Behavioural effects of acute tryptophan depletion in healthy male volunteers

Abstract

Acute tryptophan depletion (ATD) studies have been used to assess the role of the serotonergic system in various aspects of human behaviour. Changes in mood have already been described in selected groups of individuals submitted to ATD. The present study was a randomized, double-blind, cross-over trial designed to evaluate the effects of ATD on mood, memory, attention and induced anxiety in normal male volunteers. Twelve healthy male volunteers were submitted to two separate sessions of ATD, 1 week apart. Drinks containing either a balanced mixture of amino acids (B) or a similar mixture devoid of tryptophan (T–) were administered in each session. Mood was assessed using self-rating scales. Attention and memory were assessed using a battery of psychological tests. Anxiety induction was carried out using a simulation of public speaking. Blood levels of tryptophan were assessed before and after the B and T– drinks. Results showed that ATD markedly decreased plasma tryptophan (p< 0.0001). Mood ratings, memory and attention were not changed by the T– drink. There was no difference among the anxiety levels measured under T– or B mixtures. These data supports the notion that ATD does not change mood and cognitive function in healthy subjects.

Keywords

acute tryptophan depletion anxiety attention memory mood serotonin simulated public speaking

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References

Bond A , Lader M (1974) The use of analogue scales in rating subjective feelings. Br J Psychol 47: 211–218

Coull J T , Sahakian B J , Middleton H C , Young A H , Park S B , McShane R H Cowen P J, Robbins T W (1995) Differential effects of clonidine, haloperidol, diazepam and tryptophan depletion and focused attention and attentional search. Psychopharmacology 121: 222–230

Delgado P L , Charney D S , Price L H , Aghajanian G K , Landes H , Heninger G R (1990) Serotonin function and the mechanism of antidepressant action: reversal of antidepressant-induce remission by rapid depletion of plasma tryptophan. Arch Gen Psychiatry 47: 411–419

Ellenbogen M A , Young S N , Dean P , Palmour R M , Benkelfat C (1996) Mood response to acute tryptophan depletion in healthy volunteers: sex differences and temporal stability. Neuropsychopharmacology 15: 465–474

Higgit A , Lader M , Fonagy P (1986) The effects of the benzodiazepine antagonists RO 15–1788 on psychophysiological performance and subjective measures in normal subjects. Psychopharmacology 89: 395–403

Kapczinski F , Curran H V , Gray J , Lader M (1994) Flumazenil has an axiolytic effect in simulated stress. Psychopharmacology 114: 187–189

Klaassen T , Klumperbeek J , Deutz N E , van Praag H M , Griez E (1998) Effects of tryptophan depletion on anxiety and on panic provoked by carbon dioxide challenge. Psychiatry Res 77: 167–174

Klaassen T , Riedel W J , Deutz N E , van Someren A , van Praag H M (1999) Specificity of the tryptophan depletion method. Psychopharmacology 141: 279–286

Lezak M D (1995) Neuropsycological assessment, 3rd edn. Oxford University Press, New York

10.

Majdan A , Sziklas V , Jones-Gotman M (1996) Performance of healthy subjects and patients with resection from the anterior temporal lobe on matched tests of verbal and visuoperceptual learning. J Clin Exp Neuropsychol 18: 416–430

11.

McNair D M , Frankenthaler L M , Czerlinsky T , White T W , Sasson S , Fisher S (1982) Simulated public speaking as a model of clinical anxiety. Psychopharmacology 77: 7–10

12.

McNair D M , Lorr M , Droppleman L F (1988) Manual for the profile of mood states. Educational and industrial testing service, San Diego, CA

13.

Mesulam M M (1985) Attention, confusional states and neglect. In Mesulam M M (ed.) Principles of behavioral neurology. Davis Company, Philadelphia, PA

14.

Miller H , Anderson I M , Deakin J F W (1995) Acute tryptophan depletion increases panic anxiety in panic disorder patients. J Psychopharmacol 9 (Suppl 3): A18-A18

15.

Milner B (1971) Interhemispheric differences in the localization of psychological processes in man. Br Med Bull 27: 272–277

16.

Neumeister A , Praschak-Rieder N , Hesselmann B , Vitouch O , Rauh M , Barocka A , Tauscher J , Kasper S (1998a) Effects of tryptophan depletion in drug-free depressed patients who responded to total sleep deprivation. Arch Gen Psychiatry 55: 167–172

17.

Neumeister A , Praschak-Rieder N , Hesselmann B , Vitouch O , Rauh M , Barocka A , Kasper S (1998b) Effects of tryptophan depletion in fully remitted patients with seasonal affective disorder during summer. Psychol Med 28: 257–264

18.

Nishizawa S , Benkelfat C , Young S N , Leyton M , Mzengeza S , de Montigny C , Blier P , Diksic M (1995) Differences between males and females in rates of serotonin synthesis in human brain. Proc Natl Acad Sci USA 94: 5308–5313

19.

Oldman A D , Walsh A E S , Salkovskis P , Laver D A , Cowen P J (1994) Effect of acute tryptophan depletion on mood and appetite in healthy male volunteers. J Psychopharmacol 8: 8–13

20.

Park S B , Coull J T , McShane R H , Young A H , Sahakian B J , Robbins T W , Cowen P J (1994) Tryptophan depletion in normal volunteers produces selective impairments in learning and memory. Neuropharmacology 33: 575–588

21.

Reilly J G , McTavish S F B , Young A H (1997) Rapid depletion of plasma tryptophan: a review of studies and experimental methodology. J Psychopharmacol 11: 381–392

22.

Riedel W J , Klaassen T , Deutz N E , van Someren A , van Praag H M (1999) Tryptophan depletion in normal volunteers produces selective impairment in memory consolidation. Psychopharmacology 141: 362–369

23.

Smith K , Fairburn C , Cowen P (1997) Relapse of depression after rapid depletion of tryptophan. Lancet 349: 915–919

24.

Wechsler D (1981) WAIS-R manual. Psychological Corporation, New York

25.

Young S N , Smith S E , Pihl R O , Ervin F R (1985) Tryptophan depletion causes a rapid lowering of mood in normal males. Psychopharmacology 87: 173–177