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Twenty-four hour urinary excretion of 3-methoxy-4-hydroxyphenyl-glycol (MHPG) was analyzed in 48 unipolar and 19 bipolar depressed patients and 16 healthy controls. All patients were interviewed using the Schedule for Affective Disorders and Schizophrenia. Various symptoms and descriptive variables were correlated univariately with urinary MHPG in two random groups, and those items showing a trend in both splits were further reduced by a multiple regression technique, first on each split separately and finally on the pooled sample. Urinary MHPG correlated significantly both in uni- and multivariate tests with age (positively, but only in females), altered motor activity (summed scores of agitation and retardation during the worst week of present or recent depression), and with existence of at least one suicide attempt before the present depressive episode (last items negatively). There were no differences between unipolar and bipolar patients, or between any patient group and the healthy controls. Males excreted about 25% more MHPG than females. Levels of MHPG in urine and cerebrospinal fluid were highly significantly intercorrelated.

In order to evaluate the presumed involvement of altered noradrenergic receptor sensitivity in the switch process from depression into mania, we explored the relationship between pretreatment 3-methoxy-4-hydroxy-phenylglycol (MHPG) and tricyclic-induced mania or hypomania in bipolar depressed patients. Within the group of patients developing mania or hypomania on tricyclics, there was a strong positive correlation between pretreatment 24-hour urinary MHPG and the latency of onset of the episode. This finding is consistent with both the reported differences in MHPG excretion between unipolar and bipolar patients and the postulated noradrenergic involvement in the switch process.

Higher levels of homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) were observed in urines of 12 premature infants than in older children. An examination of the influence of age, sex, size, and head circumference revealed that the smaller the infants, the higher the HVA and MHPG values. Recently several investigators have reported an increased titer of urinary HVA in autistic children. It has been hypothesized that the increased levels of catecholamine metabolites (notable HVA and MHPG) could reflect accelerated catecholamine turnover. The elevated urinary HVA titers in infants as well as in autistic children may be due to an immaturity of the dopaminergic receptors.

3-Methoxy-4-hydroxyphenylethyleneglycol (MHPG) was measured in 24-hour urine collections obtained from 44 drug-free patients hospitalized for a major depressive disorder, MHPG was significantly lower in a group of three biopolar 1 patients than in a group of unipolar patients. The excretion of MHPG did not significantly differ among patients classified as psychoatic, agitated, or retarded subtypes of depression as compared to patients not assigned to these subtypes.

Levels of 24-hour urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) were not markedly elevated in a group of 35 panic disorder patients when compared to healthy controls (mean = 2,430 micrograms/day vs. 2,130 micrograms/day). There was a weak association between elevated pretreatment levels of MHPG and a positive treatment response to alprazolam or diazepam. Alprazolam and diazepam may differ in their effects on MHPG.

Urinary 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) excretion was determined in rats after central noradrenergic pathway interruption by ventral bundle transection or by locus coeruleus (LC) lesions. The transection prevented an increase in urinary MHPG that occurred in sham-operated animals, an effect that was presumed to be due to loss of cerebrospinal fluid (CSF). Electrolytic lesioning of the LC, which was not attended by loss of CSF, had no effect on baseline MHPG excretion but diminished the response to subsequent administration of the alpha-adrenergic blocking agent, phenoxybenzamine (PBZ). Since the contribution of brain MHPG to total urinary MHPG is small, the observed effects of these procedures are most likely due to disrupted central regulation of peripheral sympathetic nerve activity.

The results of the dexamethasone suppression test (DST) were compared to levels of 24-hour 3-methoxy-4-hydroxyphenylglycol (MHPG) in 60 patients with unipolar depression. DST nonsuppressors had significantly higher levels of MHPG than did DST suppressors. The possible implications of this finding are discussed.

The relationship between urinary excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG) and overt behaviors emitted in two hospital environments was examined in a group of 27 drug-free psychiatric patients. Depressed patients with high MHPG excretion ate less and engaged in less visual activity in the lunch environment. Schizophrenic patients but not depressive patients with high MHPG tended to have greater body activity during the gym environment. The implications of these findings for the identification of subtypes of depression and schizophrenia, and for an improved methodology in investigation of biobehavioral relations in clinical populations, are discussed.

Measures of daily urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) excretion and electroencephalographic (EEG) sleep data were examined in 30 patients hospitalized for depression. This sample (mean age = 35 years) comprised 17 females and 13 males, all of whom were drug-free for 2 weeks and met Research Diagnostic Criteria for primary depressive disorder. Data analyses were conducted on the entire group, as well as the male, female, unipolar, and recurrent subgroups. No significant relationships were observed between total MHPG excretion and rapid eye movement (REM) or non-REM sleep variables. In particular, the absence of an interrelatedness of MHPG and REM sleep fails to confirm earlier findings in a smaller patient sample. These results, therefore, raise new questions about the proposed role of central noradrenergic activity in the mediation of REM sleep in depression.

Twenty-five men and 26 women with major unipolar depression were evaluated by the TRH test and urinary MHPG excretion. A significant positive correlation between TSH response to TRH and urinary MHPG was found in the men, though not in the women. These findings suggest that at least for depressed men, central norepinephrine deficiency may be the neurobiological substrate of blunted TSH responses to TRH.

Unlabelled: Reported mean values for urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) for both depressed patients and controls vary substantially between laboratories. The present study describes methodological sources of variance affecting urinary MHPG values. Although intra-assay variance is small (coefficient of variation (CV) = 4.6%), the interassay variance is high (CV = 14.3%) and suggests caution in the interpretation of small group differences. The gas chromatographic (GC) method in this laboratory produces values highly correlated (r = 0.98) with those obtained by a reference gas chromatographic-mass spectrometric (GC-MS) method. The absolute values obtained by GC are 20% higher than those by GC-MS--a problem that may be shared to a varying extent by all GC assays., In Conclusion: methodological differences do contribute to some of the variation in reported values of urinary MHPG.

Anxiety may be associated with increased norepinephrine activity. Urinary levels of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) were examined in depressed patients with and without panic attacks. Depressed patients with panic attacks had significant elevations of MHPG.

To investigate the interrelationships between the noradrenergic and serotonergic systems and the hypothalamic-pituitary-adrenal (HPA) axis, we measured the excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG) and free cortisol (UFC) in 24-h urine both before and after loading with 2 g L-tryptophan (L-TRP) orally in 24 healthy controls and 33 depressed patients categorized according to DSM-III. Loading with L-TRP reduced MHPG excretion significantly by 56% in major depressives, whereas in healthy controls and in minor depressives no significant effects were observed. Although basal MHPG did not differ among these study groups, loading with L-TRP resulted in MHPG excretion in major depressives being significantly lower than in healthy controls and minor depressives. Loading with L-TRP increased UFC significantly by 49% only in major depressives with associated features. After L-TRP those patients exhibited significantly increased UFC as compared with all other depressives and controls, whereas basal UFC values did not differ among the study groups. In baseline conditions there were no significant correlations between MHPG and UFC excretion.