Plasma levels of MHPG, HVA and total 5-HIAA in depression. Preliminary study]

This study was aimed at assessing monoamine catabolites plasma levels in depressed patients and healthy volunteers. Plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) of 21 control subjects and 26 depressed patients (according to DSM III-R criteria) were measured at baseline (day 0) and day 4, day 7, day 30 of prescribed antidepressant treatment. The clinical assessment, at baseline as well as during treatment, used the Hamilton depression rating scale and the BPRS. Our data show the interest of these results in predicting response. The respondent patients showed a significant decrease in plasma MHPG level at J7, contrary to non-respondent patients. Moreover, a positive correlation between plasma levels of MHPG and HVA before any prescribed antidepressants was found only with respondent patients. The lack of correlation for non-respondent patients can suggest that the relationships between this monoamine systems should be disrupted in these patients. Significant relationships appear between clinical symptoms and plasma catabolites, allowing us to consider new physiopathological aspects of the depressive picture. The 3 monoamines seemed involved in sleep disorders. Perturbations of norepinephrine and serotonin metabolism could intervene in suicidal ideation and behaviour. Motor activity was associated with a modification in dopamine and serotonin metabolism. Moreover significant correlations were observed between items referring to thought content and monoamine plasma catabolites such as MHPG and blunted affect, 5-HIAA and obsessions, HVA and guilt feelings, devalorization and without hope items.(ABSTRACT TRUNCATED AT 250 WORDS)     

CSF 5-HIAA and HVA concentrations in elderly depressed patients who attempted suicide.

CSF findings distinguished 12 elderly depressed patients who attempted suicide from nine depressed patients who did not and from seven normal control subjects. Psychosocial factors and measures of psychopathology did not differentiate suicidal from nonsuicidal patients. Biochemical factors may be important in evaluating suicide risk in the elderly.     

Concentration gradients for HVA, 5-HIAA, ascorbic acid, and uric acid in cerebrospinal fluid.

Concentrations of HVA, 5-HIAA, ascorbic acid, and uric acid in the lumbar and cisternal cerebrospinal fluid (CSF) were measured in psychiatric and neurologically impaired patients. The concentration of HVA is 6.1 times and of 5-HIAA 2.7 times higher in cisternal than in lumbar samples, the cisternal level of uric acid is half that of the lumbar region, but no significant differences were found in ascorbic acid concentrations. Correlation between lumbar and cisternal metabolite concentrations is high for 5-HIAA and ascorbic acid, and is less for HVA and uric acid. In cisternal CSF there is a significant correlation between levels of HVA-5-HIAA, 5-HIAA-ascorbic acid, and 5-HIAA-uric acid. These correlations disappear in lumbar CSF. These findings indicate that extrapolations to cisternal neurotransmitter metabolite concentration from lumbar measures are unwarranted for HVA, but not for 5-HIAA.     

Relationship between platelet MAO activity and concentrations of 5-HIAA and HVA in cerebrospinal fluid in chronic pain patients

Summary Platelet monoamine oxidase (MAO) activity and concentrations of 5-HIAA and HVA in the cerebrospinal fluid (CSF) were estimated in a series of 54 chronic pain patients. Platelet MAO activity was found to correlate, positively to CSF concentrations of 5-HIAA and HVA, which had been adjusted in order to eliminate the influence of age and body height. However, only the correlation with 5-HIAA reached a significant level. When partial correlations were sought, only the positive correlation between platelet MAO activity and CSF 5-HIAA remained. The results support the notion that platelet MAO ia a biological marker for some trait dependent property of the central serotonergic system.Supported in part by grants from the Swedish Medical Research Council (grants No. 166, 4145 and 5740).     

The concentrations of GABA, 5-HIAA and HVA in the cerebrospinal fluid of children with infantile spasms and the effects of ACTH treatment.

Children with infantile spasms (IS) are generally treated with ACTH although little is known of the biochemical basis of the symptoms and the mechanism of this therapy. We have measured the concentrations of gamma-aminobutyric acid (GABA), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in the CSF of IS children, followed the effect of ACTH treatment on these parameters and correlated CSF GABA values with the cause of IS, cranial CT findings and antiepileptic treatment. While significant differences in GABA concentrations were found between the children with IS and those with febrile seizures or nonconvulsive symptoms, these could be accounted for by age, not the disease present. The CSF GABA level was highest in the IS children with normal CT, cryptogenic cause and no antiepileptic treatment, and lowest in those with abnormal CT, symptomatic cause and antiepileptic treatment. The basal level of CSF 5-HIAA in the IS children was higher than that in the nonconvulsive children, but HVA levels did not differ. ACTH therapy did not change the CSF levels of GABA, 5-HIAA and HVA significantly.     

Simultaneous determination of DOPAC, MHPG, 5-HIAA and HVA in CSF by direct injection on a liquid chromatograph with coulometric detection.

We describe a direct analysis for simultaneous determination of 3,4-dihydroxyphenylacetic acid (DOPAC), 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and 4-hydroxy-3-methoxyphenylacetic acid (HVA). After ultrafiltration the samples are applied directly to a high-performance liquid chromatograph with coulometric detection. The appropriate choice of the potentials of the three-coulometric-electrode system eliminates many possible interfering substances. One chromatographic run requires less than 15 min. By this analytical system the lowest amount of DOPAC, MHPG, 5-HIAA and HVA detectable was 0.16, 0.18, 0.90, and 1.48 ng/ml respectively. Coefficient of variation was less than 5% for "within-run" precision and less than 10% for "between-run" precision.     

Brain cortex phospholipids liposomes effects on CSF HVA, 5-HIAA and on prolactin and somatotropin secretion in man

Summary Liposomes obtained from bovine brain cortex phospholipids (BC-PL), which display several effects on brain function in mice, have been administered intravenously (200 mg) to healthy subjects at various times before diagnostic lumbar puncture. HVA and 5-HIAA concentrations in CSF have been evaluated with the aim of assessing changes of monoamines metabolism. An increase of HVA occurs after 2 hours from BC-PL administration, reaching its peak after 6–7 hours. The finding is interpreted as an index of an increased turnover of brain DA. 5-HIAA changes are less impressive and a smaller increase of the metabolite is observed. They cannot correctly be related to brain changes of serotonin metabolism, since 5-HIAA originates also from the spinal cord. No effects are observed on the secretion of prolactin, but somatotropin increases sharply between 2 and 7 hours from treatment, suggesting the possibility of an activation of the dopaminergic pathway, stimulating STH secretion.     

Intranasal vasotocin decreases cerebrospinal fluid 5-HIAA levels in man

A single dose (10 ng/kg) of the nonapeptide arginine vasotocin (AVT) administered intranasally to healthy young men, significantly decreased 5-HIAA levels in the lumbar cerebrospinal fluid (CSF) 8 hr after its administration. So far, this represents the smallest amount of an active substance able to alter CSF 5-HIAA levels in man. It is suggested that the decrease of CSF 5-HIAA levels after AVT administration reflects an AVT-induced reduction of the brain 5-HT turnover.     

Lateral ventricle-brain ratio and balance between CSF HVA and 5-HIAA in schizophrenia.

OBJECTIVE: Lateral ventricle enlargement in schizophrenia has been positively correlated with poor premorbid competence, negative symptoms, and poor treatment response and negatively correlated with concentrations of homovanillic acid (HVA), a dopaminergic metabolite. The authors provide further evidence of a reciprocal relationship between lateral ventricle size and dopaminergic activity in schizophrenia. METHOD: They assessed the relationship between lateral ventricle enlargement (ventricle-brain ratio, VBR) and CSF neurotransmitter metabolite concentrations (HVA and 5-hydroxyindoleacetic acid [5-HIAA]) in 45 patients with schizophrenia, 28 with affective disorders (19 patients with major depression and nine with bipolar disorder), and 91 normal comparison subjects. RESULTS: No group mean differences were significant. Although individual correlations of VBR with HVA and 5-HIAA were not statistically significant, the ratio of HVA to 5-HIAA was significantly correlated with VBR in the patients with schizophrenia, a finding consistent with dopaminergic-serotonergic balance hypotheses. CONCLUSIONS: These data suggest that it is the balance between HVA and 5-HIAA rather than their absolute levels which is associated with brain morphology and that this relationship between brain chemistry and morphology may be characteristic of the normal range of functioning for these systems. In other words, independent of whether brain morphology and chemistry differentiate psychopathological from nonpsychopathological states, there may be an orderly relationship between lateral ventricle size and the balance between HVA and 5-HIAA balance that is especially prominent in schizophrenia.     

The daily rhythm of HVA,VMA, (VA) and 5-HIAA in depressionsyndrom

Summary The daily rhythm (8–14 h, 14–20 h, 20–2 h, 2–8 h) of HVA, VMA, (VA) and 5-HIAA was studied in 21 depressed patients and was compared to the values of 13 healthy subjects. In healthy subjects all compounds trend to high values during day-time and significant lower values in the nightphase (2–8 h). Depressed patients did not show a significant rhythm during the four fractions; the values of HVA and VMA were significant lowered in the morning-phase (8–14 h). This demonstrates a good connexion to the clinical feature with the morning listlessness. Normal concentrations were reached in the night-phase (2–8 h). 5-HIAA did not show any significance between healthy subjects and depressed patients during the circadian rhythm. The ratio VMA/HVA in healthy subjects fell significant from morning-phase (8–14 h) to night-phase (20–2 h, 22–8 h). In depressed patients the ratio was approximately equal in all fractions. Whereas the ratio 5-HIAA×100/ VMA>+HVA increased from the morning-phase to the night-phase in healthy persons, this ratio did not show any significance in the four fractions of depressed patients.Also these results suggest some importance in explaining the lost of drive in the activity of depressed patients during morning hours and the remission of these patients often observed in the evening. A very good correlation to the clinical feature is emphasized.Preliminary studies on 6 patients with different depressive diagnosis during depression- and remission-phase gave a different biochemical pattern. Further extended studies have to be carried out to differentiate exactly between nosological different depressions.     

Isoniazid effects on choreiform movement and on GABA, HVA and 5-HIAA in CSF

Isoniazid was administered in 4-week open trial in patients with choreiform movement. Gamma-aminobutyric acid (GABA), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in CSF were measured before and after treatment. Isoniazid did not improve choreiform movement. CSF GABA levels were significantly increased after treatment, but HVA and 5-HIAA levels were not significantly altered. The findings suggest that isoniazid influenced brain GABA metabolism but did not influence dopamine and serotonin metabolism in patients with chorieform movement.     

Changes in urinary levels of MHPG, VMA and 5-HIAA and plasma tryptophan in post-partum blues. Initial results

In post-partum depressive illness ("post-partum blue") we measured urinary MHPG, VMA, 5-HIAA and free and total Trp. VMA and especially MHPG reflect the brain noradrenaline metabolism. Trp is the precursor of 5-HT synthesis and 5-HIAA is the main urinary catabolite of 5-HT. The clinical evaluation consisted in self-evaluation scales: Pitt scale 1, 3 and 5 days after delivery, CESD scale of NIMH (depression) and BONIS scale (anxiety) at 6th day. Moreover a psychiatrist measured depression intensity on the MADRS scale and DSM III data. First results seem to indicate a decrease of free MHPG and VMA, an increase of 5-HIAA and no alteration of free and total Trp. These modifications could involve adrenergic and serotoninergic alterations in brain.     

The relationship between CSF HVA/5-HIAA ratio and suicide intent in suicide attempters.

There is a need to find stable biomarkers for suicidal behavior and suicide prediction. Reduced homovanillic acid/5-hydroxyindolacetic acid (HVA/5-HIAA) ratios in cerebrospinal fluid (CSF) in depressed suicide attempters have been reported. Suicide intent is a predictor of repetition of attempts and suicide. In the present study we investigated the relationship of HVA/5-HIAA ratio to the scales rating suicide intent and depressive symptoms. Fifteen consecutive medication-free male suicide attempters admitted to a psychiatric ward at the Karolinska Hospital and eight healthy male volunteers underwent lumbar puncture and had the CSF monoamine metabolite levels assayed. Patients were assessed with the Beck Suicide Intent Scale (SIS), the Montgomery Asberg Depression rating Scale (MADRS) and the Chapman Scale of Anhedonia. Within the suicide attempter group, HVA/5-HIAA ratio was significantly associated with the Suicide Intent Scale (SIS), but not with the MADRS scale or the Chapman Scale of Anhedonia indicating that the HVA/5-HIAA ratio may be a biomarker of suicide intent.     

阴性精神分裂症认知功能改善与HVA和5-HIAA的关系

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

Serotonergic measures in suicide brain: the concentration of 5-HIAA, HVA, and tryptophan in frontal cortex of suicide victims.

Concentrations of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and tryptophan (TRP) were determined in the frontal cortex of individuals who died by suicide, homicide, accident, or the result of physical diseases. Females had significantly higher tryptophan concentrations than males. There was a significant correlation HVA and the interval between death to refrigeration of the body. Mean HVA levels were higher from noon to 5 PM. Suicide and homicide victims had significantly higher cortical HVA concentrations than those who died of physical disease but not accident victims. This was not accounted for by gender, age, postmortem interval from death to refrigeration of the body or to autopsy, specimen storage time, or drug effects. The ratio of HVA/5-HIAA was also significantly higher in suicides compared with those who died of physical disease. No differences in cortical 5-HIAA or tryptophan concentrations between the four groups were found. There were no differences in the levels of the three substances in violent and nonviolent suicides. There were no significant correlations between 5-HIAA, HVA and TRP concentrations in all subjects or any of the four subgroups. The implications of these findings for the role of serotonin and dopamine in suicide and violence are discussed.     

Tapping-time influences concentrations of 5-HIAA in the CSF

Lumbar puncture was performed on 12 healthy male volunteers at the L 4–5 level to investigate the influence of tapping-time on CSF levels of transmitter metabolites.

Applying a backward multiple regression model to the data, height, age and tapping-time was found to influence 5-HIAA while HVA correlated only with height. Also HMPG was influenced by height, but the distance from the external occipital protuberance to the site of puncture made a contribution.

The present results indicate that tapping-time might be a factor of importance when using CSF concentrations of 5-HIAA as a measure of serotonin turnover.