Tryptophan Depletion Alters the Decision-Making of Healthy Volunteers through Altered Processing of Reward Cues Effects of oral 5-hydroxy-tryptophan on energy intake and macronutrient selection in non-insulin dependent diabetic patients Effects of normal meals rich in carbohydrates or proteins on plasma tryptophan and tyrosine ratios. Effects of tryptophan depletion vs catecholamine depletion in patients with seasonal affective disorder in remission with light therapy. An index of 5-HT synthesis changes during early antidepressant treatment: α-[11C]methyl-l-tryptophan PET study
While accumulating evidence suggests that effective real-life decision-making depends upon the functioning of the orbitofrontal cortex , much less is known about the involvement of the monoamine neurotransmitter systems and , in particular , serotonin . In the present study , we explored the impact of depleting the serotonin precursor , tryptophan , on human decision-making . Eighteen healthy volunteers consumed an amino-acid drink containing tryptophan and 18 healthy volunteers consumed an amino-acid drink without tryptophan , before choosing between simultaneously presented gambles , differing in the magnitude of expected gains ( ie reward ) , the magnitude of expected losses ( ie punishment ) , and the probabilities with which these outcomes were delivered . Volunteers also chose between gambles probing identified non-nomative biases in human decision-making , namely , risk-aversion when choosing between gains and risk-seeking when choosing between losses . Tryptophan-depleted volunteers showed reduced discrimination between magnitudes of expected gains associated with different choices . There was little evidence that tryptophan depletion was associated with altered discrimination between the magnitudes of expected losses , or altered discrimination between the relative probabilities with which these positive or negative outcomes were delivered . Risk-averse and risk-seeking biases were also unchanged . These results suggest that serotonin mediates decision-making in healthy volunteers by modulating the processing of reward cues , perhaps represented within the orbitofrontal cortex . It is possible that such a change in the cognition mediating human choice is one mechanism associated with the onset and maintenance of anhedonia and lowered mood in psychiatric illness OBJECTIVE : In obese patients , brain serotonergic stimulation via orally administered 5-hydroxy-tryptophan ( 5-HTP ) , the precursor of serotonin , causes decreased carbohydrate intake and weight loss . Since diabetes mellitus is associated with depressed brain serotonin , hyperphagia and carbohydrate craving , we hypothesized that in diabetic patients , orally administered 5-HTP stimulates brain serotonergic activity and thus normalizes eating behaviour . To test this hypothesis , we investigated whether in diabetic patients : 1 ) predicted brain serotonin concentrations are depressed as a result of decreased availability of the precursor , tryptophan ; and 2 ) oral 5-HTP is effective in reducing energy and carbohydrate intake . SUBJECTS AND METHODS : 25 overweight non-insulin dependent diabetic out patients were enrolled in a double-blind , placebo-controlled study , and r and omized to receive either 5-HTP ( 750 mg/d ) or placebo for two consecutive weeks , during which no dietary restriction was prescribed . Energy intake and eating behaviour , as expressed by macronutrient selection , were evaluated using a daily diet diary . Plasma amino acid concentrations and body weight , as well as serum glucose , insulin and glycosylated haemoglobin were assessed . RESULTS : 20 patients ( nine from the 5-HTP group and 11 from the Placebo group ) completed the study . Brain tryptophan availability in diabetic patients was significantly reduced when compared to a group of healthy controls . Patients receiving 5-HTP significantly decreased their daily energy intake , by reducing carbohydrate and fat intake , and reduced their body weight . CONCLUSIONS : These data confirm the role of the serotonergic system in reducing energy intake , by predominantly inhibiting carbohydrate intake , and suggest that 5-HTP may be safely utilized to improve the compliance to dietary prescriptions in non-insulin dependent diabetes mellitus BACKGROUND The delivery of circulating tryptophan to the brain and its conversion to serotonin vary directly with plasma concentrations of tryptophan and inversely with those of other large neutral amino acids ( LNAAs ) . Although carbohydrate-rich , protein-free formula diets have been shown to elevate , and high-protein diets to depress , the tryptophan-LNAA ratio , few data are available about this ratio 's responses to actual meals . OBJECTIVE We determined whether carbohydrate-rich or protein-rich breakfasts , such as those Americans normally eat , produce substantial differences in the plasma tryptophan-LNAA ratio and in the corresponding ratio for tyrosine , the precursor of brain dopamine and norepinephrine . DESIGN Nine overnight-fasted subjects consumed , 3 - 7 d apart , a carbohydrate-rich ( 69.9 g carbohydrate and 5.2 g protein ) and a protein-rich ( 15.4 g carbohydrate and 46.8 g protein ) breakfast . Blood sample s collected at baseline and after 40 , 80 , 120 , and 240 min were assayed for tryptophan , tyrosine , the 5 other LNAAs , and insulin . RESULTS The carbohydrate-rich and protein-rich breakfasts had significantly different effects on both the plasma tryptophan-LNAA and tyrosine-LNAA ratios ( each P < 0.01 ) . Among the 8 subjects who consumed both breakfasts , the median difference for tryptophan : LNAA was 54 % ( range : 36 - 88 % ) and for tyrosine : LNAA was 28 % ( range : 10 - 64 % ) . Insulin concentrations rose significantly after the carbohydrate but not after the protein meal . CONCLUSIONS High-carbohydrate and high-protein breakfasts similar to those Americans normally eat can cause substantial differences in the plasma tryptophan ratio and thus , probably , in brain tryptophan concentrations and serotonin synthesis . Such meals also change the plasma tyrosine ratio and may thereby modify catecholamine synthesis BACKGROUND Although hypotheses about the therapeutic mechanism of action of light therapy have focused on serotonergic mechanisms , the potential role , if any , of catecholaminergic pathways has not been fully explored . METHODS Sixteen patients with seasonal affective disorder who had responded to a st and ard regimen of daily 10000-lux light therapy  were enrolled in a double-blind , placebo-controlled , r and omized crossover study . We compared the effects of tryptophan depletion with catecholamine depletion and sham depletion . Ingestion of a tryptophan-free amino acid beverage plus amino acid capsules was used to deplete tryptophan . Administration of the tyrosine hydroxylase inhibitor alpha-methyl-paratyrosine was used to deplete catecholamines . Diphenhydramine hydrochloride was used as an active placebo during sham depletion . The effects of these interventions were evaluated with measures of depression , plasma tryptophan levels , and plasma catecholamine metabolites . RESULTS Tryptophan depletion significantly decreased plasma total and free tryptophan levels . Catecholamine depletion significantly decreased plasma 3-methoxy-4-hydroxyphenylethyleneglycol and homovanillic acid levels . Both tryptophan depletion and catecholamine depletion , compared with sham depletion , induced a robust increase ( P<.001 , repeated- measures analysis of variance ) in depressive symptoms as measured with the Hamilton Depression Rating Scale , Seasonal Affective Disorder Version . CONCLUSIONS The beneficial effects of light therapy in the treatment of seasonal affective disorder are reversed by both tryptophan depletion and catecholamine depletion . These findings confirm previous work showing that serotonin plays an important role in the mechanism of action of light therapy and provide new evidence that brain catecholaminergic systems may also be involved The antidepressant selective serotonin transporter inhibitors ( SSRIs ) are clinical ly active after a delay of several weeks . Indeed , the rapid increase of serotonin ( 5-HT ) caused by SSRIs , stimulates the 5-HT(1A ) autoreceptors , which exert a negative feedback on the 5-HT neurotransmission . Only when autoreceptors are desensitized , can SSRIs exert their therapeutic activity . The 5-HT(1A ) receptor antagonist pindolol has been used to accelerate the clinical effects of antidepressant by preventing the negative feedback . Using the alpha-[(11)C]methyl-L-tryptophan/positron emission tomography ( PET ) , the goal of the present double-blind , r and omized study was to compare the changes in alpha-[(11)C]methyl-L-tryptophan trapping , an index of serotonin synthesis , in patients suffering from unipolar depression treated with the SSRI citalopram ( 20 mg/day ) plus placebo versus patients treated with citalopram plus pindol ( 7.5 mg/day ) .  PET and Hamilton depression rating scale ( HDRS-17 ) were performed at baseline , and after 10 and 24 days of antidepressant treatment . Results show that the combination citalopram plus pindol , compared to citalopram alone shows a more rapid and greater increase of an index of 5-HT synthesis in prefrontal cortex ( BA 9 ) . This research is the first human PET study demonstrating that , after 24 days , the combination SSRIs plus pindolol produces a greater increase of the metabolism of serotonin in the prefrontal cortex , an area associated to depressive symptoms
Graphical abstract Excessive dieting‐induced nutritional deficiency of tryptophan : Effects on behavior and efficacy of antipsychotic and antidepressant medication .
& NA ; A growing body of evidence suggests that our diet is an important contributing factor in the development , management and prevention of a number of psychiatric illnesses .
Tryptophan , an essential amino acid , is the sole precursor of neurotransmitter 5‐hydroxytryptamine ( 5‐HT ; serotonin ) .
Administration of tryptophan can boost serotonin neurotransmission to produce therapeutically important effects in serotonin deficiency disorders .
Anorexia nervosa ( AN ) an eating disorder associated with high levels of psychiatric comorbidity including psychosis , hyperactivity , depression and anxiety has highest lethality of all psychiatric illnesses .
Evidence suggests that excessive dieting and food restriction can decrease brain tryptophan and serotonin in AN patients to precipitate depression , psychosis and hyperactivity .
There are currently no FDA approved pharmacological treatments available for AN patients ; antidepressants and antipsychotics , largely used to treat associated psychiatric comorbidities are also not very effective .
The aim of this non‐ systematic review article is to evaluate and document a potential importance of tryptophan supplementation in improving therapeutics in AN patients .