Suppressant effects of dexamethasone on the availability of plasma L‐tryptophan and tyrosine in healthy controls and in depressed patients

Abstract

Formation in the brain of serotonin from L-tryptophan (L-TRP) and noradrenaline from tyrosine are pathways related to the pathophysiology of major depression and to the regulation of the hypothalamic-pituitary-adrenal (HPA) axis. In the past, decrements in L-TRP availability and disorders in the HPA axis have repeatedly been observed in major depressed patients; both factors were shown to be inversely correlated. In order to investigate the relationships between glucocorticosteroid activity and the availability of L-TRP and tyrosine, the authors measured L-TRP, tyrosine, valine, leucine, isoleucine and phenylalanine in baseline conditions and after treatment with 1 mg dexamethasone in 16 healthy controls and in 50 depressed patients. The ratios between L-TRP and tyrosine and the sums of the amino acids known to compete with them during transport across the blood-brain barrier were computed as an index of (respectively) the serotonin and noradrenaline synthesis in the brain. We found significantly decreased plasma L-TRP and tyrosine levels after treatment with dexamethasone compared with basal levels. Accordingly, the plasma ratios between L-TRP and tyrosine and the sum of the competing amino acids were significantly reduced by dexamethasone administration. It was hypothesized that through these actions of dexamethasone on peripheral amino acids, the central noradrenaline and serotonin control over the HPA-axis could be altered.

Role of serotonergic and noradrenergic systems in the pathophysiology of depression and anxiety disorders

“…As with NE, indirect measures of precursor availability and metabolite concentrations provided initial evidence for abnormalities in the system. There are several reports that plasma tryptophan availability is significantly lower in patients with major depression when compared to normal controls [Maes et al, 1990;Deakin et al, 1990]. Although there have been numerous findings of decreased 5HIAA in plasma and CSF in depression [Asberg et al, 1976;Roy et al, 1989], discordant results have also been obtained over the years [Maes and Meltzer, 1995].…”

Differential Effects of 5-HTTLPR Genotypes on Inhibition of Negative Emotional Information Following Acute Stress Exposure and Tryptophan Challenge

“…Among the various biochemical processes involved, brain serotonin (5-HT) dysfunction appears to be a meaningful risk factor (Maes and Meltzer, 1995;Van Praag, 2004). 5-HT dysfunction manifests in depressed patients as lowered brain tryptophan (TRP) concentrations (eg, see Agren and Reibring, 1994;Maes et al, 1990); impaired 5-HT synthesis, release, reuptake, or metabolism (eg, see Maes and Meltzer, 1995;Malison et al, 1998;van Praag et al, 1970); or 5-HT receptor disturbances (eg, see Cowen et al, 1994;Sargent et al, 2000), whereas antidepressant drugs generally act by improving brain 5-HT function (Delgado et al, 1990;Delgado et al, 1993;Maes and Meltzer, 1995). 5-HT dysfunction in depression is promoted by a genetic vulnerability involving a polymorphism in the 5-HT transporter-linked promoter region .…”

Differential Effects of Tri-Allelic 5-HTTLPR Polymorphisms in Healthy Subjects on Mood and Stress Performance After Tryptophan Challenge

“…Among the neurochemical processes involved, reduced brain serotonin (5-HT) function seem to be a relevant pathophysiological mechanism involved (Maes and Meltzer, 1995;Van Praag, 2004). Although there are still open questions about the exact involvement of 5-HT in the onset and course of depression, 5-HT dysfunction is commonly indicated in depressed patients by lower brain availability of tryptophan and 5-hydroxytryptophan (5-HTP) (Agren and Reibring, 1994;Maes et al, 1990); impaired 5-HT synthesis, release, reuptake, or metabolism (Maes and Meltzer, 1995;Malison et al, 1998;van Praag et al, 1970); or 5-HT receptor disturbances (Cowen et al, 1994;Sargent et al, 2000). In addition, antidepressant drugs mainly act by improving brain 5-HT function (Delgado et al, 1990;Delgado et al, 1993;Maes and Meltzer, 1995).…”