Lower dopamine tone in the striatum is associated with higher body mass index

Existing literature suggests that striatal dopamine (DA) tone may be altered in individuals with higher body mass index (BMI), but evidence accrued so far only offers an incomplete view of their relationship. Here, we characterized striatal DA tone using more comprehensive measures within a larger sample than previously reported. In addition, we explored if there was a relationship between striatal DA tone and disinhibited eating. 60 healthy participants underwent a 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine (18F-DOPA) positron emission tomography (PET) scan. Disinhibited eating was measured with the Three-Factor Eating Questionnaire on a baseline visit. Individual whole-brain PET parameter estimates, namely 18F-DOPA influx rate constant (kocc i.e. DA synthesis capacity), 18F-DA washout rate (kloss) and effective distribution volume ratio (EDVR= kocc/ kloss), were derived with a reversible-tracer graphical analysis approach. We then computed parameter estimates for three regions-of-interests (ROIs), namely the ventral striatum, putamen and caudate. Overweight/mildly obese individuals had lowered EDVR than normal weight individuals in all three ROIs. The most prominent of these associations, driven by lowered kocc (r = -.28, p = .035) and heightened kloss (r = .48, p < .001), was found in the ventral striatum (r = -.46, p < .001). Disinhibition was greater in higher-BMI individuals (r = .31, p = .015), but was unrelated to PET measures and did not explain the relationship between PET measures and BMI. In sum, our findings resonate with the notion that overweight/mildly obese individuals have lower striatal DA tone and suggest new avenues for investigating their underlying mechanisms.

[1]  S. Killcross,et al.  Amphetamine Exposure Enhances Habit Formation , 2006, The Journal of Neuroscience.

[2]  C Nahmias,et al.  Cerebral Metabolism of 6–[18F]Fluoro‐l‐3,4‐Dihydroxyphenylalanine in the Primate , 1987, Journal of neurochemistry.

[3]  J. Lammertyn,et al.  How is reward sensitivity related to bodyweight in children? , 2012, Appetite.

[4]  H. Reichmann,et al.  Putaminal dopamine turnover in de novo Parkinson disease predicts later motor complications , 2016, Neurology.

[5]  P. Vernier,et al.  The Evolution of Dopamine Systems in Chordates , 2011, Front. Neuroanat..

[6]  H. Reichmann,et al.  Comparison of dopamine turnover, dopamine influx constant and activity ratio of striatum and occipital brain with 18F-dopa brain PET in normal controls and patients with Parkinson’s disease , 2011, European Journal of Nuclear Medicine and Molecular Imaging.

[7]  T. Robbins,et al.  Reliance on habits at the expense of goal-directed control following dopamine precursor depletion , 2011, Psychopharmacology.

[8]  Ronald L. Cowan,et al.  Associations between dopamine D2 receptor availability and BMI depend on age , 2016, NeuroImage.

[9]  W. Jagust,et al.  Overeating Behavior and Striatal Dopamine with 6-[18F]-Fluoro-L-m-Tyrosine PET , 2010, Journal of obesity.

[10]  M. K. Das,et al.  Fluorinated benzamide neuroleptics--III. Development of (S)-N-[(1-allyl-2-pyrrolidinyl)methyl]-5-(3-[18F]fluoropropyl)-2, 3-dimethoxybenzamide as an improved dopamine D-2 receptor tracer. , 1995, Nuclear medicine and biology.

[11]  B. Balleine Neural bases of food-seeking: Affect, arousal and reward in corticostriatolimbic circuits , 2005, Physiology & Behavior.

[12]  G. Koutsis,et al.  Elevated CSF serotonin and dopamine metabolite levels in overweight subjects , 2013, Obesity.

[13]  Philip K. McGuire,et al.  The test–retest reliability of 18F-DOPA PET in assessing striatal and extrastriatal presynaptic dopaminergic function , 2010, NeuroImage.

[14]  V Sossi,et al.  A Reversible Tracer Analysis Approach to the Study of Effective Dopamine Turnover , 2001, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[15]  H. Yin,et al.  The role of the basal ganglia in habit formation , 2006, Nature Reviews Neuroscience.

[16]  Annette Horstmann It wasn't me; it was my brain – Obesity-associated characteristics of brain circuits governing decision-making , 2017, Physiology & Behavior.

[17]  Ivan E. de Araújo,et al.  Weighing the evidence: Variance in brain responses to milkshake receipt is predictive of eating behavior , 2016, NeuroImage.

[18]  MJ Bond,et al.  The measurement of dietary restraint, disinhibition and hunger: an examination of the factor structure of the Three Factor Eating Questionnaire (TFEQ) , 2001, International Journal of Obesity.

[19]  Amanda E. Babbs,et al.  Basolateral Amygdala Response to Food Cues in the Absence of Hunger Is Associated with Weight Gain Susceptibility , 2015, The Journal of Neuroscience.

[20]  M. Luijendijk,et al.  Does activation of midbrain dopamine neurons promote or reduce feeding? , 2017, International Journal of Obesity.

[21]  Nils B. Kroemer,et al.  Fuel not fun: Reinterpreting attenuated brain responses to reward in obesity , 2016, Physiology & Behavior.

[22]  J. Blundell,et al.  Disinhibition: its effects on appetite and weight regulation , 2007, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[23]  Jean Logan,et al.  Brain dopamine and obesity , 2001, The Lancet.

[24]  N. Tzourio-Mazoyer,et al.  Automated Anatomical Labeling of Activations in SPM Using a Macroscopic Anatomical Parcellation of the MNI MRI Single-Subject Brain , 2002, NeuroImage.

[25]  Annette Horstmann,et al.  Argument for a non‐linear relationship between severity of human obesity and dopaminergic tone , 2015, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[26]  Rebecca G. Boswell,et al.  Food cue reactivity and craving predict eating and weight gain: a meta‐analytic review , 2016, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[27]  Edgar Erdfelder,et al.  G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences , 2007, Behavior research methods.

[28]  H. Kimura,et al.  Human positron emission tomographic [18F]Fluorodopa studies correlate with dopamine cell counts and levels , 1993, Annals of neurology.

[29]  V. Sossi,et al.  Effect of Dopamine Loss and the Metabolite 3-O-Methyl-[18F]Fluoro-dopa on the Relation between the 18F-Fluorodopa Tissue Input Uptake Rate Constant Kocc and the [18F]Fluorodopa Plasma Input Uptake Rate Constant Ki , 2003, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[30]  Alan A. Wilson,et al.  Reduced Insulin Sensitivity Is Related to Less Endogenous Dopamine at D2/3 Receptors in the Ventral Striatum of Healthy Nonobese Humans , 2015, The international journal of neuropsychopharmacology.

[31]  A. Stunkard,et al.  The three-factor eating questionnaire to measure dietary restraint, disinhibition and hunger. , 1985, Journal of psychosomatic research.

[32]  Alexander W. Johnson Eating beyond metabolic need: how environmental cues influence feeding behavior , 2013, Trends in Neurosciences.

[33]  D. Goldman,et al.  A functional polymorphism in the MAOA gene promoter (MAOA-LPR) predicts central dopamine function and body mass index , 2006, Molecular Psychiatry.

[34]  Deanna L. Wallace,et al.  Dorsal Striatal Dopamine, Food Preference and Health Perception in Humans , 2014, PloS one.

[35]  E. Stice,et al.  Neural vulnerability factors that increase risk for future weight gain. , 2016, Psychological bulletin.

[36]  J. Neumann,et al.  Slave to habit? Obesity is associated with decreased behavioural sensitivity to reward devaluation , 2014, Appetite.

[37]  R. Norgren,et al.  Repeated access to sucrose augments dopamine turnover in the nucleus accumbens , 2002, Neuroreport.

[38]  A. Grace,et al.  Afferent modulation of dopamine neuron firing differentially regulates tonic and phasic dopamine transmission , 2003, Nature Neuroscience.

[39]  Alan A. Wilson,et al.  Ventral Striatum Binding of a Dopamine D2/3 Receptor Agonist But Not Antagonist Predicts Normal Body Mass Index , 2015, Biological Psychiatry.

[40]  C. Davis,et al.  Sensitivity to reward: implications for overeating and overweight , 2004, Appetite.

[41]  W. K. Simmons,et al.  Striatal dopamine D2-like receptor correlation patterns with human obesity and opportunistic eating behavior , 2014, Molecular Psychiatry.

[42]  Paul J. Laurienti,et al.  An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets , 2003, NeuroImage.

[43]  J C Mazziotta,et al.  The effects of carbidopa administration on 6-[18F]fluoro-L-dopa kinetics in positron emission tomography. , 1992, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[44]  B. Eppinger,et al.  L-DOPA Reduces Model-Free Control of Behavior by Attenuating the Transfer of Value to Action , 2016, bioRxiv.

[45]  Thomas E. Nichols,et al.  Handbook of Functional MRI Data Analysis: Index , 2011 .

[46]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[47]  Sunoo Park,et al.  It wasn't me! Repudiability and Unclaimability of Ring Signatures , 2019, IACR Cryptol. ePrint Arch..

[48]  Annette Horstmann,et al.  Age- and gender-specific norms for the German version of the Three-Factor Eating-Questionnaire (TFEQ) , 2015, Appetite.

[49]  V. Sossi,et al.  Increase in Dopamine Turnover Occurs Early in Parkinson's Disease: Evidence from a New Modeling Approach to PET 18F-Fluorodopa Data , 2002, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[50]  G. Stuber,et al.  Modulation of cue-induced firing of ventral tegmental area dopamine neurons by leptin and ghrelin , 2015, International Journal of Obesity.

[51]  N. Volkow,et al.  Relationship of Dopamine Type 2 Receptor Binding Potential With Fasting Neuroendocrine Hormones and Insulin Sensitivity in Human Obesity , 2012, Diabetes Care.

[52]  Kyle S. Burger,et al.  Greater striatopallidal adaptive coding during cue–reward learning and food reward habituation predict future weight gain , 2014, NeuroImage.

[53]  H. Berthoud Brain, appetite and obesity. , 2008, Physiology & behavior.

[54]  Thomas E. Nichols,et al.  Controlling the familywise error rate in functional neuroimaging: a comparative review , 2003, Statistical methods in medical research.

[55]  D. Zald,et al.  Changes in dopamine release and dopamine D2/3 receptor levels with the development of mild obesity , 2014, Synapse.

[56]  Fumitoshi Kodaka,et al.  Relation between Presynaptic and Postsynaptic Dopaminergic Functions Measured by Positron Emission Tomography: Implication of Dopaminergic Tone , 2011, The Journal of Neuroscience.

[57]  Mark Jenkinson,et al.  Imaging dopamine receptors in humans with [11C]-(+)-PHNO: Dissection of D3 signal and anatomy , 2011, NeuroImage.

[58]  J E Holden,et al.  Evaluation of Dopaminergic Presynaptic Integrity: 6-[18F]Fluoro-L-Dopa Versus 6-[18F]Fluoro-L-m-Tyrosine , 1999, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[59]  A. Grace,et al.  The Yin and Yang of dopamine release: a new perspective , 2007, Neuropharmacology.

[60]  P. Kenny,et al.  Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats , 2010, Nature Neuroscience.

[61]  J. J. Cone,et al.  Ghrelin regulates phasic dopamine and nucleus accumbens signaling evoked by food‐predictive stimuli , 2015, Journal of neurochemistry.

[62]  C. Patlak,et al.  Graphical Evaluation of Blood-to-Brain Transfer Constants from Multiple-Time Uptake Data. Generalizations , 1985, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[63]  F. Paccaud,et al.  Consequences of smoking for body weight, body fat distribution, and insulin resistance. , 2008, The American journal of clinical nutrition.

[64]  Paul Cumming,et al.  PET Studies of Cerebral Levodopa Metabolism: A Review of Clinical Findings and Modeling Approaches , 2009, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[65]  Karl J. Friston,et al.  Unified segmentation , 2005, NeuroImage.

[66]  Alexxai V. Kravitz,et al.  Do Dopaminergic Impairments Underlie Physical Inactivity in People with Obesity? , 2016, Front. Hum. Neurosci..

[67]  M. Laruelle Imaging Synaptic Neurotransmission with in Vivo Binding Competition Techniques: A Critical Review , 2000, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[68]  F. Mottaghy,et al.  Effects of Smoking Cessation on Presynaptic Dopamine Function of Addicted Male Smokers , 2016, Biological Psychiatry.

[69]  R. Dolan,et al.  Ventral striatal prediction error signaling is associated with dopamine synthesis capacity and fluid intelligence , 2013, Human brain mapping.

[70]  Jon F. Davis,et al.  Exposure to elevated levels of dietary fat attenuates psychostimulant reward and mesolimbic dopamine turnover in the rat. , 2008, Behavioral neuroscience.

[71]  A. Grace Phasic versus tonic dopamine release and the modulation of dopamine system responsivity: A hypothesis for the etiology of schizophrenia , 1991, Neuroscience.

[72]  J. Salamone,et al.  Nucleus Accumbens Dopamine and the Regulation of Effort in Food-Seeking Behavior: Implications for Studies of Natural Motivation, Psychiatry, and Drug Abuse , 2003, Journal of Pharmacology and Experimental Therapeutics.

[73]  A. Grace,et al.  The Catechol-O-Methyltransferase Polymorphism: Relations to the Tonic–Phasic Dopamine Hypothesis and Neuropsychiatric Phenotypes , 2004, Neuropsychopharmacology.

[74]  R. Seeley,et al.  The integrative role of CNS fuel-sensing mechanisms in energy balance and glucose regulation. , 2008, Annual review of physiology.

[75]  A. Dagher,et al.  Dopamine-based reward circuitry responsivity, genetics, and overeating. , 2011, Current topics in behavioral neurosciences.

[76]  Alan C. Evans,et al.  Dopa decarboxylase activity of the living human brain. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[77]  D. Sulzer,et al.  How Addictive Drugs Disrupt Presynaptic Dopamine Neurotransmission , 2011, Neuron.