title: Orbitofrontal and caudate volumes in cannabis users: a multi-site mega-analysis comparing dependent versus non-dependent users.
abstract: BACKGROUND
  Cannabis (CB) use and dependence are associated with regionally specific alterations to brain circuitry and substantial psychosocial impairment.
  
  
  OBJECTIVE
  The objective of this study was to investigate the association between CB use and dependence, and the volumes of brain regions critically involved in goal-directed learning and behaviour-the orbitofrontal cortex (OFC) and caudate.
  
  
  METHODS
  In the largest multi-site structural imaging study of CB users vs healthy controls (HC), 140 CB users and 121 HC were recruited from four research sites. Group differences in OFC and caudate volumes were investigated between HC and CB users and between 70 dependent (CB-dep) and 50 non-dependent (CB-nondep) users. The relationship between quantity of CB use and age of onset of use and caudate and OFC volumes was explored.
  
  
  RESULTS
  CB users (consisting of CB-dep and CB-nondep) did not significantly differ from HC in OFC or caudate volume. CB-dep compared to CB-nondep users exhibited significantly smaller volume in the medial and the lateral OFC. Lateral OFC volume was particularly smaller in CB-dep females, and reduced volume in the CB-dep group was associated with higher monthly cannabis dosage.
  
  
  CONCLUSIONS
  Smaller medial OFC volume may be driven by CB dependence-related mechanisms, while smaller lateral OFC volume may be due to ongoing exposure to cannabinoid compounds. The results highlight a distinction between cannabis use and dependence and warrant examination of gender-specific effects in studies of CB dependence.
authors.affiliation: Brain and Mental Health Laboratory, Monash Institute of Cognitive and Clinical Neurosciences, School of Psychological Sciences, Monash University, Melbourne, Australia.
authors.forename: Yann
authors.initials: Y
authors.lastname: Chye
authors.affiliation: School of Psychology and Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, Australia.
authors.forename: Nadia
authors.initials: N
authors.lastname: Solowij
authors.affiliation: Brain and Mental Health Laboratory, Monash Institute of Cognitive and Clinical Neurosciences, School of Psychological Sciences, Monash University, Melbourne, Australia.
authors.forename: Chao
authors.initials: C
authors.lastname: Suo
authors.affiliation: Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands.|Department of Psychiatry and Psychology, Hospital Clinic, IDIBAPS, CIBERSAM and Institute of Neuroscience, University of Barcelona, Barcelona, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Batalla
authors.affiliation: Department of Developmental Psychology, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Janna
authors.initials: J
authors.lastname: Cousijn
authors.affiliation: Department of Psychiatry, Amsterdam Institute for Addiction Research, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.|Arkin Mental Health Care, Amsterdam, The Netherlands.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Goudriaan
authors.affiliation: Department of Psychiatry and Psychology, Hospital Clinic, IDIBAPS, CIBERSAM and Institute of Neuroscience, University of Barcelona, Barcelona, Spain.
authors.forename: Rocio
authors.initials: R
authors.lastname: Martin-Santos
authors.affiliation: Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Melbourne, Australia.
authors.forename: Sarah
authors.initials: S
authors.lastname: Whittle
authors.affiliation: Brain and Mental Health Laboratory, Monash Institute of Cognitive and Clinical Neurosciences, School of Psychological Sciences, Monash University, Melbourne, Australia. vlor@liv.ac.uk.|Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Melbourne, Australia. vlor@liv.ac.uk.|School of Psychological Sciences, Institute of Psychology, Health and Society, The University of Liverpool, Liverpool, UK. vlor@liv.ac.uk.
authors.forename: Valentina
authors.initials: V
authors.lastname: Lorenzetti
authors.affiliation: Brain and Mental Health Laboratory, Monash Institute of Cognitive and Clinical Neurosciences, School of Psychological Sciences, Monash University, Melbourne, Australia. murat.yucel@monash.edu.
authors.forename: Murat
authors.initials: M
authors.lastname: Yücel
mesh_terms: D001921:Brain / Q000502:physiology*; D001931:Brain Mapping / Q000379:methods; D002755:Choice Behavior; D005625:Frontal Lobe / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D002189:Marijuana Abuse; D008385:Marijuana Smoking / Q000378:metabolism; D017397:Prefrontal Cortex / Q000502:physiology*; D019966:Substance-Related Disorders
keywords: Brain structure; Cannabis; Caudate; Dependence; Gender; MRI; Orbitofrontal cortex