Linh C Dang1, Gregory R Samanez-Larkin2, Jaime J Castrellon3, Scott F Perkins3, Ronald L Cowan4, David H Zald5. 1. Department of Psychology, Vanderbilt University, 219 Wilson Hall, 111 21st Avenue South, Nashville, TN 37203, USA. Electronic address: linh.dang@vanderbilt.edu. 2. Department of Psychology, Yale University, 2 Hillhouse Avenue, New Haven, CT 06520, USA. 3. Department of Psychology, Vanderbilt University, 219 Wilson Hall, 111 21st Avenue South, Nashville, TN 37203, USA. 4. Department of Psychiatry, Vanderbilt University School of Medicine, 1601 23rd Ave South, Nashville, TN 37212, USA; Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, 1211 Medical Center Drive, Nashville, TN 37232, USA. 5. Department of Psychology, Vanderbilt University, 219 Wilson Hall, 111 21st Avenue South, Nashville, TN 37203, USA; Department of Psychiatry, Vanderbilt University School of Medicine, 1601 23rd Ave South, Nashville, TN 37212, USA.
Abstract
OBJECTIVE: The dopamine D2/3 receptor subtypes (DRD2/3) are the most widely studied neurotransmitter biomarker in research on obesity, but results to date have been inconsistent, have typically involved small samples, and have rarely accounted for subjects' ages despite the large impact of age on DRD2/3 levels. We aimed to clarify the relation between DRD2/3 availability and BMI by examining this association in a large sample of subjects with BMI spanning the continuum from underweight to extremely obese. SUBJECTS: 130 healthy subjects between 18 and 81years old underwent PET with [18F]fallypride, a high affinity DRD2/3 ligand. RESULTS: As expected, DRD2/3 availability declined with age. Critically, age significantly interacted with DRD2/3 availability in predicting BMI in the midbrain and striatal regions (caudate, putamen, and ventral striatum). Among subjects under 30years old, BMI was not associated with DRD2/3 availability. By contrast, among subjects over 30years old, BMI was positively associated with DRD2/3 availability in the midbrain, putamen, and ventral striatum. CONCLUSION: The present results are incompatible with the prominent dopaminergic hypofunction hypothesis that proposes that a reduction in DRD2/3 availability is associated with increased BMI, and highlights the importance of age in assessing correlates of DRD2/3 function.
OBJECTIVE: The dopamine D2/3 receptor subtypes (DRD2/3) are the most widely studied neurotransmitter biomarker in research on obesity, but results to date have been inconsistent, have typically involved small samples, and have rarely accounted for subjects' ages despite the large impact of age on DRD2/3 levels. We aimed to clarify the relation between DRD2/3 availability and BMI by examining this association in a large sample of subjects with BMI spanning the continuum from underweight to extremely obese. SUBJECTS: 130 healthy subjects between 18 and 81years old underwent PET with [18F]fallypride, a high affinity DRD2/3 ligand. RESULTS: As expected, DRD2/3 availability declined with age. Critically, age significantly interacted with DRD2/3 availability in predicting BMI in the midbrain and striatal regions (caudate, putamen, and ventral striatum). Among subjects under 30years old, BMI was not associated with DRD2/3 availability. By contrast, among subjects over 30years old, BMI was positively associated with DRD2/3 availability in the midbrain, putamen, and ventral striatum. CONCLUSION: The present results are incompatible with the prominent dopaminergic hypofunction hypothesis that proposes that a reduction in DRD2/3 availability is associated with increased BMI, and highlights the importance of age in assessing correlates of DRD2/3 function.
Authors: O Mawlawi; D Martinez; M Slifstein; A Broft; R Chatterjee; D R Hwang; Y Huang; N Simpson; K Ngo; R Van Heertum; M Laruelle Journal: J Cereb Blood Flow Metab Date: 2001-09 Impact factor: 6.200
Authors: E P Noble; R E Noble; T Ritchie; K Syndulko; M C Bohlman; L A Noble; Y Zhang; R S Sparkes; D K Grandy Journal: Int J Eat Disord Date: 1994-04 Impact factor: 4.861
Authors: Vanessa L Cropley; Robert B Innis; Pradeep J Nathan; Amira K Brown; Janet L Sangare; Alicja Lerner; Yong Hoon Ryu; Kelly E Sprague; Victor W Pike; Masahiro Fujita Journal: Synapse Date: 2008-06 Impact factor: 2.562
Authors: Lauri T Haltia; Juha O Rinne; Harri Merisaari; Ralph P Maguire; Eriika Savontaus; Semi Helin; Kjell Någren; Valtteri Kaasinen Journal: Synapse Date: 2007-09 Impact factor: 2.562
Authors: Sarah A Eisenstein; Danuta M Gredysa; Jo Ann Antenor-Dorsey; Leonard Green; Ana Maria Arbeláez; Jonathan M Koller; Kevin J Black; Joel S Perlmutter; Stephen M Moerlein; Tamara Hershey Journal: PLoS One Date: 2015-07-20 Impact factor: 3.240
Authors: Kendra L Seaman; Christopher T Smith; Eric J Juarez; Linh C Dang; Jaime J Castrellon; Leah L Burgess; M Danica San Juan; Paul M Kundzicz; Ronald L Cowan; David H Zald; Gregory R Samanez-Larkin Journal: Hum Brain Mapp Date: 2019-04-01 Impact factor: 5.038
Authors: Paul A M Smeets; Alain Dagher; Todd A Hare; Stephanie Kullmann; Laura N van der Laan; Russell A Poldrack; Hubert Preissl; Dana Small; Eric Stice; Maria G Veldhuizen Journal: Am J Clin Nutr Date: 2019-03-01 Impact factor: 7.045
Authors: Fernando Caravaggio; Jun Ku Chung; Eric Plitman; Isabelle Boileau; Philip Gerretsen; Julia Kim; Yusuke Iwata; Raihaan Patel; M Mallar Chakravarty; Gary Remington; Ariel Graff-Guerrero Journal: Hum Brain Mapp Date: 2017-07-28 Impact factor: 5.038
Authors: Linh C Dang; Gregory R Samanez-Larkin; Christopher T Smith; Jaime J Castrellon; Scott F Perkins; Ronald L Cowan; Daniel O Claassen; David H Zald Journal: Physiol Behav Date: 2017-12-09
Authors: Corinde E Wiers; Elizabeth A Cabrera; Dardo Tomasi; Christopher T Wong; Şükrü B Demiral; Sung Won Kim; Gene-Jack Wang; Nora D Volkow Journal: Neuropsychopharmacology Date: 2017-06-23 Impact factor: 7.853
Authors: Marie A Labouesse; Andrea M Sartori; Oliver Weinmann; Eleanor H Simpson; Christoph Kellendonk; Ulrike Weber-Stadlbauer Journal: Proc Natl Acad Sci U S A Date: 2018-09-25 Impact factor: 11.205
Authors: Martin Lövdén; Nina Karalija; Micael Andersson; Anders Wåhlin; Jan Axelsson; Ylva Köhncke; Lars S Jonasson; Anna Rieckman; Goran Papenberg; Douglas D Garrett; Marc Guitart-Masip; Alireza Salami; Katrine Riklund; Lars Bäckman; Lars Nyberg; Ulman Lindenberger Journal: Cereb Cortex Date: 2018-11-01 Impact factor: 5.357
Authors: A Gupta; E A Mayer; K Hamadani; R Bhatt; C Fling; M Alaverdyan; C Torgerson; C Ashe-McNalley; J D Van Horn; B Naliboff; K Tillisch; C P Sanmiguel; J S Labus Journal: Int J Obes (Lond) Date: 2017-03-31 Impact factor: 5.095
Authors: Adam J Stark; Christopher T Smith; Kalen J Petersen; Paula Trujillo; Nelleke C van Wouwe; Manus J Donahue; Robert M Kessler; Ariel Y Deutch; David H Zald; Daniel O Claassen Journal: Neuroimage Clin Date: 2018-02-10 Impact factor: 4.881