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

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

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