CSF neurochemicals during tryptophan depletion in individuals with remitted depression and healthy controls

Abstract

The purpose of this study was to examine the differential effects of acute tryptophan (TRP) depletion vs. sham condition on plasma, cerebrospinal fluid (CSF) biochemical parameters, and mood in the following three subject groups: (1) nine antidepressant-free individuals with remitted depression, (2) eight paroxetine-treated individuals with recently remitted depression, and (3) seven healthy controls.Plasma TRP decreased during TRP depletion and increased during sham condition (p<.01). CSF TRP and 5-hydroxyindoleacetic acid were lower during TRP depletion than sham condition (p<.01 each). During TRP depletion, CSF TRP correlated significantly with the plasma sum of large neutral amino acids (ΣLNAA) (R= −.52, p=.01), but did not significantly correlate with plasma TRP (R= .15, p= . 52). The correlation between CSF TRP and ratio of TRP to ΣLNAA was (R= .41, p=.06) during TRP depletion, and (R= −.44, p=.04) during sham condition. A negative correlation trend was observed between CSF TRP levels and peak Hamilton Depression Rating Scale scores during TRP depletion in patients recovered from depression (R= −.45, p=.07), but not in healthy controls (R= −.01, p= . 98). CSF Neuropeptide Y was higher during TRP depletion than sham condition (t= 1.75, p < .10).These results illustrate the importance of assessing plasma ΣLNAA when using the TRP depletion paradigm. The use of a single CSF sampling technique although practical may result in data acquisition limitations.

The Effects of Acute Tryptophan Depletion on Brain Activation During Cognition and Emotional Processing in Healthy Volunteers

“…[5]), and reduces plasma TRP, plasma ratio TRP/LNAA, TRP and 5-hydroxyindoleaceticacid (5-HIAA; 5-HT metabolite) levels in cerebrospinal fluid (e.g. [107]), and synthesis of brain 5-HT in humans [12]. However, these measures are only estimates for the 5-HT neuronal activity.…”

Acute tryptophan depletion in humans: a review of theoretical, practical and ethical aspects

“…The lowering of sero tonin synthesis after ATD had been confirmed in several studies that demonstrated a lowering of 5-HIAA in the CSF of volunteers undergoing ATD. 15,[17][18][19][20] Recently, van Donkelaar and colleagues 21 suggested that "direct evidence that ATD decreases extracellular [serotonin] concentrations is lacking" and that "several studies provide support for alternative underlying mechanisms of ATD." While this has been challenged by Crockett and colleagues, 22 these are important issues that need to be discussed further, as all relevant issues were not discussed in these 2 papers.…”

“…After ATD, there is a correlation between plasma trp/∑LNAA, but not plasma tryptophan, and the level of the serotonin metabolite 5-HIAA in the CSF. 15 Nishizawa and colleagues 16 used PET, with α-[ 11 C]methyl-Ltryptophan as a tracer, to study the rate of serotonin synthesis after ATD in healthy volunteers. In all brain regions measured, the decline in serotonin synthesis was greater than 85% and was greater in women than in men.…”

In psychiatrically healthy individuals, overweight women but not men have lower tryptophan levels

“…In contrast, obese men had 37% lower odds of having had depression in the past year than normal-weight men. Individuals with depression have lower plasma TRP levels [21] and, hence, lower central nervous system (CNS) serotonin levels [22,23], which are associated with depression [24]. Experimental TRP depletion studies confirm the depressogenic role of lowering TRP [25–31].…”