerably from responders. In responders, as in previously described normal populations, all three metabolites correlated with one another before and after treatment, and treatment-induced changes in metabolite concentrations also correlated with one another. In contrast, metabolites in nonresponders did not correlate with one another before treatment, nor did treatment-induced changes correlate with one another in this group. Furthermore, correlations between treatment-induced changes in metabolites differed significantly between responders and nonresponders, and there was a trend for pretreatment correlations to differ as well. The lack of correlation between monoamine metabolites in nonresponders suggests that interactions between monoamine systems may be disrupted in these individuals. Using CSF metabolite correlations to study neurotransmitter interactions may have clinical relevance and yields information not available from examining neurotransmitters in isolation.

The concentrations of arginine vasopressin (AVP), somatostatin (SS), and the primary brain metabolites of norepinephrine (MHPG), serotonin (5-HIAA), and dopamine (HVA) were measured in samples of lumbar CSF obtained from ten amnesics with Korsakoff's psychosis, four patients with a history of Korsakoff's psychosis who had recovered from the amnesic symptoms of this disease, and control subjects. Significant deficits were observed in the amnesic group for AVP and MHPG, but not for the other substances measured. Subjects who had recovered from the amnesic symptoms of Korsakoff's psychosis had increased concentrations of AVP and MHPG, but not of SS or the other monoamine metabolites.

The effect of ECT on concentrations of monoamine metabolites in lumbar CSF of psychotic women with a schizophrenic symptomatology was examined. After a series of ECT there was a significant reduction of the concentration of the major noradrenaline metabolite, MOPEG. Levels of HVA, 5-HIAA, prolactin, or total protein in CSF were not significantly influenced by treatment. The results indicate a specific alteration of central noradrenaline metabolism in relation to ECT.

Cerebrospinal fluid (CSF) homovanillic acid, 5-hydroxyindoleacetic acid, 3-methoxy-4-hydroxyphenylglycol, and somatostatin and beta-endorphin levels were measured in 12 patients with panic disorder before and after 7 months of treatment with alprazolam or imipramine. The concentrations of CSF monoamine metabolites and neuropeptides were at baseline of the same order of magnitude in panic patients and controls. Neither alprazolam nor imipramine changed metabolite or neuropeptide levels in CSF despite clinical improvement in both treatment groups. According to present CSF data, the antipanic actions of alprazolam and imipramine do not involve the monoaminergic or peptidergic systems studied.

Determination of monoamine metabolites was accomplished in the spinal fluid of 22 psychotic children and in 22 sex- and almost-age-matched "normal" controls. Also, specimens from groups of mentally retarded children and children with progressive encephalopathy or meningitis were used for comparison. The psychotic children showed raised levels of homovanillic acid. Thirteen children diagnosed as autistic by Rutter's criteria showed isolated increase of this metabolite. In the group of 9 children with other psychoses, both the level of homovanillic acid and that of 5-hydroxy-indoleacetic acid was raised. The comparison with the group of "simply" mentally retarded children and results within the psychotic group revealed that the increased concentration of monoamines was not attributable to mental retardation per se.

To assess the possible role of amine neurotransmitters in human epilepsy, we measured metabolites of serotonin (5-hydroxyindoleacetic acid [5-HIAA]), dopamine (homovanillic acid [HVA]), and norepinephrine (3-methoxy-4-hydroxyphenylethylene glycol [MHPG]) in the lumbar cerebrospinal fluid (CSF) of patients with partial complex seizures and in neurologic controls. Untreated epileptic patients had lower concentrations of 5-HIAA and HVA in the lumbar CSF than the controls, but the differences were not statistically significant. Among epileptic patients receiving effective antiepileptic drug treatment, the HVA concentration was within the control range. Mean MHPG concentrations were similar in patients and controls. From the epileptic patients whose CSF was obtained at pneumoencephalography we obtained a second sample of CSF that was originally in the basal cisterns. No significant differences between treated and untreated patients were found for any of the three metabolites. The concentrations of HVA and 5-HIAA were higher in cisternal than in lumbar CSF, but there was no such gradient for MHPG.

Patients with Alzheimer disease (AD, onset less than 65 years of age, n = 13) and senile dementia of the Alzheimer type (SDAT, onset greater than or equal to 65 years of age, n = 28) were investigated for cerebrospinal fluid (CSF) content of homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-4-hydroxy-phenylglycol (MHPG) and compared with a group of controls (n = 26). A geriatric rating scale, the Gottfries-Bråne-Steen scale, was used to assess impairment of motor performance, intellectual and emotional functioning, and symptoms common in dementia disorders. The HVA levels in CSF were significantly lower in the AD group than in the SDAT group and controls. MHPG was slightly but significantly increased in the SDAT group when compared with the controls. The HVA and 5-HIAA concentrations were correlated negatively with impairment of motor performance in the SDAT group; 5-HIAA correlated positively with impaired performance in the AD group; and 5-HIAA/HVA ratios were correlated positively with the performance variables. HVA correlated significantly and negatively with "impaired wakefulness" and "inability to increase tempo" in the SDAT group. 5-HIAA and the ratio 5-HIAA/HVA correlated significantly and positively with some items measuring intellectual and emotional impairment. In the AD group, "anxiety" and "fear-panic" correlated positively with 5-HIAA and "restlessness" with MHPG. The data indicate qualitative differences in the CSF monoamine pattern between AD and SDAT.

Main monoamine metabolities of cerebrospinal fluid (CSF), i.e., 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), were measured in 74 patients with neurodegenerative diseases, in 30 normal control subjects and in 16 diseased control subjects without neurodegenerative diseases. The symptoms of patients were scored according to an original scale. It was suggested by statistical study including multiple regression analysis that there might be significant relationship between CSF-MHPG level and extrapyramidal symptoms, or autonomic symptoms, and between CSF-5-HIAA level and extrapyramidal, or cerebellar symptoms, and between CSF-HVA level and extrapyramidal, pyramidal, or cerebellar symptoms. It was also suggested that the severer the symptoms of patients with Parkinson's disease, Shy-Drager syndrome, or olivopontocerebellar atrophy became, the lower the levels of monoamine metabolities of CSF became. The activity of peripheral catecholamine metabolism might influence the CSF-MHPG level because of the significant positive correlations between CSF-MHPG level and urine noradrenaline or vanillylmandellic acid level. The level of MHPG was high in patients with severe amyotrophic lateral sclerosis or hereditary spinocerebellar degeneration possibly because of stress with respiratory dysfunction.

This prospective study included 32 patients with primary hyperparathyroidism (HPT). As compared with a healthy reference group, the patients had pronounced psychiatric symptomatology [CPRS score 17.2 +/- 9.0 (SD) versus 4.4 +/- 2.0], which was mainly affective in character. The severity of symptoms was not related to the serum calcium or parathyroid hormone concentrations. The majority of the patients had low CSF concentrations of monoamine metabolites (5-HIAA, HVA, and MHPG) and, in particular, those with the most severe psychiatric symptoms had low values for 5-HIAA. At follow-up, 1 year after parathyroid surgery, the patients displayed a clear improvement in mental health (CPRS score 4.4 +/- 3.0) together with an increase in CSF concentrations of 5-HIAA and HVA. The study demonstrates that significant psychiatric disturbances, which can be improved/normalized by surgery, are common in patients with HPT and are possibly related to changes in the central nervous system turnover of monoamines.

Rabbits were treated intravenously with yohimbine at a dose of 5 mg/kg. The concomitant increase in noradrenergic activity was followed in function of time by measuring dopamine-beta-hydroxylase activity and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) and 3-methoxy-4-hydroxymandelic acid (VMA) levels in cerebrospinal fluid. In addition, the effect of yohimbine on the dopaminergic, serotonergic and enkephalinergic neurotransmission was also determined. For this purpose, the dopamine metabolite, 3-methoxy-4-hydroxyphenylacetic acid (HVA), the serotonin metabolite, 5-hydroxy-indole acetic acid (5-HIAA) and methionine-enkephalin (Met-Enk) were quantified. The D beta H activity in control experiments, in which physiological saline was administered, increased up to 200% whereas in the yohimbine experiments a rise to 500-600% was observed. VMA and MHPG levels increased to 290%, and 209% respectively. HVA levels reached a value of 233% versus the concentration before drug injection, whereas 5-HIAA concentrations initially slightly increased and thereafter decreased. In the corresponding control experiments metabolite concentrations were virtually stable. Following yohimbine injection, methionine-enkephalin concentrations did not show significant variations compared with the control experiments. We conclude that noradrenergic and dopaminergic neurotransmission are increased following administration of the alpha 2-antagonist yohimbine whereas serotonergic neurotransmission is slightly decreased and enkephalinergic neurotransmission is unaltered. The value of the different parameters for measuring neuronal activity in cerebrospinal fluid is discussed.

Psychobiological data on 58 violent offenders and impulsive fire setters were analyzed for associations with history of suicide attempts. Subjects with a history of suicide attempts serious enough to require an admission to a medical facility had significantly lower mean cerebrospinal fluid 5-hydroxyindoleacetic acid and 3-methoxy-4-hydroxyphenylglycol concentrations than subjects who had not made such attempts. A linear discriminant function analysis based on psychobiological and behavioral variables correctly classified 79% of the subjects according to the suicide attempt history positive and negative outcomes.

A female newborn infant with Marfan-like habitus experienced lethargy and hypothermia associated with tyrosinemia that was not corrected by the administration of ascorbic acid at 50 mg/day but that subsequently responded to ascorbic acid at 500 mg/day. Cerebrospinal fluid analysis for neurotransmitter metabolites showed elevated concentrations of homovanillic acid and 5-hydroxyindoleacetic acid when the child was symptomatic and normal concentrations after successful ascrobic acid therapy. These observations suggest that a high level of tyrosine in serum can affect the metabolism in the brain of dopamine and serotonin.

Cerebrospinal fluid (CSF) and plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations were significantly elevated in patients during the alcohol withdrawal syndrome. When CSF MHPG was corrected using a formula proposed to determine CSF MHPG levels of central origin, these values were still significantly elevated when compared with control values. The MHPG concentrations in CSF also showed significant positive correlations with heart rate, systolic and diastolic blood pressures, tremor, anorexia, and sweating. The results of this study indicate increased presynaptic release of norepinephrine during alcohol withdrawal.