The effects of acute tryptophan depletion on brain activation during cognition and emotional processing in healthy volunteers.

Acute tryptophan depletion (ATD), a method to temporarily lower central serotonin levels, has been used to study the functioning of the serotonergic system. Relatively recent studies that examined the effects of ATD on brain activation associated with cognitive and emotional processing in healthy volunteers are reviewed. An overview of the findings in healthy volunteers is important for the interpretation of the effect of ATD on brain activation in patients with an affective disorder, such as major depression. These studies show that during response control and negative feedback processing ATD modulates the BOLD response in the inferior/orbitofrontal cortex, the anterior cingulate cortex and the dorsomedial prefrontal cortex. During emotional processing, it is consistently found that ATD modulates the BOLD response in the amygdala. These brain regions also show abnormal activation in depressed patients. However, at the moment it remains unclear if the changes induced by ATD are related to decreased basal serotonin (5-HT) release or the result of other biochemical changes that are mediated by ATD. Future studies should implement methodological improvements, explore the possibilities of new promising imaging techniques and expand investigations into the effects of ATD on basal 5-HT release and other biochemical mechanisms that might be modulated by ATD.

[1]  I. Winkler,et al.  Memory-based or afferent processes in mismatch negativity (MMN): a review of the evidence. , 2005, Psychophysiology.

[2]  Mark Slifstein,et al.  Effects of reduced endogenous 5‐HT on the in vivo binding of the serotonin transporter radioligand 11C‐DASB in healthy humans , 2005, Synapse.

[3]  Cynthia H. Y. Fu,et al.  Tryptophan depletion reduces right inferior prefrontal activation during response inhibition in fast, event-related fMRI , 2005, Psychopharmacology.

[4]  R. Ilmoniemi,et al.  Auditory selective attention modulated by tryptophan depletion in humans , 2003, Neuroscience Letters.

[5]  Gavin P. Reynolds,et al.  Acute and chronic tryptophan depletion differentially regulate central 5-HT1A and 5-HT2A receptor binding in the rat , 2007, Psychopharmacology.

[6]  N. Zahniser,et al.  Chronic and acute regulation of Na+/Cl- -dependent neurotransmitter transporters: drugs, substrates, presynaptic receptors, and signaling systems. , 2001, Pharmacology & therapeutics.

[7]  Thomas Dierks,et al.  Intensity dependence of auditory evoked potentials (AEPs) as biological marker for cerebral serotonin levels: effects of tryptophan depletion in healthy subjects , 1999, Psychopharmacology.

[8]  C. Benkelfat,et al.  Behavioral disinhibition induced by tryptophan depletion in nonalcoholic young men with multigenerational family histories of paternal alcoholism. , 1999, The American journal of psychiatry.

[9]  Sylvia M. L. Cox,et al.  Tryptophan Depletion Disrupts the Motivational Guidance of Goal-Directed Behavior as a Function of Trait Impulsivity , 2005, Neuropsychopharmacology.

[10]  T. Robbins,et al.  Stop signal response inhibition is not modulated by tryptophan depletion or the serotonin transporter polymorphism in healthy volunteers: implications for the 5-HT theory of impulsivity , 2005, Psychopharmacology.

[11]  J. Ahveninen,et al.  Serotonergic modulation of mismatch negativity , 2005, Psychiatry Research: Neuroimaging.

[12]  S. Fromm,et al.  The Effect of Acute Tryptophan Depletion on the Neural Correlates of Emotional Processing in Healthy Volunteers , 2008, Neuropsychopharmacology.

[13]  Philip K. McGuire,et al.  Modulation of neural response to happy and sad faces by acute tryptophan depletion , 2007, Psychopharmacology.

[14]  Marcus E Raichle,et al.  Glucose metabolism in the amygdala in depression: Relationship to diagnostic subtype and plasma cortisol levels , 2002, Pharmacology Biochemistry and Behavior.

[15]  T. Robbins,et al.  Reconciling the Role of Serotonin in Behavioral Inhibition and Aversion: Acute Tryptophan Depletion Abolishes Punishment-Induced Inhibition in Humans , 2009, The Journal of Neuroscience.

[16]  Peggy Dean,et al.  Mood Response to Acute Tryptophan Depletion in Healthy Volunteers: Sex Differences and Temporal Stability , 1996, Neuropsychopharmacology.

[17]  W. Riedel,et al.  Effects of acute tryptophan depletion on memory, attention and executive functions: A systematic review , 2009, Neuroscience & Biobehavioral Reviews.

[18]  Joseph E LeDoux,et al.  Contributions of the Amygdala to Emotion Processing: From Animal Models to Human Behavior , 2005, Neuron.

[19]  J. Ahveninen,et al.  Acute trytophan depletion decreases intensity dependence of auditory evoked magnetic N1/P2 dipole source activity , 2002, Psychopharmacology.

[20]  M. Trulson.  Dietary tryptophan does not alter the function of brain serotonin neurons. , 1985, Life sciences.

[21]  T. Robbins,et al.  Tryptophan depletion impairs stimulus-reward learning while methylphenidate disrupts attentional control in healthy young adults: implications for the monoaminergic basis of impulsive behaviour , 1999, Psychopharmacology.

[22]  D. Faller,et al.  NEUTRAL AMINO ACIDS IN THE BRAIN: CHANGES IN RESPONSE TO FOOD INGESTION 1 , 1978, Journal of neurochemistry.

[23]  T. L. Davis,et al.  Calibrated functional MRI: mapping the dynamics of oxidative metabolism. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[24]  Peter S Talbot,et al.  Anterior Cingulate and Subgenual Prefrontal Blood Flow Changes Following Tryptophan Depletion in Healthy Males , 2006, Neuropsychopharmacology.

[25]  W J Riedel,et al.  Tryptophan depletion impairs memory consolidation but improves focussed attention in healthy young volunteers , 2000, Journal of psychopharmacology.

[26]  A Honig,et al.  Cognition following acute tryptophan depletion: difference between first-degree relatives of bipolar disorder patients and matched healthy control volunteers , 2002, Psychological Medicine.

[27]  T. Robbins,et al.  Individual differences in threat sensitivity predict serotonergic modulation of amygdala response to fearful faces , 2005, Psychopharmacology.

[28]  M Diksic,et al.  Differences between males and females in rates of serotonin synthesis in human brain. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[29]  D. Kumaran,et al.  A Genetically Mediated Bias in Decision Making Driven by Failure of Amygdala Control , 2009, The Journal of Neuroscience.

[30]  W. Riedel,et al.  Monoamine depletion in psychiatric and healthy populations: review , 2003, Molecular Psychiatry.

[31]  Pradeep J Nathan,et al.  Acute Serotonin and Dopamine Depletion Improves Attentional Control: Findings from the Stroop Task , 2007, Neuropsychopharmacology.

[32]  Jyrki Ahveninen,et al.  Serotonin Modulates Early Cortical Auditory Processing in Healthy Subjects. Evidence from MEG with Acute Tryptophan Depletion , 2002, Neuropsychopharmacology.

[33]  Acute tryptophan depletion does not change somatosensory evoked magnetic fields , 2003, Psychopharmacology.

[34]  R. Schreiber,et al.  The Selective 5-HT6 Receptor Antagonist Ro4368554 Restores Memory Performance in Cholinergic and Serotonergic Models of Memory Deficiency in the Rat , 2005, Neuropsychopharmacology.

[35]  Arjan Blokland,et al.  Anxiogenic and depressive-like effects, but no cognitive deficits, after repeated moderate tryptophan depletion in the rat , 2002, Journal of psychopharmacology.

[36]  R. Bell,et al.  Effect of acute tryptophan depletion on noradrenaline and dopamine in the rat brain , 2009, Journal of psychopharmacology.

[37]  Gregory McCarthy,et al.  The effect of acute tryptophan depletion on emotional distraction and subsequent memory. , 2009, Social cognitive and affective neuroscience.

[38]  G. Kovacs,et al.  Aldosterone blocks the response to corticosterone in the raphe-hippocampal serotonin system , 1983, Brain Research.

[39]  P. Soubrié.  Reconciling the role of central serotonin neurons in human and animal behavior , 1986, Behavioral and Brain Sciences.

[40]  W. Riedel,et al.  The effects of high-dose and low-dose tryptophan depletion on mood and cognitive functions of remitted depressed patients , 2005, Journal of psychopharmacology.

[41]  D Hommer,et al.  Effects of Acute Tryptophan Depletion on Plasma and Cerebrospinal Fluid Tryptophan and 5‐Hydroxyindoleacetic Acid in Normal Volunteers , 1999, Journal of neurochemistry.

[42]  R. Wurtman,et al.  Precursor control of neurotransmitter synthesis. , 1980, Pharmacological reviews.

[43]  P F Liddle,et al.  Effects of rapid tryptophan depletion on brain 5-HT2 receptors: a PET study , 2001, British Journal of Psychiatry.

[44]  C Dockery,et al.  The effect of tryptophan depletion on brain activation measured by functional magnetic resonance imaging during the Stroop test in healthy subjects. , 2005, Physiological research.

[45]  M. Mintun,et al.  Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment: an fMRI study , 2001, Biological Psychiatry.

[46]  Philip K. McGuire,et al.  Effect of acute tryptophan depletion on pre-frontal engagement , 2006, Psychopharmacology.

[47]  P. Whitaker-Azmitia,et al.  Serotonin depletion during synaptogenesis leads to decreased synaptic density and learning deficits in the adult rat: a possible model of neurodevelopmental disorders with cognitive deficits , 1997, Brain Research.

[48]  T. Robbins,et al.  Serotonergic Modulation of Prefrontal Cortex during Negative Feedback in Probabilistic Reversal Learning , 2005, Neuropsychopharmacology.

[49]  C. Benkelfat,et al.  Tryptophan Depletion, Executive Functions, and Disinhibition in Aggressive, Adolescent Males , 1998, Neuropsychopharmacology.

[50]  M. Furey,et al.  Brain structural and functional abnormalities in mood disorders: implications for neurocircuitry models of depression , 2008, Brain Structure and Function.

[51]  Mariko Osaka,et al.  Cooperation of the anterior cingulate cortex and dorsolateral prefrontal cortex for attention shifting , 2004, NeuroImage.

[52]  Afonso C Silva,et al.  Measurement of cerebral perfusion territories using arterial spin labelling , 2007, NMR in biomedicine.

[53]  W. Riedel,et al.  Tryptophan, mood, and cognitive function , 2002, Brain, Behavior, and Immunity.

[54]  M. Fava,et al.  Predictors of Mood Response to Acute Tryptophan Depletion: A Reanalysis , 2002, Neuropsychopharmacology.

[55]  B. Westerink,et al.  Acute tryptophan and serotonin depletion using an optimized tryptophan-free protein–carbohydrate mixture in the adult rat , 2004, Neurochemistry International.

[56]  Jan Pruim,et al.  5‐HT1A receptor imaging in the human brain: Effect of tryptophan depletion and infusion on [18F]MPPF binding , 2002 .

[57]  John Suckling,et al.  Attenuation of the neural response to sad faces in major depression by antidepressant treatment: a prospective, event-related functional magnetic resonance imaging study. , 2004, Archives of general psychiatry.

[58]  M. Rugg,et al.  Effects of tryptophan depletion on brain potential correlates of episodic memory retrieval , 2002, Psychopharmacology.

[59]  T. Robbins.  Arousal systems and attentional processes , 1997, Biological Psychology.

[60]  A. Blokland,et al.  Acute tryptophan depletion in rats alters the relationship between cerebral blood flow and glucose metabolism independent of central serotonin , 2009, Neuroscience.

[61]  B. Costall,et al.  The effects of ondansetron, a 5-HT3 receptor antagonist, on cognition in rodents and primates , 1990, Pharmacology Biochemistry and Behavior.

[62]  M. W. Molen,et al.  Acute tryptophan depletion in healthy males attenuates phasic cardiac slowing but does not affect electro-cortical response to negative feedback , 2008, Psychopharmacology.

[63]  A. Young,et al.  Sex differences in the effect of acute tryptophan depletion on declarative episodic memory: A pooled analysis of nine studies , 2007, Neuroscience & Biobehavioral Reviews.

[64]  V. Knott,et al.  The effect of acute tryptophan depletion and fenfluramine on quantitative EEG and mood in healthy male subjects , 1999, Biological Psychiatry.

[65]  T. Robbins,et al.  Central serotonin depletion impairs both the acquisition and performance of a symmetrically reinforced go/no-go conditional visual discrimination , 1999, Behavioural Brain Research.

[66]  J. T. Coull,et al.  Tryptophan depletion in normal volunteers produces selective impairments in learning and memory , 1994, Neuropharmacology.

[67]  Peter Gallagher,et al.  Effects of acute tryptophan depletion on executive function in healthy male volunteers , 2003, BMC psychiatry.

[68]  R. Pihl,et al.  Biochemical aspects of tryptophan depletion in primates , 2004, Psychopharmacology.

[69]  C. Benkelfat,et al.  Mood-lowering effect of tryptophan depletion. Enhanced susceptibility in young men at genetic risk for major affective disorders. , 1994, Archives of general psychiatry.

[70]  P. Delgado,et al.  CSF neurochemicals during tryptophan depletion in individuals with remitted depression and healthy controls , 2010, European Neuropsychopharmacology.

[71]  W. Riedel,et al.  Tryptophan depletion in normal volunteers produces selective impairment in memory consolidation , 1999, Psychopharmacology.

[72]  P. Cowen,et al.  Tryptophan depletion decreases the recognition of fear in female volunteers , 2003, Psychopharmacology.

[73]  Rebecca Elliott,et al.  The Effect of Citalopram Pretreatment on Neuronal Responses to Neuropsychological Tasks in Normal Volunteers: An fMRI Study , 2005, Neuropsychopharmacology.

[74]  W. Riedel,et al.  Mood effects of 24-hour tryptophan depletion in healthy first-degree relatives of patients with affective disorders , 1999, Biological Psychiatry.

[75]  Walter H. Backes,et al.  Acute tryptophan depletion reduces activation in the right hippocampus during encoding in an episodic memory task , 2006, NeuroImage.

[76]  Jelle Jolles,et al.  Acute tryptophan depletion improves performance and modulates the BOLD response during a Stroop task in healthy females , 2006, NeuroImage.

[77]  Sylvain Houle,et al.  Effects of Tryptophan Depletion on the Serotonin Transporter in Healthy Humans , 2005, Biological Psychiatry.

[78]  A. V. D. Does,et al.  The effects of tryptophan depletion on mood and psychiatric symptoms. , 2001 .

[79]  D Friedman,et al.  Event‐related potential (ERP) studies of memory encoding and retrieval: A selective review , 2000, Microscopy research and technique.

[80]  T. Robbins,et al.  The neuropsychopharmacology of fronto-executive function: monoaminergic modulation. , 2009, Annual review of neuroscience.

[81]  Stefan Pollmann,et al.  Anterior prefrontal cortex contributions to attention control. , 2004, Experimental psychology.

[82]  S. Stahl,et al.  Book Review: Essential Psychopharmacology: Neuroscientific Basis and Practical Applications, 2nd Edition , 1996 .

[83]  C. Carter,et al.  Tryptophan Depletion Alters the Decision-Making of Healthy Volunteers through Altered Processing of Reward Cues , 2003, Neuropsychopharmacology.

[84]  T. Robbins,et al.  Chemical neuromodulation of frontal-executive functions in humans and other animals , 2000, Experimental Brain Research.

[85]  Katya Rubia,et al.  5-HT, prefrontal function and aging: fMRI of inhibition and acute tryptophan depletion , 2009, Neurobiology of Aging.

[86]  W. Riedel,et al.  Stress, cortisol and memory as markers of serotonergic vulnerability , 2002, Acta Neuropsychiatrica.

[87]  A. Blokland,et al.  Lack of evidence for reduced prefrontal cortical serotonin and dopamine efflux after acute tryptophan depletion , 2007, Psychopharmacology.

[88]  G. Biggio,et al.  Rapid depletion of serum tryptophan, brain tryptophan, serotonin and 5-hydroxyindoleacetic acid by a tryptophan-free diet. , 1974, Life sciences.

[89]  C. Andrade,et al.  Stahl's Essential Psychopharmacology: Neuroscientific Basis and Practical Applications , 2010, Mens Sana Monographs.

[90]  C. Nemeroff,et al.  Neurochemical alterations of serotonergic neuronal systems in depression. , 1992, The Journal of clinical psychiatry.

[91]  E. Evers,et al.  Effects of Acute Tryptophan Depletion on Mood and Facial Emotion Perception Related Brain Activation and Performance in Healthy Women with and without a Family History of Depression , 2007, Neuropsychopharmacology.

[92]  A. Young,et al.  Acute depletion of plasma tryptophan does not alter electrophysiological variables in healthy males , 2000, Psychopharmacology.

[93]  Marcus R. Munafò,et al.  Serotonin Transporter (5-HTTLPR) Genotype and Amygdala Activation: A Meta-Analysis , 2008, Biological Psychiatry.

[94]  C. Carver,et al.  Behavioral inhibition, behavioral activation, and affective responses to impending reward and punishment: The BIS/BAS Scales , 1994 .

[95]  A. Blokland,et al.  Stress-mediated decreases in brain-derived neurotrophic factor as potential confounding factor for acute tryptophan depletion-induced neurochemical effects , 2009, European Neuropsychopharmacology.

[96]  S. Cooper,et al.  Acute tryptophan depletion does not alter central or plasma brain-derived neurotrophic factor in the rat , 2008, European Neuropsychopharmacology.

[97]  A. Young,et al.  Rapid depletion of plasma tryptophan: a review of studies and experimental methodology , 1997, Journal of psychopharmacology.

[98]  T. Robbins,et al.  Serotonin Transporter Polymorphism Mediates Vulnerability to Loss of Incentive Motivation Following Acute Tryptophan Depletion , 2006, Neuropsychopharmacology.

[99]  W. Riedel,et al.  Tryptophan modulation and cognition. , 2003, Advances in experimental medicine and biology.

[100]  G. Telegdy,et al.  Decreased serotonin turnover in the dorsal hippocampus of rat brain shortly after adrenalectomy: selective normalization after corticosterone substitution , 1982, Brain Research.

[101]  André Beauducel,et al.  Is auditory evoked potential augmenting/reducing affected by acute tryptophan depletion? , 2002, Biological Psychology.

[102]  Barry J. Everitt,et al.  Central 5-HT depletion enhances impulsive responding without affecting the accuracy of attentional performance: interactions with dopaminergic mechanisms , 1997, Psychopharmacology.

[103]  Yasuyuki Sakai,et al.  Cortical trapping of α-[11C]methyl-l-tryptophan, an index of serotonin synthesis, is lower in females than males , 2006, NeuroImage.

[104]  R. Blakely,et al.  Regulated phosphorylation and trafficking of antidepressant-sensitive serotonin transporter proteins , 1998, Biological Psychiatry.

[105]  M. Sarter,et al.  Modulators in concert for cognition: Modulator interactions in the prefrontal cortex , 2007, Progress in Neurobiology.

[106]  W H Oldendorf,et al.  Amino acid assignment to one of three blood-brain barrier amino acid carriers. , 1976, The American journal of physiology.

[107]  T. Robbins,et al.  The effects of tryptophan depletion on cognitive and affective processing in healthy volunteers , 2002, Psychopharmacology.

[108]  Iiro P. Jääskeläinen,et al.  Tryptophan Depletion Effects on EEG and MEG Responses Suggest Serotonergic Modulation of Auditory Involuntary Attention in Humans , 2002, NeuroImage.

[109]  Husseini Manji,et al.  Effects of tryptophan depletion on serum levels of brain-derived neurotrophic factor in unmedicated patients with remitted depression and healthy subjects. , 2005, The American journal of psychiatry.

[110]  L. D. van de Kar,et al.  Fluoxetine-induced changes in body weight and 5-HT1A receptor-mediated hormone secretion in rats on a tryptophan-deficient diet. , 2004, American journal of physiology. Regulatory, integrative and comparative physiology.

[111]  G. Iannetti,et al.  BOLD functional MRI in disease and pharmacological studies: room for improvement? , 2007, Magnetic resonance imaging.

[112]  S. Stahl.  Comprar Stahl's Essential Psychopharmacology. Neuroscientific Basis and Practical Applications | Stephen M. Stahl | 9780521857024 | Cambridge University Press , 2008 .

[113]  D. Perrett,et al.  Differential effects of tryptophan depletion on emotion processing according to face direction. , 2007, Social cognitive and affective neuroscience.

[114]  R. Pihl,et al.  Tryptophan depletion causes a rapid lowering of mood in normal males , 2004, Psychopharmacology.