3-methoxy-4-hydroxyphenylglycol-sulfate and Depressive-Disorder

The possible relationship between a number of biochemical parameters and measures of pain and depression was studied in chronic pain patients without a major depression. In a double-blind crossover study, patients were treated with amitriptyline combined with a low dose of flupentixol or placebo. We investigated whether pretreatment biochemical values correlated with initial data on pain and/or depression, or whether they had predictive value for treatment outcome. We also studied systematically the effect of both treatment regimes on the biochemical parameters themselves and their relation to the plasma levels of amitriptyline. From our results, the possible involvement of the serotonin system in somatoform pain disorder is confirmed and no direct relation with the noradrenergic system could be inferred. The lack of involvement of a number of putative, depression-related, biochemical parameters suggests that affective disorders and pain syndromes do not share all mechanisms in common.

Topics: Adult; Amitriptyline; Depressive Disorder; Double-Blind Method; Drug Therapy, Combination; Female; Flupenthixol; Humans; Male; Methoxyhydroxyphenylglycol; Middle Aged; Pain; Pain Measurement; Personality Inventory; Serotonin; Somatoform Disorders

Cimoxatone is a new monoamine oxidase inhibitor (MAOI) in comparison to the existing non-selective and irreversible MAOIs used in the therapy of depression. A clinical study has been carried out in 10 depressed patients. Cimoxatone was given from 0.32 to 0.78 mg/kg/day for 28 days. The drug was shown to be effective against depression and well tolerated at the given doses. The inhibition of monoamine oxidase and its reversibility were assessed by urinary excretion of 3-methoxy-4-hydroxy- phenylethyleneglycol sulphate. The treatment had no effect on the plasma prolactin levels. The plasma concentrations of cimoxatone reached a plateau after 3 to 4 days of therapy. The study confirmed earlier findings in healthy volunteers that the principal metabolite is also active as a type A MAOI. The plasma elimination of cimoxatone and its metabolite is almost complete 4 days after the last dosing.

Topics: Adult; Clinical Trials as Topic; Depressive Disorder; Female; Humans; Kinetics; Male; Methoxyhydroxyphenylglycol; Middle Aged; Monoamine Oxidase Inhibitors; Oxazoles; Oxazolidinones; Prolactin

The serotonin (5-hydroxytryptamine) transporter (5-HTT) is considered to affect the pathogenesis of mood disorders. Large number of genetic association studies between 5-HTT functional polymorphisms and vulnerability of mood disorders and therapeutic response to antidepressants has been carried out. We investigated the influence of 5-HTT-linked polymorphic region (5-HTTLPR) and 5-HTT 17 bp variable number of tandem repeat polymorphism (5-HTTVNTR) polymorphisms on concentrations of monoamine metabolites in cerebrospinal fluid (CSF) among treatment-resistant patients with mood disorders. Subjects were 119 Swedish patients with persistent mood disorders and 141 healthy subjects. In 112 of these patients, we measured 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol in CSF. Genotyping for 5-HTT polymorphisms from genomic DNA was carried out by PCR. There was no significant difference in allele/genotype frequency between patients and healthy subjects. In patients with mood disorders, we found significant difference in mean 5-HIAA concentration between 5-HTTLPR genotypes (p=0.03). Although the 5-HIAA concentration showed a tendency to be higher in short (S) carriers than in non-S carriers of the 5-HTTLPR in patients (p=0.06), when considering patients with major depressive disorder (MDD), the 5-HIAA concentration was significantly higher among S carriers than among non-S carriers (p=0.02). Moreover, the 5-HIAA concentration was higher in S/S subjects compared to long (L)/L (p=0.0001) and L/S (p=0.002) subjects in patients with MDD. Similarly, there was higher HVA concentration in S/S subjects compared to L/L (p=0.002) and L/S subjects (p=0.002). There was no effect of 5-HTTVNTR. Our findings show that the 5-HTTLPR polymorphism affects 5-HIAA and HVA concentrations among treatment-resistant patients with mood disorders.

Topics: Adult; Aged; Biogenic Monoamines; Brain Chemistry; Depressive Disorder; DNA Mutational Analysis; Drug Resistance; Female; Genetic Predisposition to Disease; Genetic Testing; Genotype; Homovanillic Acid; Humans; Hydroxyindoleacetic Acid; Male; Methoxyhydroxyphenylglycol; Middle Aged; Mutation; Polymorphism, Genetic; Serotonin Plasma Membrane Transport Proteins; Tandem Repeat Sequences; Up-Regulation

The plasma levels of free and sulfoconjugated forms of 3-methoxy-4-hydroxyphenylglycol (MHPG) were examined before and after treatment in 16 patients with unipolar major depressive disorders without melancholia. The patients were treated with intravenous administration of clomipramine for 4 weeks. Seven depressive disorder patients who showed marked improvement (the improvement group) revealed significant reduction in their plasma sulfoconjugated MHPG levels. In 6 depressive disorder patients who showed no improvement (the no-improvement group), the plasma sulfoconjugated MHPG levels showed no significant change after treatment. The remaining 3 patients, who showed ambiguous change after treatment, were excluded from the analysis. Levels of plasma-free MHPG showed significant change after treatment in neither the improvement group nor in the no-improvement group. It is suggested that levels of plasma sulfoconjugated MHPG may serve as an indicator of brain noradrenergic activity.

Topics: Adolescent; Adult; Aged; Clomipramine; Depressive Disorder; Dose-Response Relationship, Drug; Female; Humans; Infusions, Intravenous; Male; Methoxyhydroxyphenylglycol; Middle Aged; Norepinephrine; Personality Inventory; Treatment Outcome

The plasma NE concentration was assayed with HPLC-ED and 24 hour urinary MHPG-SO4 excretion was determined in 23 endogenous depressed patients and 17 normal controls. In normal controls, plasma NE concentration was significantly correlated with age and was significantly higher in female than that in male. Plasma NE level in endogenous depressed patients was statistically higher than that in the age- and sex-matched controls (paired t test, P less than 0.05). The causes of the result difference among the past plasma NE studies was discussed and the necessity to design the age- and sex-matched controls in the future plasma NE study was suggested.

Topics: Depressive Disorder; Female; Humans; Male; Matched-Pair Analysis; Methoxyhydroxyphenylglycol; Norepinephrine

Much evidence indicates that urinary 4-hydroxy-3-methoxyphenylethyleneglycol (MHPG) is an insensitive measure of central norepinephrine metabolism. This conclusion, however, seems to apply mainly to total urinary MHPG, since previous findings point to the possibility that the major proportion of urinary MHPG sulfate originates in the CNS, while most urinary MHPG glucuronide originates in peripheral organs. To examine this hypothesis, experiments were performed by which we altered MHPG turnover in man at two different stages: firstly, strong physical exercise (ergometer) increased the urinary excretion rate of MHPG glucuronide and not that of MHPG-sulfate; secondly, ethanol (l g/kg), which is known to block the metabolism of MHPG to vanilmandelic acid in the liver, increases the urinary excretion rate of the glucuronide and not that of sulfate. Both experiments indicate that alteration of peripheral norepinephrine turnover changes the urinary excretion of MHPG glucuronide only and not that of sulfate, thus providing strong, albeit indirect, evidence for a primarily central origin of MHPG sulfate. Preliminary experiments in 32 depressed patients showed little difference in both MHPG fractions compared with healthy controls, apart from a slightly reduced excretion rate of glucuronide. These findings fail to provide any evidence of central, and only small changes in peripheral norepinephrine metabolism in depression.

Topics: Adult; Brain; Depressive Disorder; Female; Glycols; Humans; Male; Methoxyhydroxyphenylglycol; Middle Aged; Norepinephrine; Receptors, Adrenergic; Sex Factors

Topics: Alprazolam; Biomarkers; Depressive Disorder; Glycols; Humans; Methoxyhydroxyphenylglycol; Norepinephrine

Topics: Adult; Alprazolam; Biomarkers; Depressive Disorder; Female; Glycols; Humans; Male; Methoxyhydroxyphenylglycol; Middle Aged; Psychiatric Status Rating Scales

The Dexamethasone Suppression Test (DST) was performed in 64 depressed inpatients, in 48 schizophrenics, and in 20 normal controls. Thirty-four percent of depressive inpatients were found to escape from dexamethasone suppression significantly higher than either schizophrenics (13%) or normal subjects (5%). Among subgroups, bipolar and unipolar endogenous depression patients had much higher abnormal rates for the DST (59% and 48%, respectively) than nonendogenous cases (8%). DST results were also found to be positively correlated with patients' Hamilton scores. These findings suggested that DST could be helpful in diagnosis, discrimination of subtypes, and in assessment of severity of symptoms. In 32 of the 64 depressed inpatients, urinary MHPG X SO4 excretion was determined and compared with 21 normal controls. Bipolar patients (n = 7) had less MHPG X SO4 excretion than unipolar endogenous patients (n = 16). Excretion was positively correlated with cortisol level at 17 hr after dexamethasone administration in 32 depressive inpatients, especially in the unipolar subgroup. A trend toward negative correlation, though not statistically significant, was found in bipolar depression between cortisol levels at 17 hr after dexamethasone administration and urinary MHPG X SO4 excretion. This may indicate that some differences in norepinephrine (NE) metabolism may exist between unipolar and bipolar depression, leading to differing correlations between deviation of central NE function and hypothalamus-pituitary-adrenal (HPA) axis in different subgroups of depression.

Topics: Adult; Bipolar Disorder; Depressive Disorder; Dexamethasone; Female; Glycols; Humans; Hydrocortisone; Male; Methoxyhydroxyphenylglycol; Schizophrenia

Topics: Adult; Blood Platelets; Depressive Disorder; Female; Glycols; Humans; Hydrocortisone; Male; Methoxyhydroxyphenylglycol; Middle Aged; Monoamine Oxidase

A number of arguments support the hypothesis that changes in urinary levels of MHPG sulfate and MHPG glucuronide respectively reflect central and peripheral norepinephrine metabolism (NE) in man. In this line, the daily excretion of both conjugates was determined in 36 depressed women comparatively to 23 healthy women in order to assess the extent and the central or peripheral location of their possible NE dysfunction. About 80% of the patients suffering from depression (6 endogenous, 19 neurotic, 11 reactive depressions) exhibited a central NE defect, as evidenced by low MHPG sulfate, and many of them had probably also diminished sympathetic activity, as suggested by low MHPG glucuronide. Clinical symptoms possibly related to the psychic state (mood alteration) or associated to sympathetic changes (anxiety, motor activity) respectively altered sulfate or glucuronide excretion. Sulfate (S) and glucuronide (G) MHPG excretions were significantly correlated in healthy subjects (r = 0.53, p = 0.01), thus supporting the concept of the functional link between central NE activity and sympathetic function. Such a correlation was not found in depressive patients. However the lack of significant changes in the mean ratio S/G in the patient sub-groups suggests that as in normal subjects, central and peripheral NE activity are linked in depressed patients, but other factors may also modify sympathetic function. Taken together our data show that the separate assay of sulfate and glucuronide MHPG provides a better picture of NE dysfunction in depression than total MHPG measurement.

Topics: Adjustment Disorders; Adult; Aged; Central Nervous System; Depressive Disorder; Female; Glycols; Humans; Methoxyhydroxyphenylglycol; Middle Aged; Norepinephrine; Sympathetic Nervous System