title: Reduced Brain Cannabinoid Receptor Availability in Schizophrenia.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: 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.
authors.forename: Mohini
authors.initials: M
authors.lastname: Ranganathan
authors.affiliation: 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.
authors.forename: Jose
authors.initials: J
authors.lastname: Cortes-Briones
authors.affiliation: 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.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Radhakrishnan
authors.affiliation: 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.
authors.forename: Halle
authors.initials: H
authors.lastname: Thurnauer
authors.affiliation: 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.
authors.forename: Beata
authors.initials: B
authors.lastname: Planeta
authors.affiliation: 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.
authors.forename: Patrick
authors.initials: P
authors.lastname: Skosnik
authors.affiliation: Positron Emission Tomography Center, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Hong
authors.initials: H
authors.lastname: Gao
authors.affiliation: Positron Emission Tomography Center, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: David
authors.initials: D
authors.lastname: Labaree
authors.affiliation: Molecular Imaging Program for Mood and Anxiety Disorders, New York University Langone Medical Center, New York, New York.
authors.forename: Alexander
authors.initials: A
authors.lastname: Neumeister
authors.affiliation: 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.
authors.forename: Brian
authors.initials: B
authors.lastname: Pittman
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Toral
authors.initials: T
authors.lastname: Surti
authors.affiliation: Positron Emission Tomography Center, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Positron Emission Tomography Center, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Carson
authors.affiliation: 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.
authors.forename: Deepak Cyril
authors.initials: DC
authors.lastname: D'Souza
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects / Q000378:metabolism*; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism*; D012907:Smoking; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D019275:Radiopharmaceuticals; D043884:Receptor, Cannabinoid, CB1
keywords: Antipsychotics; CB(1)R; Cannabinoid; OMAR; Schizophrenia; Smoking