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Widely targeted metabolomic assays are useful because they provide quantitative data on large groups of related compounds. We report a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method that utilizes benzoyl chloride labeling for 70 neurologically relevant compounds, including catecholamines, indoleamines, amino acids, polyamines, trace amines, antioxidants, energy compounds, and their metabolites. The method includes neurotransmitters and metabolites found in both vertebrates and insects. This method was applied to analyze microdialysate from rats, human cerebrospinal fluid, human serum, fly tissue homogenate, and fly hemolymph, demonstrating its broad versatility for multiple physiological contexts and model systems. Limits of detection for most assayed compounds were below 10nM, relative standard deviations were below 10%, and carryover was less than 5% for 70 compounds separated in 20min, with a total analysis time of 33min. This broadly applicable method provides robust monitoring of multiple analytes, utilizes small sample sizes, and can be applied to diverse matrices. The assay will be of value for evaluating normal physiological changes in metabolism in neurochemical systems. The results demonstrate the utility of benzoyl chloride labeling with HPLC-MS/MS for widely targeted metabolomics assays., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: The mechanisms of the ketogenic diet remain unclear, but several predictors of response have been proposed. We aimed is to study the relationship between the etiology of epilepsy, cerebrospinal fluid neurotransmitters, pterins, and amino acids, and response to a ketogenic diet., Methods: We studied 60 patients who began classic ketogenic diet treatment for refractory epilepsy. In 24 of 60 individuals, we analyzed cerebrospinal fluid neurotransmitters, pterins, and amino acids in baseline conditions. Mean age at epilepsy onset was 24 months, 83.3% were focal epilepsies, and in 51.7% the etiology of the epilepsy was unknown., Results: Six months after initiating the ketogenic diet, it was effective (greater than a 50% reduction in seizure frequency) in 31.6% of patients. We did not find a link between rate of efficacy for the ketogenic diet and etiologies of epilepsy, nor did we find a link between the rate of efficacy for the ketogenic diet and cerebrospinal fluid pterins and biogenic amines concentrations. However, we found statistically significant differences for lysine and arginine values in the cerebrospinal fluid between ketogenic diet responders and nonresponders, but not for the other amino acids analyzed., Significance: The values of some amino acids were significantly different in relationship with the ketogenic diet efficacy; however, the epilepsy etiology and the cerebrospinal fluid biogenic amine and pterin values were not., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Behavioral and psychological signs and symptoms of dementia (BPSD) are a heterogeneous group of behavioral and psychiatric disturbances occurring in dementia patients of any etiology. Research suggests that altered activities of dopaminergic, serotonergic, (nor)adrenergic, as well as amino acid neurotransmitter systems play a role in the etiopathogenesis of BPSD. In this study we attempted to identify cerebrospinal fluid (CSF) neurochemical correlates of BPSD to provide further insight into its underlying neurochemical pathophysiological mechanisms., Methods: Patients with probable Alzheimer's disease (AD; n = 202), probable AD with cerebrovascular disease (n = 37), probable frontotemporal dementia (FTD; n = 32), and probable dementia with Lewy bodies (DLB; n = 26) underwent behavioral assessment and lumbar puncture. CSF levels of six amino acids and several biogenic amines and metabolites were analyzed using ultraperformance liquid chromatography with fluorescence detection and reversed-phase high-performance liquid chromatography with fluorescence detection., Results: In the AD patients, CSF homovanillic acid/5-hydroxyindoleacetic acid (HVA/5HIAA) ratios correlated positively with anxieties/phobias, whereas CSF levels of taurine correlated negatively with depression and behavioral disturbances in general. In FTD patients, CSF levels of glutamate correlated negatively with verbally agitated behavior. In DLB patients, CSF levels of HVA correlated negatively with hallucinations., Conclusions: Several neurotransmitter systems can be linked to one specific behavioral syndrome depending on the dementia subtype. In addition to biogenic amines and metabolites, amino acids seem to play a major role in the neurochemical etiology of BPSD as well., (Copyright © 2013 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

Neurotransmitter amino acids like Alanine (Ala), Glutamic acid (Glu), Aspartic acid (Asp), Serine (Ser), Taurine (Tau), and Glycine (Gly) are widely distributed in biological fluids and tissues and they have important physiological functions, so that the evaluation of their levels in organisms plays an essential role in physiology. We here report a new capillary electrophoresis (CE) method with laser-induced fluorescence detection by which analytes are resolved and detected in less than 12 min both in human plasma and in other samples types, such as red blood cells, urine, cultured cells, cerebrospinal fluid, saliva, and vitreous humor, thus avoiding the typical limitations of the other methods normally suitable only in one or two matrix types.

The role of neurotransmitter amino acids (NAAs) in the functioning of the nervous system has been the focus of increasingly intense research over the past several years. Among the various amino acids that have important roles as neurotransmitters, there are alanine (Ala), glutamic acid (Glu), aspartic acid (Asp), serine (Ser), taurine (Tau) and glycine (Gly). NAAs are present in plasma, cells and--at trace levels--in all biological fluids, but complex components in biological matrices make it difficult to determine them in biological samples. We describe a new capillary electrophoresis (CE) method with laser-induced fluorescence detection by which analytes are resolved in less than 12 minutes in a 18 mmol/L phosphate run buffer at pH 11.6. The use of elevated temperatures during sample derivatization leads to a drastic reduction in the reaction time, down to 20 min, compared to the 6-14 h usually described for reactions between FITC and amino acids at room temperature. In order to demonstrate its wide range of applications, the method was applied to the analysis of NAA in human plasma and in other sample types, such as red blood cells, urine, cultured cells, cerebrospinal fluid, saliva and vitreous humor, thus avoiding the typical limitations of other methods, which are normally suitable for use with only one or two matrix types.

Anomalies in neuropeptides and neuroactive amino acids have been postulated to play a role in neurodegeneration in a variety of diseases including the inherited neuronal ceroid lipofuscinoses (NCLs, Batten disease). These are often indicated by concentration changes in cerebrospinal fluid (CSF). Here we compare CSF neuropeptide concentrations in patients with the classical juvenile CLN3 form of NCL and the classical late infantile CLN2 form with neuropeptide and neuroactive amino acid concentrations in CSF from sheep with the late infantile variant CLN6 form. A marked disease related increase in CSF concentrations of neuron specific enolase and tau protein was noted in the juvenile CLN3 patients but this was not observed in an advanced CLN2 patient nor CLN6 affected sheep. No changes were noted in S-100b, GFAP or MBP in patients or of S-100b, GFAP or IGF-1 in affected sheep. There were no disease related changes in CSF concentrations of the neuroactive amino acids, aspartate, glutamate, serine, glutamine, glycine, taurine and GABA in these sheep. The changes observed in the CLN3 patients may be progressive markers of neurodegeneration, or of underlying metabolic changes perhaps associated with CLN3 specific changes in neuroactive amino acids, as have been postulated. The lack of changes in the CLN2 and CLN6 subjects indicate that these changes are not shared by the CLN2 or CLN6 forms and changes in CSF concentrations of these compounds are unreliable as biomarkers of neurodegeneration in the NCLs in general.

Objective: To determine concentrations of excitatory and inhibitory amino acids in CSF of a large number of dogs with idiopathic epilepsy or genetic epilepsy and to evaluate changes in CSF amino acid concentration with regard to drug treatment and sex., Animals: 35 Labrador Retrievers with genetic epilepsy (20 male and 15 female), 94 non-Labrador Retrievers with idiopathic epilepsy (71 male and 23 female), and 20 control dogs (10 male and 10 female)., Procedure: Collection of CSF was performed > 72 hours after the occurrence of seizures. Cerebrospinal fluid concentrations of gamma-aminobutyric acid (GABA), glutamate (GLU), aspartate (ASP), serine, and glycine were determined by use of high performance liquid chromatography with electrochemical detection., Results: CSF concentrations of GABA and GLU were significantly lower in Labrador Retrievers with genetic epilepsy (LR-group dogs) than in control-group dogs or in non-Labrador Retrievers with idiopathic epilepsy (non-LR-group dogs). The GLU-to-GABA ratio was significantly higher in LR-group dogs than in non-LR-group dogs. CSF concentrations of GLU and ASP were significantly lower when all dogs with epilepsy (non-LR- and LR-group dogs combined) were compared with control-group dogs., Conclusions and Clinical Relevance: A decrease in CSF concentrations of GABA appears to play a role in the pathogenesis of genetically determined epilepsy in Labrador Retrievers. However, this decrease in CSF concentrations of GABA may also be a consequence of seizure activity. The GLU-to-GABA ratio may prove to be a useful indicator of genetic epilepsy in Labrador Retrievers.

Objectives: Electrophysiological studies of amyotrophic lateral sclerosis (ALS) patients reveal not only lower motor neuron involvement, but also widespread signs of its hyperexcitability. They might be the consequence of changes in the level of amino acids acting as neurotransmitters., Material and Methods: Electrophysiological examination of 31 patients with sporadic ALS was performed. A hyperexcitability index (HI) was created to describe the amount of double discharges, fasciculation potentials or 'giant' F-waves. Glutamate, aspartate, glycine and GABA concentration in serum and cerebrospinal fluid (CSF) were estimated, using the high performance liquid chromatography technique., Results: The electrophysiological studies revealed marked variability in HI in the patients group. HI did not correlate with duration of the disease and the degree of disability expressed with Norris score, as well as with the level of excitatory or inhibitory amino acids in the body fluids., Conclusion: Hyperexcitability of the motor unit observed in ALS is not directly related to changes in serum and CSF level of amino acids acting as neurotransmitters.

Acetylcholinesterase (AChE), choline, monoamine and its metabolite, amino acid and superoxide dismutase (SOD) levels were measured in cerebrospinal fluid (CSF) in patients with cerebrovascular diseases. Patients were classified into the following four groups; controls: normal subjects without neurological disease, group A: cerebral hemorrhage, group B: cerebral infarction, group C: patients with mental impairment, including those in groups A and B, and a low score on Hasegawa's Dementia Rating Scale. CSF AChE level of groups A, B and C was decreased significantly, while choline concentration from patients showed a increase compared with that of control cases. CSF alanine concentration showed a tendency to increase, while glycine and glutamate tended to decrease. CSF epinephrine, norepinephrine or 3-methoxy-4-hydroxyphenylethylen glycol concentrations of groups A, B and C did not exhibit a significant difference from that in control cases. Some cases with cerebrovascular diseases showed low concentrations of both CSF 5-hydroxyindole acetic acid and homovanillic acid. However, dihydroxyphenyl acetic acid concentration was higher than in control cases. The CSF SOD level was not significantly from that in control cases. The changes in neurochemical substances in the CSF support their use as markers of cerebrovascular disease-related change.

Measurement of amino acid levels in the cerebrospinal fluid (CSF) of children with various neurological disorders was performed with high performance liquid chromatography (HPLC). Glutamate increased in patients with bacterial meningitis, aseptic meningitis and encephalitis. Aspartate increased in bacterial meningitis and seizure disorders. Glycine increased in both bacterial and aseptic meningitis. Taurine increased in bacterial meningitis and encephalitis. GABA, the main inhibitory amino acid, increased in encephalitis. Excitatory and inhibitory amino acids are richly distributed in brain tissue and are related to neuron activity. Changes in amino acid levels in the CSF may reflect the pathologic state and severity of brain insults, and may be useful in monitoring disease processes. Further study is necessary to determine whether CSF aminos acid levels have a role in practical clinical application.

We measured the CSF and plasma levels of glutamate, glutamine, aspartate (only in plasma), asparagine, glutamine, glycine and GABA in 31 patients with Parkinson's disease and in 45 matched controls. We used an ion-exchange chromatography method. When compared to controls, PD patients had similar CSF levels of glutamate, glutamine, asparagine, and glycine higher CSF GABA levels higher plasma levels of glutamine, asparagine, and glycine, and lower plasma levels of aspartate. The CSF levels of the amino acids measured were not correlated with the clinical features of PD. Our results that CSF GABA levels are not decreased in PD as previously suggested.

Associations in 52 normal individuals were examined between plasma and cerebrospinal fluid (CSF) concentrations of tryptophan (Trp) and tyrosine, and concentrations of monoamine metabolites in the CSF, and scores on an aggression questionnaire, the Kinsey Institute Reaction List II, and the Eysenck Personality Questionnaire. There was a significantly positive correlation between CSF 5-hydroxyindoleacetic acid (5-HIAA) levels and extroverted aggression scores, and a significantly negative correlation between CSF 5-HIAA levels and introverted aggression scores. Males showed higher plasma Trp concentrations than females, and significantly positive correlations between plasma Trp concentrations and scores on extroverted aggression and the Eysenck E scale. Males, furthermore, showed a significantly negative correlation between CSF Trp levels and scores on the Eysenck P scale, and a significantly positive correlation between concentrations of 3-methoxy-4-hydroxy-phenylglycol in CSF and scores on moral aggression. These results suggest that central serotonin influences aggression in normal individuals through effects on personality.

The concentrations of L-aspartate, L-glutamate, L-serine, glycine and gamma-aminobutyric acid (GABA) were determined in repeated samples of ventricular CSF from five patients with severe closed head injury. The values were compared with those obtained from five subjects undergoing surgical treatment for intractable depression. In the head-injured patients, the concentrations of aspartate, glutamate and glycine were 2- to 8-fold higher and the concentration of GABA 56- to 317-fold higher than control values; the concentration of serine was unaffected. Spearman correlation analysis indicated that the concentration of glutamate significantly increased after injury (Rs = 0.60, p < 0.0001, n = 42), reaching an average concentration of about 7 microM 3 days after the injury. This is probably sufficient to cause further excitotoxicity, which suggests the use of excitatory amino acid receptor antagonists as a treatment following severe head injury may require prolonged administration for maximum therapeutic benefit.

Alterations of brain and cerebrospinal fluid amino acids have consistently been described in human and experimental fulminant liver failure. To evaluate the significance of such changes in the pathogenesis of hepatic encephalopathy in fulminant liver failure, brain and cerebrospinal fluid amino acids (glutamate, aspartate, GABA, glycine, taurine) were measured at various stages during the development of neurological dysfunction in rats after hepatic devascularization or thioacetamide treatment to induce acute liver failure. To facilitate repetitive removal of cerebrospinal fluid, a technique employing long-term implantation of cisterna magna catheters in conscious, freely moving rats was developed. Brain but not cerebrospinal fluid concentrations of the excitatory amino acids glutamate and aspartate were reduced in both animal models of fulminant liver failure in parallel with deterioration of neurological status. Brain and cerebrospinal fluid GABA levels were not significantly altered. Cerebrospinal fluid glycine levels were increased two to three times in parallel with increasing brain glycine content in the devascularized rat but were unchanged in thioacetamide-induced liver failure, suggesting distinct pathophysiological mechanisms in these two experimental situations. On the other hand, onset of coma in both animal models of fulminant liver failure was accompanied by significantly increased cerebrospinal fluid taurine levels. We suggest that such changes result from taurine release from astrocytes in brain into the extracellular fluid; this is consistent with taurine's role in the regulation of intracellular osmolarity in brain. Sequential measurements of amino acids in the cerebrospinal fluid of small rodents with indwelling cisterna magna catheters adds a useful new approach for exploring the neurobiology of hepatic encephalopathy in fulminant liver failure.

Samples of ventricular CSF were taken from 52 consecutive patients admitted for psychosurgery for intractable depression. Concentrations of asparagine, aspartate, glutamine, glutamic acid, and serine were determined. Glutamate and aspartate concentrations, implicated in excitotoxic brain damage, were not affected by various types of psychotropic drug treatment. Serine, a modulator of glutamate responses, was significantly elevated in samples from subjects receiving antidepressants. These subjects responded poorly to the operation. Psychotropic drugs are unlikely to be neurotoxic. Nevertheless, antidepressants may influence excitatory neurotransmission.

We evaluated the concentrations of the putative transmitter amino acids in the cerebrospinal fluid, and found a significant reduction of glutamate, aspartate, gamma-aminobutyric acid (GABA), and glycine concentrations in parkinsonian patients. There was no difference in amino acid concentrations between parkinsonian patients receiving L-DOPA and those not receiving L-DOPA. A similar decrease of glutamate and aspartate concentrations was found in patients with spinocerebellar degeneration. Concentrations of asparagine, glycine and taurine were also significantly decreased in patients with late cortical cerebellar atrophy.

The concentrations of GABA, glutamate, aspartate, glycine, taurine, glutamine, asparagine and alanine were determined in the CSF of 10 Senegalese baboons (Papio papio) following initial ketamine anaesthesia and subsequent administration (4 h later) of different compounds known to alter either inhibitory or excitatory neurotransmission. Ketamine itself was apparently without effect as the administration of a second dose of ketamine did not significantly alter the levels of any of the amino acids studied, although GABA levels tended to decrease. The presence of haemolysed material in occasional samples was associated with high GABA, glutamate, aspartate, taurine and asparagine levels. Therefore only haemolysate-free samples were included for analysis. Of the compounds administered, gamma-vinyl GABA had the most evident effect on CSF amino acid levels, increasing GABA (greater than 5-fold) and decreasing glutamate (greater than 50%), aspartate (40-50%), asparagine (20%) and alanine (30-35%) levels. The changes in GABA, glutamate and aspartate were still apparent 24 h post-gamma-vinyl GABA administration. In contrast, sodium valproate did not significantly alter the CSF levels of any of the amino acids studied. Upon acute administration allylglycine decreased the CSF concentrations of GABA and alanine, but not glutamate. These alterations are unlikely related to the occurrence of allylglycine-induced convulsions (in 2 of 4 experiments) as electroconvulsive shock did not alter CSF amino acid levels. During the experimental period encompassing the allylglycine injection (8 weeks), basal (initial post-ketamine, pre-drug sample) amino acid levels were abnormal with large increases in glutamate, GABA, aspartate and taurine whereas asparagine levels were below the limit of detection. Diazepam administration was followed by a significant increase in taurine and a decrease in aspartate levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebrospinal fluid (CSF) amino acid neurotransmitters, related compounds, and their precursors, choline levels, and acetylcholinesterase activity were measured in the CSF of patients with cerebellar ataxia during a randomized, double-blind, crossover, placebo-controlled clinical trial of physostigmine salicylate. The CSF gamma-aminobutyric acid, methionine, and choline levels, adjusted for age, were significantly lower in patients with cerebellar ataxia compared with controls. Physostigmine selectively reduced the level of CSF isoleucine and elevated the levels of phosphoethanolamine. No change occurred in CSF acetylcholinesterase activity and in the levels of plasma amino compounds in patients with cerebellar ataxia when compared with controls. Median ataxia scores did not statistically differ between placebo and physostigmine nor did functional improvement occur in any of the patients.

Concentrations of putative neuroactive substances glutamate, aspartate, gamma-aminobutyric acid, glycine, proline and ethanolamine were determined in ventricular cerebrospinal fluid collected in patients suffering from Parkinson's disease, pain syndromes or cerebellar tremor. Values are similar to those given in the literature for lumbar cerebrospinal fluid. A decrease in gamma-aminobutyric acid in Parkinson patients, as reported in lumbar cerebrospinal fluid, could not be observed. Further evidence for a rostro-caudal gradient for gamma-aminobutyric acid is supplied. New insights into pathophysiological mechanisms in any of the investigated syndromes may not be derived.

Amino acid concentrations were measured in CSF samples obtained by lumbar puncture in 51 patients, cervical puncture in 16 patients, spinal drains in nine patients, ventricular taps in five patients and from below a spinal block in six patients. There was evidence of a rostrocaudal gradient for GABA and taurine and a reverse gradient for alanine and asparagine. Lumbar CSF glycine concentrations rose with increasing age whilst GABA concentrations fell. Women had significantly lower concentrations of asparagine and glutamine and elevated taurine compared to men. The influence of biological factors and gradients must be taken into account before the interpretation of changes in CSF amino acid concentrations.

To classify the influence of neurotransmitters in the genesis of uremic encephalopathy we studied cerebrospinal fluid (CSF) and plasma (P) amino acid (AA) concentration, in patients undergoing various dialytic treatments (hemodialysis = HD, intermittent and continuous peritoneal dialysis = IPD and CAPD). HD causes a significant decrease in CSF/P ratios of branched chain AA (BCAA) and a significant increase in CSF Glycine/Valine ratio, suggesting an augmented brain uptake of Glycine at detriment of Valine. In IPD the general trend of Aromatic AA/BCAA ratio suggests a preferential transport of Aromatic AA through the blood brain barrier. The differences between IPD and HD are confirmed by data concerning metabolites of Serotonin and Dopamine: CSF concentrations of 5- Hydroxyindoleacetic acid and Homovanillic acid are low in HD but high in IPD. So, a reduced (in HD) and an increased (in IPD) activity of monoamine systems could be at the basis of some neurological disturbances appearing in uremia.

The reversed-phase liquid-chromatographic system described here is capable of resolving the neurotransmitter amino acids aspartic acid, glutamic acid, and gamma-aminobutyric acid (GABA) plus 21 other amino acids in cerebrospinal fluid (CSF) in a single analysis. The amino acids, derivatized with o-phthalaldehyde, are separated in 65 min. Concentrations of glutamine less than or equal to 600 mumol/L can be measured at the same time as GABA greater than or equal to 10 nmol/L. Using this method, we have determined reference intervals for amino acids, including GABA, in CSF in a group of pediatric patients who underwent lumbar puncture before myelography, and who were subsequently shown to have normal myelograms. These intervals are generally lower than those previously reported for childhood, but we believe this results from a more rigid selection of the control group. In addition, artifactual increases in concentrations of free neurotransmitters, caused by breakdown of amino acid conjugates, are minimized by (a) immediate freezing of the CSF samples to prevent enzyme-mediated changes, (b) omission of a deproteinization step, and (c) precolumn derivatization to reduce on-column breakdown of amide and peptide forms.

Concentrations of individual free amino acids were determined in lumbar cerebrospinal fluid (CSF) from patients with various complaints including histologically verified Alzheimer's dementia. Glycine and glutamine in the CSF of Alzheimer's dementia samples were lower than that of control samples. Only the concentration of glutamic acid in Alzheimer's dementia patients correlated with psychological measures. The reduction in glycine concentration was not specific for Alzheimer's dementia.

During a randomized, double-blind, crossover, placebo-controlled clinical trial of isoniazid (plus pyridoxine) in Huntington's disease (HD), amino acids and related amino compounds were measured in both cerebrospinal fluid (CSF) and plasma utilizing a newly developed high-performance liquid chromatography ion-exchange/fluorometric assay method. Results showed that isoniazid (plus pyridoxine) significantly elevated the mean (+/- S.E.M.) levels of gamma-aminobutyric acid, aspartate, asparagine, homocarnosine, ornithine, histidine, alpha-aminobutyric acid, isoleucine, leucine and alanine in CSF and the levels of beta-alanine in both CSF and plasma. These alterations can be traced to inhibition of decarboxylation and transamination reactions requiring the cofactor pyridoxal phosphate and may be related to the observed equivocal clinical response in the HD patients. The differential influence of isoniazid on plasma and CSF amino acid profiles suggests that alterations of CNS amino acid metabolism may be reflected in CSF, and that isoniazid-induced alterations of amino acid metabolism in the CNS differ from those in the periphery.

We evaluated changes of advanced liver disease and hepatic encephalopathy on the concentrations of amino acids (AA) and ammonia in plasma and cerebrospinal fluid (CSF) and of the neurotransmitters norepinephrine, dopamine and 5-hydroxytryptamine (5-HT) as well as the 5-hydroxyindole acetic acid (5-HIAA) in CSF before and at the end of a 3-day period of treatment with infusions enriched with branched chain amino acids (BCAA). The subjects studied were 13 patients with alcoholic cirrhosis and hepatic encephalopathy stages 1-3 (n = 8) and stage 4 (n = 5). The patients in coma stages 1-3 recovered during the treatment (survivors), those in coma stage 4 died before the study period was finished (non-survivors). The data emerging from this study show: Alterations of AA concentrations are much more pronounced in the CSF than in the plasma. In the case of tryptophan the alterations in plasma and CSF were inverse. Before the treatment the CSF-plasma ratios of the concentrations of BCAA and aromatic amino acids (AAA) are increased reflecting an activated transport of both the BCAA and AAA through the blood-brain barrier. High dose BCAA nearly normalized CSF concentrations and CSF-plasma ratios of AAA assuming that the treatment brought about an effective competition of cerebral uptake between BCAA and AAA. The CSF concentrations of ammonia and glutamine decreased significantly during treatment while the plasma concentrations changed only moderately. As to the neurotransmitters, only the concentrations of 5-HT and its metabolite 5-HIAA correlated with the clinical picture and with the concentration of their precursor AA.(ABSTRACT TRUNCATED AT 250 WORDS)