Decrease in plasma levels of 3,4-dihydroxyphenylethyleneglycol in major depression

Abstract

Plasma levels of free and sulfoconjugated 3,4-dihydroxyphenylethyleneglycol (DOPEG), the main deaminated metabolite of norepinephrine, were measured in a group of 45 hospitalized patients presenting a major depression and a group of 45 healthy subjects, matched for sex and age. Compared to healthy subjects, depressed patients had significantly lower plasma levels of free and sulfoconjugated DOPEG. The ratio of free over conjugated DOPEG was not statistically different in the two groups. The reduction of plasma DOPEG levels in the depressed patients did not appear to be related to the duration of drug-free period and was similar in males and females. There was no statistically significant correlation between plasma DOPEG levels and total score on the Hamilton Rating Scale for Depression. Finally, plasma DOPEG levels did not differ in unior bipolar patients. The present data provides further evidence for a reduced CNS noradrenergic transmission in major depression.

Plasma 3,4-Dihydroxyphenylethyleneglycol and 3-Methoxy-4-Hydroxyphenylethyleneglycol as Indicators of Central Noradrenergic Activity

“…In respect of the influence of the sex, our results are in agreement with those of Scatton et al [ 1986], while Loo et al [1983] found that in healthy people only free and total plasma DOPEG were higher in women than in men. As for MOPEG, our results are in agreement with those of Jimerson et al [1981a] and Halbreich et al [1987], In the present experiments, age did not seem to influence the plasma concentration of DOPEG in de pressive patients, as Loo et al [1983] found, while Scatton et al [ 1986] described a positive correlation between free DOPEG and age.…”

“…As in the previous studies on DOPEG using a differ ent method of measurement, a significant decrease in the plasma levels was noted in depressed patients compared with the control subjects whatever the type or clinical form of the depression [Loo et al, 1983[Loo et al, , 1985Scatton et al, 1986].…”

“…Recent publications [Loo et al, 1983[Loo et al, , 1985[Loo et al, , 1986aRobinson et al, 1983;Scatton et al, 1986] indicate interest in measurement of the plasma concentra tion of 3,4-dihydroxyphenylethyleneglycol (DHPG or DOPEG), whose changes in the brain are said to reflect the modifications of the noradrenergic metabolism as well as if not better than MOPEG [Stone, 1975[Stone, , 1976Braestrup and Nielsen, 1976;Nielsen and Braestrup, 1977;Scatton, 1982], Its level might be significantly lower in depressive patients [Loo et al, 1983[Loo et al, , 1985Scatton et al, 1986] but its value in treatment seems unlikely in relation to the choice of a specific tricyclic drug [Loo et al, 1986b], DOPEG, formed in the nerve endings by oxidative deamination through the action of a type A monoamine oxidase (MAO-A) after the reuptake of norepinephrine (NE), leads to the formation of MOPEG through a catechol-O-methyltransferase (COMT) in the synaptic cleft. Another pathway, entirely extraneuronal, is known to exist for the degradation of NE resulting in the forma tion of MOPEG after the successive action of a COMT and a MAO-A.…”

Lack of circadian rhythm in plasma levels of 3,4-dihydroxyphenylethyleneglycol in healthy human subjects

“…Another point which deserves some comment is the fact that the concentrations of plasma sulfate-conjugated, but not free DOPEG (P>0.1) in the volunteers participating in this study are significantly lower (P < 0.001) than normal levels previously reported (Scatton et al 1986). It is thus possible that non-specific factors such as diet or physical effort can influence plasma sulfate-conjugated DOPEG levels.…”

“…We have recently shown that plasma free and conjugated DOPEG levels are significantly lower in depressed patients compared to normal volunteers (Scatton et al 1986). These subnormal levels of the noradrenaline metabohte would be consistent with the monoamine hypothesis of affective disorders which postulates that some forms of depression are associated with a deficiency of cerebral noradrenergic transmission (Schildkraut 1965;Maas 1975;Garver and Davis 1979).…”