In a 2005 study, fourteen currently depressed patients received acute tryptophan depletion (ATD) in a double-blind cross-over design. Different strengths of the ATD mixture were used on different days. Psychiatric symptoms were assessed at +6.5 hours and at +24 hours after ATD. Mood and psychiatric symptoms were improved, as was subjective sleep quality (Booij L, Van der Does AJ, Haffmans PM, Riedel WJ. J Affect Disord, 86(2): 305-11).

A 2002 study by Reidel, et al of the Behavior Institute at the University of Maastricht in the Netherlands examined the effects of the body's depletion of tryptophan on mood and cognitive function. They also measured how long the effects of the depletion lasted.

The experiments involved 27 volunteers, 16 of whom had an immediate relative with major depression. Researchers lowered the level of tryptophan in the volunteers' bodies, and memory tests showed impairment in their ability to recall and recognize words they learned during, but not before, the tryptophan depletion time period. However, the volunteers did better on focused attention tasks, concentrated listening tasks and tasks measuring the speed of memory retrieval.

The results also showed that tryptophan depletion induced mood depression in half of the subjects who had a family history of depression but in only 9 percent of those with no family history of depression. The latter finding suggests that people with depression in their families are more vulnerable to changes in serotonin levels. The mood depression effects ended within 24 hours in all of the volunteers, however.

"These findings may have implications for people who have a history of major depression in their families and people whose tryptophan becomes depleted because of dieting," the authors note. "They also may have implications for people whose tryptophan becomes depleted because they are undergoing immunotherapy for cancer” ( Riedel, W. et al. Brain, Behavior, and Immunity, Oct. 2002).

Acute tryptophan depletion in depressed patients treated with a selective serotonin-noradrenalin reuptake inhibitor: augmentation of antidepressant response?

Booij L, Van der Does AJ, Haffmans PM, Riedel WJ.

J Affect Disord. 2005 Jun;86(2-3):305-11

Department of Psychology, Leiden University, Wassenaarseweg 52, Leiden 2333 AK, The Netherlands.

BACKGROUND: It has frequently been demonstrated that experimental lowering of serotonin (5-HT) neurotransmission by acute tryptophan depletion (ATD) induces a transient depressed mood in 50-60% of patients treated with a selective serotonin reuptake inhibitor (SSRI) who are in remission from depression. In unmedicated depressed patients, ATD has no immediate effect on symptoms. The effects in currently depressed medicated patients have not been investigated. METHODS: Fourteen currently depressed patients (seven patients treated with a selective serotonin-noradrenalin reuptake inhibitor (SSNRI); seven other treatment, non-SSNRI) received ATD in a double-blind, crossover design. Different strengths of the ATD mixture (aimed at 50% and 90% reduction of tryptophan) were used on separate days. Psychiatric symptoms were assessed at both sessions prior to, at +6.5 h, and at +24 h after ATD. RESULTS: The ATD mixtures induced the expected reductions of plasma tryptophan levels. Full but not partial depletion improved mood and other psychiatric symptoms at +24 h in patients who received SSNRI treatment, as indicated by clinical ratings and self-report. Subjective sleep quality also improved. CONCLUSIONS: The effects of ATD on psychiatric symptoms in currently depressed patients are remarkably different from the results in recently remitted SSRI-treated patients. ATD in currently depressed patients treated with serotonergic antidepressants possibly provides important information about the mechanism of action of SSRIs.

PMID: 15935252 [PubMed - indexed for MEDLINE]

Tryptophan, mood, and cognitive function.

Brain Behav Immun. 2002 Oct;16(5):581-9

Riedel WJ, Klaassen T, Schmitt JA.

Experimental Psychopharmacology Unit, Brain & Behaviour Institute, Universiteit Maastricht, The Netherlands. willem.j.riedel@gsk.com

In separate experiments we investigated the duration of the effects of acute tryptophan depletion (ATD) on mood and cognition. The results showed that ATD's effects consist of lowering of mood only in subjects with a family history of unipolar depression. A specific impairment of memory consolidation was seen in all subjects. In subjects without any vulnerability for mood disorders, performance on so-called 'frontal tasks,' measuring higher attentional functions tended to improve after ATD. The effects of ATD on mood and cognition were manifest as long as biochemical indices of low tryptophan remained low. In conclusion, ATD is a model for impairment of memory, next to being a model of mood disorders in vulnerable subjects. Moreover, ATD could be used as a challenge to demonstrate individual vulnerability of the serotonergic system. Copyright 2002 Elsevier Science (USA)

PMID: 12401472 [PubMed - indexed for MEDLINE]

The effects of high-dose and low-dose tryptophan depletion on mood and cognitive functions of remitted depressed patients.

J Psychopharmacol. 2005 May;19(3):267-75

Booij L, Van der Does AJ, Haffmans PM, Riedel WJ, Fekkes D, Blom MJ.

Department of Psychology, Leiden University, Leiden, The Netherlands and Psychomedical Center Parnassia, The Hague, The Netherlands.

It has frequently been demonstrated that acute tryptophan depletion (ATD) induces a transient depressed mood in some patients who are in remission from depression. However, the effects of ATD on cognitive processes in remitted depressed patients have not been investigated. The aim of the present study was to investigate the effects of different extents of depletion on mood and cognitive tasks involving neutral and emotional stimuli. Twenty patients in remission or in partial remission from depression received ATD in a double-blind, crossover design. Mood was assessed at both sessions before, at +6.5 h and +24 h after depletion. Cognitive assessment in both sessions started at +4.75 h, and also before and after the whole procedure. The ATD mixtures induced the expected reductions of plasma tryptophan levels. High-dose ATD induced a depressive response in a subsample of patients and impaired the processing of positive information independent of mood change. Attention for neutral stimuli (Stroop interference) improved in a dose-dependent manner. ATD may affect mood and cognition via different pathways: one implicated in mood regulation and the processing of emotional information, and one for the processing of neutral information. The first pathway may be more important for discriminating vulnerability to impaired serotonin function. The comparison of the effects of high-dose and low-dose ATD is useful for those studies aiming to investigate the relationships among 5-HT, mood and cognition.

PMID: 15888512 [PubMed - indexed for MEDLINE]

The bovine protein alpha-lactalbumin increases the plasma ratio of tryptophan to the other large neutral amino acids, and in vulnerable subjects raises brain serotonin activity, reduces cortisol concentration, and improves mood under stress.

Am J Clin Nutr. 2000 Jun;71(6):1536-44

Markus CR, Olivier B, Panhuysen GE, Van Der Gugten J, Alles MS, Tuiten A, Westenberg HG, Fekkes D, Koppeschaar HF, de Haan EE.

TNO Nutrition and Food Research Institute, Zeist, The Netherlands. markus@voeding.tno.nl

BACKGROUND: Increased brain serotonin may improve the ability to cope with stress, whereas a decline in serotonin activity is involved in depressive mood. The uptake of the serotonin precursor, tryptophan, into the brain is dependent on nutrients that influence the cerebral availability of tryptophan via a change in the ratio of plasma tryptophan to the sum of the other large neutral amino acids (Trp-LNAA ratio). Therefore, a diet-induced increase in tryptophan availability may increase brain serotonin synthesis and improve coping and mood, particularly in stress-vulnerable subjects. OBJECTIVE: We tested whether alpha-lactalbumin, a whey protein with a high tryptophan content, may increase the plasma Trp-LNAA ratio and reduce depressive mood and cortisol concentrations in stress-vulnerable subjects under acute stress. DESIGN: Twenty-nine highly stress-vulnerable subjects and 29 relatively stress-invulnerable subjects participated in a double-blind, placebo-controlled study. Subjects were exposed to experimental stress after the intake of a diet enriched with either alpha-lactalbumin or sodium-caseinate. Diet-induced changes in the plasma Trp-LNAA ratio and prolactin were measured. Changes in mood, pulse rate, skin conductance, and cortisol concentrations were assessed before and after the stressor. RESULTS: The plasma Trp-LNAA ratio was 48% higher after the alpha-lactalbumin diet than after the casein diet (P = 0.0001). In stress-vulnerable subjects this was accompanied by higher prolactin concentrations (P = 0.001), a decrease in cortisol (P = 0.036), and reduced depressive feelings (P = 0.007) under stress. CONCLUSIONS: Consumption of a dietary protein enriched in tryptophan increased the plasma Trp-LNAA ratio and, in stress-vulnerable subjects, improved coping ability, probably through alterations in brain serotonin.

PMID: 10837296 [PubMed - indexed for MEDLINE]

The effects of nutrients on mood.

Public Health Nutr. 1999 Sep;2(3A):403-9.

Benton D, Donohoe RT.

Department of Psychology, University of Wales Swansea, Swansea, UK. d.benton@swansea.ac.uk

A recent major theory was that a meal high in carbohydrate increased the rate that tryptophan enters the brain, leading to an increase in the level of the neurotransmitter serotonin that modulates mood. Although such a mechanism may be important under laboratory conditions it is unlikely to be of significance following the eating of any typical meal. As little as 2-4% of the calories of a meal as protein will prevent an increased availability of tryptophan. Arguably the food with the greatest impact on mood is chocolate. Those who crave chocolate tend to do so when they feel emotionally low. There have been a series of suggestions that chocolate's mood elevating properties reflect 'drug-like' constituents including anandamines, caffeine, phenylethylamine and magnesium. However, the levels of these substances are so low as to preclude such influences. As all palatable foods stimulate endorphin release in the brain this is the most likely mechanism to account for the elevation of mood. A deficiency of many vitamins is associated with psychological symptoms. In some elderly patients folate deficiency is associated with depression. In four double-blind studies an improvement in thiamine status was associated with improved mood. Iron deficiency anaemia is common, particularly in women, and is associated with apathy, depression and rapid fatigue when exercising.

PMID: 10610080 [PubMed - indexed for MEDLINE]

Behavioral effects of dietary neurotransmitter precursors: basic and clinical aspects.

Neurosci Biobehav Rev. 1996 Summer;20(2):313-23

Young SN.

Department of Psychiatry, McGill University, Montreal, Quebec, Canada.

The levels and possibly function of several neurotransmitters can be influenced by the supply of their dietary precursors. The neurotransmitters include serotonin, dopamine, noradrenaline, histamine, acetylcholine and glycine, which are formed from tryptophan, tyrosine, histidine, choline and threonine. Tryptophan has been tested more than the other precursors in clinical trials and is currently available in some countries for the treatment of depression. Other uses for tryptophan and the therapeutic potential of other neurotransmitter precursors have not been tested adequately. Given the relative lack of toxicity of dietary components, further clinical trials with neurotransmitter precursors should be carried out.

PMID: 8811719 [PubMed - indexed for MEDLINE]