Indolic Substances in Plasma, Cerebrospinal Fluid, and Frontal Cortex of Human Subjects Infused with Saline or Tryptophan

Abstract

Psychiatric patients undergoing the psychosurgical operation of stereotactic subcaudate tractotomy were infused intravenously with either saline or L-tryptophan (15 mg/kg/h). Plasma, lumbar cerebrospinal fluid (CSF), ventricular CSF and a specimen of frontal cortex were collected. The relationships of plasma concentrations of substances claimed to influence brain tryptophan concentration (total tryptophan, free tryptophan, large neutral amino acids) with the concentration of tryptophan in the cortex and CSF were investigated. Tryptophan infusion resulted in plasma tryptophan values comparable to those found after oral doses used in treating depression or insomnia, and about sixfold increases of tryptophan in the cerebral cortex. Increased brain 5-hydroxytryptamine synthesis was indicated by significant rises of CSF 5-hydroxyindoleacetic acid. The concentration of plasma free tryptophan was a better predictor than plasma total tryptophan of cortex tryptophan concentration. As all correlation coefficients of plasma versus brain or plasma versus ventricular CSF tryptophan concentrations were decreased when allowance was made for differences of concentration of large neutral amino acids, the results suggest that the role of these substances within their physiological range as inhibitors of tryptophan transport to the brain may previously have been overemphasised.

Plasma and CSF tryptophan in cancer anorexia

“…Both in cancer patients and controls CSF tryptophan levels were directly correlated with the ratio in plasma free tryptophan/competing large neutral amino acids, whereas a less significant correlation was found with plasma free tryptophan levels. These data, although not in contrast, do not confirm those reported by Gillman (Gillman et al, 1981) indicating plasma free tryptophan as best predictor for cortex tryptophan concentrations. Nevertheless from the present study it must be concluded that the significant rise in CSF tryptophan levels observed in the presence of cancer anorexia should be mainly ascribed to a consistent modi-fication in plasma of the ratio between tryptophan and the sum of its competing amino acids for the passage across the blood-brain barrier.…”

Differences between males and females in rates of serotonin synthesis in human brain

“…In rat brain under steady-state conditions, we reported a substantial diffusion component for the blood-brain transfer of tryptophan (42). What evidence there is from human CSF studies suggests that other large neutral amino acids reduce, as in experimental animals, tryptophan uptake into human brain (43)(44)(45).…”

Kinetic Compartment Modeling of [11C]-5-Hydroxy-L-Tryptophan for Positron Emission Tomography Assessment of Serotonin Synthesis in Human Brain

“…On the other hand, if diffusion prevails, it is sufficient to evaluate the protein-free plasma Trp concentration to obtain an estimate of the brain tissue concentration. Indeed, the latter approach has been shown to yield the best correlations, as shown by Gillman et al (1981), who assessed plasma and brain tissue Trp levels in fasting schizophrenic patients before brain surgery. In accordance with these results, we found trends towards positive, linear relations between k 3 values, averaged across the 12 investigated brain regions, and both the K m -normalized Trp ratio and the protein-free Trp plasma concentration.…”