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

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

A. J. Willem Van der Does

Department of Psychology, Leiden University and Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands

P. M. Judith Haffmans

Psychomedical Center Parnassia, The Hague, The Netherlands

Wim J. Riedel

Department of Psychiatry, University of Cambridge, Cambridge, UK, Faculty of Psychology, Maastricht University, Maastricht, The Netherlands and GlaxoSmithKline, Translational Medicine and Technology, Cambridge, UK

Durk Fekkes

Departments of Psychiatry and Neuroscience, Erasmus University Medical Center, Rotterdam, The Netherlands

Marc J. B. Blom

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 afterdepletion. 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 theprocessing 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 ofemotional 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.

Key Words: catecholamine • cognition • depletion • depression • serotonin • tryptophan

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