Tryptophan depletion causes a rapid lowering of mood in normal males

Abstract

Normal male human subjects ingested amino acid mixtures which were tryptophan-free, balanced or contained excess tryptophan. The tryptophan-free mixture causes a marked depletion of plasma tryptophan by 5 h. At this time the subjects in the tryptophan-free group had significantly elevated scores on the depression scale of the Multiple Affect Adjective Checklist. The tryptophan-free group also performed worse than the other two groups in a proofreading task carried out while listening to a tape with themes of hopelessness and helplessness (dysphoric distractor). Cognitive theories of depression predict greater distractability of depressed individuals by dysphoric themes. Thus, both measures indicate a rapid mood lowering effect of tryptophan depletion in normal males. This effect is probably mediated by a lowering of brain 5-hydroxytryptamine. Although the mood-lowering effect was not as great as that seen in depressed patients, our results suggest that low brain 5HT might be one factor precipitating depression in some patients.

Acute Tryptophan Depletion in Healthy Volunteers Enhances Punishment Prediction but Does not Affect Reward Prediction

“…There is abundant empirical evidence implicating 5-HT in controlling aversion and potentiating anxiety-induced avoidance (Tye et al, 1977;Gray, 1982;Graeff et al, 1996). The hypothesis concurs with the observation that serotonergic neurotransmission is implicated in a range of mood and anxiety disorders (Young et al, 1985;Anderson et al, 1990;Deakin et al, 1990;Blier and de Montigny, 1999) that are characterized by enhanced anticipation of, and sensitivity to threat-related stimuli, punishment, and negative feedback (Beats et al, 1996;Elliott et al, 1997;Mathews and Mackintosh, 2000;Steffens et al, 2001;Richards et al, 2002;Murphy et al, 2003). Studies with healthy human volunteers have demonstrated potentiated processing of punishment-related signals after dietary depletion of the 5-HT precursor tryptophan (TRP; acute tryptophan depletion, ATD), particularly in vulnerable individuals.…”

Differential Effects of Acute Serotonin and Dopamine Depletion on Prepulse Inhibition and P50 Suppression Measures of Sensorimotor and Sensory Gating in Humans

“…Before each testing session, participants were required to adhere to a 24-h low-protein diet, with their total protein consumption to be less than 20 g (Young et al, 1985;Harrison et al, 2004). Participants were also required to fast from 1900 hours the evening before each testing day, with the exception of drinking water.…”

“…The amino-acid composition for the depletion treatments was based on the 104 g balanced mixture developed by Young et al (1985), and modified for the CMD as outlined by Nathan et al (2004). In the current study, the amino-acid mixture for the balanced control treatment consisted of 5.5 g of L-alanine, 3.2 g of glycine, 3.2 g of L-histidine, 8.0 g of L-isoleucine, 13.5 g of leucine, 11.0 g of L-lysine monohydrochloride, 5.7 g of L-phenylalanine, 12.2 g of L-proline, 6.9 g of L-serine, 6.5 g of L-threonine, 2.3 g of L-tryptophan, 6.9 g of L-tyrosine, and 8.9 g of L-valine.…”

Decreasing Amphetamine-Induced Dopamine Release by Acute Phenylalanine/Tyrosine Depletion: A PET/[11C]Raclopride Study in Healthy Men

“…They then ingested one of the AA mixtures given in counter-balanced order. The APTD mixture's composition, preparation, and administration is based on our 100 gm nutritionally balanced mixture with phenylalanine and tyrosine withheld (Young et al, 1985;Leyton et al, 2000b). Following ingestion of the mixture, participants remained awake in a room with videos, television, and reading material available to them.…”