Mohini Ranganathan1, Jose Cortes-Briones2, Rajiv Radhakrishnan2, Halle Thurnauer2, Beata Planeta3, Patrick Skosnik2, Hong Gao4, David Labaree4, Alexander Neumeister5, Brian Pittman3, Toral Surti6, Yiyun Huang4, Richard E Carson4, Deepak Cyril D'Souza2. 1. Schizophrenia and Neuropharmacology Research Group, Veterans Affairs Connecticut Healthcare System, West Haven; Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven; Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut. Electronic address: mohini.ranganathan@yale.edu. 2. Schizophrenia and Neuropharmacology Research Group, Veterans Affairs Connecticut Healthcare System, West Haven; Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven; Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut. 3. Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven; Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; Positron Emission Tomography Center, Yale University School of Medicine, New Haven, Connecticut. 4. Positron Emission Tomography Center, Yale University School of Medicine, New Haven, Connecticut. 5. Molecular Imaging Program for Mood and Anxiety Disorders, New York University Langone Medical Center, New York, New York. 6. Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.
Abstract
BACKGROUND: Several lines of evidence suggest the presence of abnormalities in the endocannabinoid (eCB) system in schizophrenia (SCZ). However, there are limited in vivo measures of the eCB system in SCZ. METHODS: Twenty five male SCZ subjects (SCZs) (18 antipsychotic treated and 7 antipsychotic free) were compared with 18 age-matched male healthy control subjects (HCs). Subjects underwent one positron emission tomography scan each with the cannabinoid receptor-1 (CB1R) selective radiotracer [(11)C]OMAR on the high resolution research tomography scanner. Regional volume of distribution (VT) values were determined using kinetic modeling of positron emission tomography data as a measure of CB1R availability. Group differences in mean composite [(11)C]OMAR VT values were compared between SCZs and HCs. Exploratory comparisons of CB1R availability within 15 brain regions were also conducted. All analyses were covaried for age and body mass index. RESULTS: SCZs showed significantly (p = .02) lower composite [(11)C]OMAR VT relative to HCs (~12% difference, effect size d = .73). [(11)C]OMAR VT was significantly (all ps < .05) lower in SCZs in the amygdala, caudate, posterior cingulate cortex, hippocampus, hypothalamus, and insula. Composite [11]OMAR VT was HCs > antipsychotic treated SZCs > antipsychotic free SZCs. Furthermore, composite [(11)C]OMAR VT was greater in HCs than SCZ smokers (n = 11) and SCZ nonsmokers (n = 14). CONCLUSIONS: CB1R availability is lower in male SCZ subjects compared with HCs. Furthermore, antipsychotics and tobacco use may increase CB1R availability in this population. The findings of the study provide further evidence supporting the hypothesis that alterations in the eCB system might contribute to the pathophysiology of SCZ. Published by Elsevier Inc.
BACKGROUND: Several lines of evidence suggest the presence of abnormalities in the endocannabinoid (eCB) system in schizophrenia (SCZ). However, there are limited in vivo measures of the eCB system in SCZ. METHODS: Twenty five male SCZ subjects (SCZs) (18 antipsychotic treated and 7 antipsychotic free) were compared with 18 age-matched male healthy control subjects (HCs). Subjects underwent one positron emission tomography scan each with the cannabinoid receptor-1 (CB1R) selective radiotracer [(11)C]OMAR on the high resolution research tomography scanner. Regional volume of distribution (VT) values were determined using kinetic modeling of positron emission tomography data as a measure of CB1R availability. Group differences in mean composite [(11)C]OMAR VT values were compared between SCZs and HCs. Exploratory comparisons of CB1R availability within 15 brain regions were also conducted. All analyses were covaried for age and body mass index. RESULTS:SCZs showed significantly (p = .02) lower composite [(11)C]OMAR VT relative to HCs (~12% difference, effect size d = .73). [(11)C]OMAR VT was significantly (all ps < .05) lower in SCZs in the amygdala, caudate, posterior cingulate cortex, hippocampus, hypothalamus, and insula. Composite [11]OMAR VT was HCs > antipsychotic treated SZCs > antipsychotic free SZCs. Furthermore, composite [(11)C]OMAR VT was greater in HCs than SCZ smokers (n = 11) and SCZ nonsmokers (n = 14). CONCLUSIONS:CB1R availability is lower in male SCZ subjects compared with HCs. Furthermore, antipsychotics and tobacco use may increase CB1R availability in this population. The findings of the study provide further evidence supporting the hypothesis that alterations in the eCB system might contribute to the pathophysiology of SCZ. Published by Elsevier Inc.
Authors: Andrew G Horti; Hong Fan; Hiroto Kuwabara; John Hilton; Hayden T Ravert; Daniel P Holt; Mohab Alexander; Anil Kumar; Arman Rahmim; Ursula Scheffel; Dean F Wong; Robert F Dannals Journal: J Nucl Med Date: 2006-10 Impact factor: 10.057
Authors: Deepak Cyril D'Souza; Walid Michel Abi-Saab; Steven Madonick; Kimberlee Forselius-Bielen; Anne Doersch; Gabriel Braley; Ralitza Gueorguieva; Thomas B Cooper; John Harrison Krystal Journal: Biol Psychiatry Date: 2005-03-15 Impact factor: 13.382
Authors: F Markus Leweke; Andrea Giuffrida; Dagmar Koethe; Daniela Schreiber; Brit M Nolden; Laura Kranaster; Miriam A Neatby; Miriam Schneider; Christoph W Gerth; Martin Hellmich; Joachim Klosterkötter; Daniele Piomelli Journal: Schizophr Res Date: 2007-06-13 Impact factor: 4.939
Authors: A Neumeister; M D Normandin; R H Pietrzak; D Piomelli; M Q Zheng; A Gujarro-Anton; M N Potenza; C R Bailey; S F Lin; S Najafzadeh; J Ropchan; S Henry; S Corsi-Travali; R E Carson; Y Huang Journal: Mol Psychiatry Date: 2013-05-14 Impact factor: 15.992
Authors: Nicola De Marchi; Luciano De Petrocellis; Pierangelo Orlando; Fabiana Daniele; Filomena Fezza; Vincenzo Di Marzo Journal: Lipids Health Dis Date: 2003-08-19 Impact factor: 3.876
Authors: Mason M Silveira; Jonathon C Arnold; Steven R Laviolette; Cecilia J Hillard; Marta Celorrio; María S Aymerich; Wendy K Adams Journal: Neurosci Biobehav Rev Date: 2016-09-14 Impact factor: 8.989
Authors: Jussi Hirvonen; Paolo Zanotti-Fregonara; David A Gorelick; Chul Hyoung Lyoo; Denise Rallis-Frutos; Cheryl Morse; Sami S Zoghbi; Victor W Pike; Nora D Volkow; Marilyn A Huestis; Robert B Innis Journal: Biol Psychiatry Date: 2018-07-21 Impact factor: 13.382
Authors: Jeremy J Watts; Maya R Jacobson; Nittha Lalang; Isabelle Boileau; Rachel F Tyndale; Michael Kiang; Ruth A Ross; Sylvain Houle; Alan A Wilson; Pablo Rusjan; Romina Mizrahi Journal: Biol Psychiatry Date: 2020-03-12 Impact factor: 13.382
Authors: Lu Hou; Jian Rong; Ahmed Haider; Daisuke Ogasawara; Cassis Varlow; Michael A Schafroth; Linjing Mu; Jiefeng Gan; Hao Xu; Christopher J Fowler; Ming-Rong Zhang; Neil Vasdev; Simon Ametamey; Benjamin F Cravatt; Lu Wang; Steven H Liang Journal: J Med Chem Date: 2020-12-30 Impact factor: 7.446
Authors: Sagnik Bhattacharyya; Robin Wilson; Elizabeth Appiah-Kusi; Aisling O'Neill; Michael Brammer; Jesus Perez; Robin Murray; Paul Allen; Matthijs G Bossong; Philip McGuire Journal: JAMA Psychiatry Date: 2018-11-01 Impact factor: 21.596
Authors: Matthew E Sloan; Caroline W Grant; Joshua L Gowin; Vijay A Ramchandani; Bernard Le Foll Journal: Acta Pharmacol Sin Date: 2018-08-30 Impact factor: 6.150