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Urinary 5-hydroxyindoleacetic acid and whole blood serotonin and tryptophan in autistic and normal subjects.

Urinary 5-hydroxyindoleacetic acid (5-HIAA) excretion in two consecutive collection periods (5:00 PM-11:00 PM and 11:00 PM-8:00 AM) and whole blood serotonin (5-HT) and tryptophan (TRP) were measured in groups of unmedicated autistics (n = 16), medicated autistics (n = 20), and normal controls (n = 27). Whole blood 5-HT values were significantly higher in unmedicated autistics compared to normal controls. No significant differences were found in 5-HIAA excretion (microgram/mg creatinine, mean +/- SD) between unmedicated autistics (4.07 +/- 1.52) and normal controls (3.50 +/- 1.07), or between medicated (5.35 +/- 2.93) and drug-free autistic individuals. No correlations were found between 5-HT values and urinary 5-HIAA excretion. Urinary 5-HIAA (microgram/mg creatinine, mean +/- SD) was significantly greater in hyperserotonemic autistic subjects (4.88 +/- 0.87) compared to normal controls (3.50 +/- 1.07, total collection period; p = 0.002). The relevance of these findings to the possibility that increased gut production of 5-HT might cause the elevated whole blood 5-HT levels seen in autism is discussed.

Adolescent↗

The effect of D-fenfluramine on brain 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in male and female rats.

Brain regional 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations were determined in freely feeding male and female rats 7 days after giving a single dose of D-fenfluramine (3.8 mg/kg, p.o.) or vehicle. Males showed negligible effects except for a significant decrease of 5-HT in the rest of the cortex, whereas females showed significant decreases of 5-HT and 5-HIAA in the frontal cortex, the rest of the cortex, hippocampus and hypothalamus; 5-HT was also decreased in female midbrain. Females had substantially higher plasma and brain concentrations of fenfluramine and moderately but significantly lower concentrations of norfenfluramine than the males. Plasma fenfluramine + norfenfluramine concentrations of the females were significantly higher than those of the males. Corresponding brain values showed smaller but significant differences. Female brain and plasma areas under the curve for fenfluramine + norfenfluramine (0-24 h after administration of D-fenfluramine) were 20 and 35% higher than male values. However, results suggest that the sex difference in the effect of D-fenfluramine on brain 5-HT metabolism is not due to differences in the metabolism of the drug.

Animals↗

Low cerebrospinal fluid 5-hydroxyindoleacetic acid concentration differentiates impulsive from nonimpulsive violent behavior.

Relationships of impulsive and nonimpulsive violent behavior to cerebrospinal fluid (CSF) monoamines and their metabolic concentrations were studied in thirty-six violent offenders. A relatively low 5-hydroxyindoleacetic acid (5HIAA) concentration was found in the CSF of impulsive violent offenders. This was not true for the offenders who had premeditated their acts. Other CSF monoamine or metabolite concentrations were not significantly different between the two groups. Of the groups studied, impulsive violent offenders who had attempted suicide had the lowest 5HIAA levels. A low CSF 5HIAA concentration may be a marker of impulsivity rather than violence.

3,4-Dihydroxyphenylacetic Acid↗

Effects of acute tryptophan depletion on plasma and cerebrospinal fluid tryptophan and 5-hydroxyindoleacetic acid in normal volunteers.

Brain serotonin synthesis and metabolism (turnover), as indicated by CSF concentrations of 5-hydroxyindoleacetic acid (5-HIAA), may depend on plasma concentrations of the essential amino acid L-tryptophan (TRP). We investigated the biochemical effects of acute plasma TRP depletion (ATD) in normal volunteers undergoing a 36-h CSF collection via lumbar drain. Six subjects who were in good health were put on a low-TRP diet (160 mg/day) 24 h before lumbar puncture; this diet was continued for the first 22 h of the CSF collection. At hour 22, subjects ingested a TRP-deficient 15-amino acid drink shown previously to deplete plasma TRP. Total plasma TRP, free plasma TRP, and CSF TRP subsequently decreased 86.3, 86.5, and 92.3%, respectively. CSF 5-HIAA decreased by 32.8%. Plasma total and free TRP concentrations were both decreased at approximately 2 h following ingestion of the TRP-free amino acid drink and were lowest approximately 6 h after ATD; CSF TRP and 5-HIAA were decreased at 2.5 h and approximately 4 h after ATD, respectively. CSF TRP was lowest 8.0 h later. CSF 5-HIAA continued to decrease 14 h after the TRP-deficient amino acid drink was given.

Adult↗

Simultaneous determination of 3-methoxy-4-hydroxyphenylglycol, 5-hydroxyindoleacetic acid, and homovanillic acid in cerebrospinal fluid with high-performance liquid chromatography using electrochemical detection.

An improved high-performance liquid chromatographic method with electrochemical detection (HPLC-EC) for the simultaneous determination of 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) in cerebrospinal fluid (CSF) of humans and nonhuman primates is described. Quantitation is based on the use of an internal standard, 5-fluoro-HVA. Sample preparation consists of mixing an aliquot of CSF with a solution of the internal standard followed by ultrafiltration. The precision of the method is high, with within-run and between-run coefficients of variation of 2-6% and less than 10%, respectively, in the concentration ranges of the metabolites encountered in human lumbar CSF. Accuracy was tested by comparing the present HPLC method with specific gas chromatographic-mass spectrometric (GS-MS) assays for MHPG and HVA and a GC-MS-validated HPLC assay for 5-HIAA: the correlations obtained were 0.968 for MHPG, 0.989 for 5-HIAA, and 0.999 for HVA, with no systematic bias between the methods. The use of ascorbate as a preserving agent for monoamine metabolites in CSF was not found to be necessary when proper care was exercised in sample handling and storage. The analysis of samples with up to 2% ascorbic acid was possible as well, but MHPG had to be assayed separately using an extraction procedure and an alternative internal standard, 3-ethoxy-4-hydroxyphenylglycol.

Animals↗

Venlafaxine but not bupropion decreases cerebrospinal fluid 5-hydroxyindoleacetic acid in unipolar depression.

BACKGROUND: While the antidepressants venlafaxine and bupropion are known to have different neurochemical profiles in vitro, their effects on human cerebral metabolism in vivo have not been directly compared. METHODS: Cerebrospinal fluid (CSF) levels of 5-hydroxyindoleacetic acid (5-HIAA), serotonin, 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid (HVA), and 3,4-dihydroxyphenylacetic acid (DOPAC) were examined in 14 never-hospitalized outpatients with unipolar depression and 10 age-similar healthy controls. Patients received a baseline lumbar puncture (LP), which was repeated after at least 6 weeks of randomized monotherapy with either venlafaxine or bupropion, while controls received only a baseline LP. RESULTS: Patients (n = 9) receiving venlafaxine showed a significant decrease (42%) in their CSF 5-HIAA concentrations after treatment, but no change in other CSF measures. In contrast, patients receiving bupropion (n = 8) showed no change in CSF measures compared to pretreatment values. CONCLUSIONS: While the mechanism for this differential effect of venlafaxine remains to be determined, the current study provides confirmation of the different aminergic effects of venlafaxine and bupropion.

Adult↗

A nonhuman primate model of type II excessive alcohol consumption? Part 1. Low cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations and diminished social competence correlate with excessive alcohol consumption.

Developmental, biochemical, and behavioral concomitants of excessive alcohol consumption were investigated using a nonhuman primate model. The variables of interest were: (1) interindividual stability of cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) from infancy to adulthood, (2) effect of parental deprivation early in life on adult CSF 5-HIAA concentrations; (3) correlations between CSF 5-HIAA and 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations and alcohol consumption; and (4) correlation between the frequency of competent social behaviors and alcohol consumption. Twenty-nine rhesus macaques were reared for their first 6 months either with their mothers or without adults in peer-only conditions. At 6 and 50 months of age, each subject underwent a series of four, 4-day social separations. Cisternal CSF was sampled before and during the first and last separations; concomitantly, observational data were collected on social dominance behavior in the home-cage. When they reached 50 months of age, the monkeys were provided free access to a palatable alcohol solution daily for 1-hr periods before, during, and after the social separations. Before and after the 50-month separations, data were collected on all types of social behavior in the home-cage. Results showed that peer-reared subjects consumed more alcohol than mother-reared subjects during baseline conditions. Mother-reared subjects, however, increased their rates of consumption to equal peer-reared subjects' rates of consumption during the conditions of a social separation stressor. Peer-reared subjects also exhibited lower CSF 5-HIAA concentrations in infancy and adulthood than their mother-reared counterparts. With rearing condition held constant, interindividual differences in CSF 5-HIAA, MHPG, and homovanillic acid were stable from infancy to adulthood, and high rates of alcohol were consumed by the young adult monkeys with low CSF 5-HIAA and MHPG concentrations, particularly when the CSF was obtained during the social separations. High rates of alcohol consumption were also observed in subjects with infrequent social interactions and less competent social behaviors. In contrast to the human data, we found no gender differences in rates of alcohol consumption, nor in the correlations between alcohol consumption and the other variables. With some exceptions, findings from the study are generally consistent with predictions from Cloninger's type II model of excessive alcohol consumption in men with low CSF 5-HIAA, who also exhibit impaired impulse control and violent and antisocial behaviors.

Adult↗

[Effect of the genotype on the serotonin and 5-hydroxyindoleacetic acid content in different sections of the mouse brain].

The levels of serotonin and 5-hydroxyindoleacetic acid contents were estimated in hypothalamus, hyppocampus and midbrain of inbred mice of 12 strains. The levels of serotonin and its metabolite in various parts of brain representing different links of its serotoninergic system were shown to be genetically determined. The correlation analysis revealed that there were two, relatively autonomous genetic systems controlling biosynthesis and catabolism of serotonin in brain.

Animals↗

Serotonin and 5-hydroxyindoleacetic acid concentrations in individual hypothalamic nuclei and other brain areas of rat.

Serotonin and 5-hydroxyindoleacetic acid (5-HIAA) were measured in individual nuclei of rat hypothalamus and other brain areas using HPLC with electrochemical detection. 5-HIAA levels were first demonstrated in hypothalamic and some discrete brain areas. The 5-HIAA/5-HT ratio was highest in the n. caudatus putamen, high in the n. ventromedialis and lowest in the n. suprachiasmaticus.

Animals↗

Regional concentrations of serotonin, tryptophan, 5-hydroxyindoleacetic acid, dopamine, and norepinephrine in the ovine brain.

Regional concentrations of tryptophan, serotonin (5HT), 5-hydroxyindoleacetic acid (5HIAA), norepinephrine, and dopamine were determined in the ovine brain. Tryptophan concentrations varied between 18.6 nmoles/g of tissue (hypothalamus, midbrain) and 26.9 nmoles/g (cerebellum). The 5HT concentrations varied 0.34 nmoles/g (cerebellum) and 3.75 nmoles/g (midbrain). The concentration of 5HIAA varied between 1.78 nmoles/g (cerebellum) and 5.02 nmoles/g (hypothalamus). Large concentrations of norepinephrine were found in the hypothalamus (4.37 nmoles/g) and midbrain (2.08 nmoles/g), while the frontal cortex, thalamaus, hippocampus, and cerebellum were all relatively low in norepinephrine (0.65 to 0.95 nmoles/g). The concentration of dopamine was between 0.32 nmoles/g (hippocampus) and 39.8 nmoles/g (caudate nucleus). Generally, the distribution of these compounds in the ovine brain is similar to their regional distribution in other mammalian species. It was observed, however, that the ratio of 5HT/5HIAA appears to be relatively lower in sheep than in other species, suggesting that interspecies differences in the metabolism of 5HT or elimination of 5HIAA (or both) may exist.

Animals↗

Aging and diurnal rhythms of pineal serotonin, 5-hydroxyindoleacetic acid, norepinephrine, dopamine and serum melatonin in the male rat.

Pineal serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), norepinephrine (NE) and dopamine (DA) were measured by high-pressure liquid chromatography with electrochemical detection and serum melatonin was measured by radioimmunoassay in rats aged 3 weeks, 8 weeks and 18 months. They were killed either at mid-light or mid-dark of a 12 h light:12 h dark cycle. Diurnal rhythms were observed for 5-HT and 5-HIAA in all ages studied while those for NE and DA were not observed in the 18-month-old animals. Pineal 5-HT and 5-HIAA were higher in 3-week-old rats at mid-dark, and lower at mid-light than in older animals. The pineal content of NE was lower in the 3-week-old rats at mid-dark and mid-light compared with that in the 8-week-old while the DA content was lower at mid-dark. In addition, pineal 5-HT, 5-HIAA, NE and DA were lower in the 18-month-old than in the 8-week-old animals at mid-dark. At mid-dark serum melatonin levels showed an age-related decrease. This study shows that an age-related decrease of pineal 5-HT, 5-HIAA, NE and DA can only be demonstrated at mid-dark and that the age-related decrease of melatonin may not be due to a decrease in sympathetic activity.

Aging↗

Dark-rearing modifies serotonin and 5-hydroxyindoleacetic acid contents in specific regions of rabbit brain.

The contents of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in specific brain regions of rabbits dark-reared from birth until 3 months of age are higher than those of controls. After light exposure, 5-HT and 5-HIAA levels become similar to normal values. In adult rabbits kept in darkness for 3 months, 5-HT and 5-HIAA contents increase only in the superior colliculi. These results are discussed in relation to the early development of the vestibulo-ocular reflex.

Afferent Pathways↗

Developmental changes of serotonin and 5-hydroxyindoleacetic acid levels in specific regions of the pigeon central nervous system.

Serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels were determined in the visual Wulst, optic lobes, retina, cerebellum and brainstem of the pigeon during embryonic and posthatching periods. 5-HT content increased during development in almost all regions. 5-HIAA content generally showed the highest values within the second posthatching week and then decreased to reach adult values. The high 5-HT turnover (as indicated by high (5-HIAA/5-HT ratio) observed over the first posthatching week suggests a possible role of 5-HT on developmental processes which occur in pigeon visual areas over the same time.

Aging↗

Spot urine 5-hydroxyindoleacetic acid levels in the early diagnosis of acute appendicitis.

BACKGROUND/PURPOSE: The significance of spot urine 5-hydroxyindoleacetic acid (5-HIAA) levels in the early diagnosis of acute appendicitis (AA) is questioned. METHODS: Forty young, pigmented, male rabbits were divided into 4 groups. Groups are summarized as follows: group 1, control (n = 10); group 2, laparotomy, sham (n = 10); group 3, peritonitis with cecal ligation and puncture (n = 10); and group 4, experimental appendicitis (n = 10). Spot urine samples were obtained for 5-HIAA determination, and appendectomy materials were examined histopathologically and peritoneal fluid cultures were obtained after 12 hours in the study groups. The results were analyzed statistically with 1-way analysis of variance and Scheffé and Tukey's HSD tests. RESULTS: The mean 5-HIAA levels in the control group was 5.7 +/- 0.6 mg/L, whereas it is 5.9 +/- 0.9 mg/L, 6.6 +/- 0.6 mg/L, 9.4 +/- 0.9 mg/L in the sham, peritonitis, and appendicitis groups, respectively. The levels of 5-HIAA in the appendicitis group were higher than those in the other groups, which was statistically significant (P < .001). CONCLUSIONS: Spot urine 5-HIAA determination may be a practical, objective, and noninvasive method in the early diagnosis of AA. Because other radiological and laboratory tests can be insufficient, especially in the early period of AA, this test may be used effectively instead. Clinical studies are necessary for further conclusions.

Acute Disease↗

Comparative simultaneous measurement of cerebrospinal fluid 5-hydroxyindoleacetic acid and blood serotonin levels in delirium tremens and clozapine-induced delirious reaction.

Cerebrospinal fluid 5-hydroxyindoleacetic acid and total blood serotonin levels were measured simultaneously in 11 female patients with delirium tremens and nine schizophrenic women with clozapine-induced acute delirium. Both groups had significantly raised levels of 5HIAA in CSF and significantly reduced blood 5HT levels as compared with normal control subjects, symptom-free alcoholics, or clozapine-treated schizophrenics. The two delirious groups were not distinguishable from each other in respect of their CSF 5HIAA or blood 5HT values. After clinical recovery both values returned to normal levels.

Adult↗

Urinary excretion of 5-hydroxyindoleacetic acid and N1-methyl-2-pyridone-5-carboxamide by normal and phenylketonuric children.

Excretion of 5-hydroxyindoleacetic acid (5-HIAA) and N1-methyl-2-pyridone-5-carboxamide (N1MPC) was determined before and after an oral load of tryptophan in 9 phenylketonurics on free diet and with severe mental retardation and in 8 normal subject without any drugs. Before loading, excretion of these end metabolites of the serotonin and the kynurenine pathways, respectively, of tryptophan metabolism was only slightly lower in the phenylketonurics. But after loading, excretion of 5-HIAA increased more in the patients than in the controls, the reverse being true for N1MPC. These findings are interpreted as suggesting that function of the kynurenine pathway may be more disturbed in PKU than that of the serotonin one.

Child↗

Biological correlations of suicide and aggressivity in major depressions (with melancholia): 5-hydroxyindoleacetic acid and cortisol in cerebral spinal fluid, dexamethasone suppression test and therapeutic response to 5-hydroxytryptophan.

5-Hydroxyindoleacetic acid (5-HIAA) and cortisol in cerebrospinal fluid (CSF), response of the dexamethasone suppression test (DST) and the clinical response to treatment with 5-hydroxytryptophan (5-HTp) plus carbidopa were studied in a group of 21 depressed inpatients (major depression with melancholia) in order to correlate biological findings with psychopathologicalones. A positive correlation was found between strong suicidal thoughts, suicidal attempts and self-aggressivity and low concentration of 5-HIAA in CSF and a less significant but still positive correlation with abnormal DST response and with clinical response to the treatment.

5-Hydroxytryptophan↗