Food can lift mood by affecting mood-regulating neurocircuits via a serotonergic mechanism

It is commonly assumed that food can affect mood. One prevalent notion is that food containing tryptophan increases serotonin levels in the brain and alters neural processing in mood-regulating neurocircuits. However, tryptophan competes with other long-neutral-amino-acids (LNAA) for transport across the blood-brain-barrier, a limitation that can be mitigated by increasing the tryptophan/LNAA ratio. We therefore tested in a double-blind, placebo-controlled crossover study (N=32) whether a drink with a favourable tryptophan/LNAA ratio improves mood and modulates specific brain processes as assessed by functional magnetic resonance imaging (fMRI). We show that one serving of this drink increases the tryptophan/LNAA ratio in blood plasma, lifts mood in healthy young women and alters task-specific and resting-state processing in brain regions implicated in mood regulation. Specifically, Test-drink consumption reduced neural responses of the dorsal caudate nucleus during reward anticipation, increased neural responses in the dorsal cingulate cortex during fear processing, and increased ventromedial prefrontal-lateral prefrontal connectivity under resting-state conditions. Our results suggest that increasing tryptophan/LNAA ratios can lift mood by affecting mood-regulating neurocircuits.

[1]  B. Abler,et al.  Modulation of Frontostriatal Interaction Aligns with Reduced Primary Reward Processing under Serotonergic Drugs , 2012, The Journal of Neuroscience.

[2]  T L Faber,et al.  Neural activity related to drug craving in cocaine addiction. , 2001, Archives of general psychiatry.

[3]  C. Spielberger,et al.  Manual for the State-Trait Anxiety Inventory , 1970 .

[4]  Jessica A. Grahn,et al.  The cognitive functions of the caudate nucleus , 2008, Progress in Neurobiology.

[5]  Yang Wang,et al.  Reciprocal effects of antidepressant treatment on activity and connectivity of the mood regulating circuit: an FMRI study. , 2007, The Journal of neuropsychiatry and clinical neurosciences.

[6]  Christian Büchel,et al.  Amygdala-prefrontal coupling depends on a genetic variation of the serotonin transporter , 2005, Nature Neuroscience.

[7]  Michael A. Andrykowski,et al.  Short Form of the Profile of Mood States (POMS-SF): Psychometric Information. , 1995 .

[8]  Brian Knutson,et al.  Anticipation of Increasing Monetary Reward Selectively Recruits Nucleus Accumbens , 2001, The Journal of Neuroscience.

[9]  D. Sakas,et al.  Connections of the basal ganglia with the limbic system: implications for neuromodulation therapies of anxiety and affective disorders. , 2007, Acta neurochirurgica. Supplement.

[10]  N. Kalin,et al.  Reduced capacity to sustain positive emotion in major depression reflects diminished maintenance of fronto-striatal brain activation , 2009, Proceedings of the National Academy of Sciences.

[11]  K. Ressler,et al.  Targeting abnormal neural circuits in mood and anxiety disorders: from the laboratory to the clinic , 2007, Nature Neuroscience.

[12]  P. Cowen,et al.  Diminished Neural Processing of Aversive and Rewarding Stimuli During Selective Serotonin Reuptake Inhibitor Treatment , 2010, Biological Psychiatry.

[13]  Ciara McCabe,et al.  Antidepressant medications reduce subcortical–cortical resting-state functional connectivity in healthy volunteers , 2011, NeuroImage.

[14]  Marc G Caron,et al.  Uptake and Release of Norepinephrine by Serotonergic Terminals in Norepinephrine Transporter Knock-Out Mice: Implications for the Action of Selective Serotonin Reuptake Inhibitors , 2004, The Journal of Neuroscience.

[15]  S. Haber,et al.  The Reward Circuit: Linking Primate Anatomy and Human Imaging , 2010, Neuropsychopharmacology.

[16]  R. Elliott,et al.  Playing it safe but losing anyway—Serotonergic signaling of negative outcomes in dorsomedial prefrontal cortex in the context of risk-aversion , 2013, European Neuropsychopharmacology.

[17]  Lorena Hsu,et al.  Prevalence and Incidence Studies of Anxiety Disorders: A Systematic Review of the Literature , 2004, Canadian journal of psychiatry. Revue canadienne de psychiatrie.

[18]  Jeffrey L. Birk,et al.  Reduced caudate and nucleus accumbens response to rewards in unmedicated individuals with major depressive disorder. , 2009, The American journal of psychiatry.

[19]  J. Gross,et al.  The cognitive control of emotion , 2005, Trends in Cognitive Sciences.

[20]  C. Markus Dietary Amino Acids and Brain Serotonin Function; Implications for Stress-Related Affective Changes , 2008, NeuroMolecular Medicine.

[21]  Eliza Congdon,et al.  Additive effects of serotonin transporter and tryptophan hydroxylase-2 gene variation on neural correlates of affective processing , 2008, Biological Psychology.

[22]  Francesco Fera,et al.  Dextroamphetamine Modulates the Response of the Human Amygdala , 2002, Neuropsychopharmacology.

[23]  S. Bishop,et al.  Neural Mechanisms Underlying Selective Attention to Threat , 2008, Annals of the New York Academy of Sciences.

[24]  Patrick M Fisher,et al.  Acute 5-HT Reuptake Blockade Potentiates Human Amygdala Reactivity , 2008, Neuropsychopharmacology.

[25]  C. Firk,et al.  Effect of different tryptophan sources on amino acids availability to the brain and mood in healthy volunteers , 2008, Psychopharmacology.

[26]  T. Robbins,et al.  Converging evidence for central 5-HT effects in acute tryptophan depletion , 2012, Molecular Psychiatry.

[27]  Rupert Lanzenberger,et al.  Correlations and anticorrelations in resting-state functional connectivity MRI: A quantitative comparison of preprocessing strategies , 2009, NeuroImage.

[28]  M. Fox,et al.  The global signal and observed anticorrelated resting state brain networks. , 2009, Journal of neurophysiology.

[29]  T. Prentice World Health Report , 2013 .

[30]  P. Cowen,et al.  Effects of pramipexole on the processing of rewarding and aversive taste stimuli , 2013, Psychopharmacology.

[31]  S. Shacham,et al.  A shortened version of the Profile of Mood States. , 1983, Journal of personality assessment.

[32]  Veena Kumari,et al.  Neuroticism and brain responses to anticipatory fear. , 2007, Behavioral neuroscience.

[33]  M. Hamer,et al.  The role of functional foods in the psychobiology of health and disease , 2005, Nutrition Research Reviews.

[34]  C. Harmer,et al.  Paradoxical effects of short-term antidepressant treatment in fMRI emotional processing models in volunteers with high neuroticism , 2013, Psychological Medicine.

[35]  S. Derbyshire,et al.  Exploring the pain “neuromatrix” , 2000, Current review of pain.

[36]  B. Vogt,et al.  Architecture and neurocytology of monkey cingulate gyrus , 2005, The Journal of comparative neurology.

[37]  N. Daw,et al.  Serotonin and Dopamine: Unifying Affective, Activational, and Decision Functions , 2011, Neuropsychopharmacology.

[38]  J. Price,et al.  Neurocircuitry of Mood Disorders , 2010, Neuropsychopharmacology.

[39]  Saori C. Tanaka,et al.  Serotonin Affects Association of Aversive Outcomes to Past Actions , 2009, The Journal of Neuroscience.

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

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

[42]  A. Meyer-Lindenberg,et al.  5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression , 2005, Nature Neuroscience.

[43]  Julian M Somers,et al.  Prevalence and Incidence Studies of Mood Disorders: A Systematic Review of the Literature , 2004, Canadian journal of psychiatry. Revue canadienne de psychiatrie.

[44]  F. Zitman,et al.  Tryptophan depletion affects the autonomic stress response in generalized social anxiety disorder , 2009, Psychoneuroendocrinology.

[45]  R. Davidson,et al.  The integration of negative affect, pain and cognitive control in the cingulate cortex , 2011, Nature Reviews Neuroscience.

[46]  Joseph E LeDoux,et al.  Neural Circuitry Underlying the Regulation of Conditioned Fear and Its Relation to Extinction , 2008, Neuron.

[47]  C. Saper,et al.  The Need to Feed Homeostatic and Hedonic Control of Eating , 2002, Neuron.

[48]  P. Cowen,et al.  Neural representation of reward in recovered depressed patients , 2009, Psychopharmacology.

[49]  Terry E. Robinson,et al.  Incentive-sensitization As The Basis Of Drug Craving , 1993 .

[50]  P. Cowen,et al.  A single dose of mirtazapine modulates neural responses to emotional faces in healthy people , 2010, Psychopharmacology.

[51]  Maurizio Corbetta,et al.  The human brain is intrinsically organized into dynamic, anticorrelated functional networks. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

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

[53]  C. Cepko,et al.  The External Granule Layer of the Developing Chick Cerebellum Generates Granule Cells and Cells of the Isthmus and Rostral Hindbrain , 2001, The Journal of Neuroscience.

[54]  Kevin Murphy,et al.  The impact of global signal regression on resting state correlations: Are anti-correlated networks introduced? , 2009, NeuroImage.