title: Cerebellar grey-matter deficits, cannabis use and first-episode schizophrenia in adolescents and young adults.
abstract: Epidemiological data link adolescent cannabis use to psychosis and schizophrenia, but its contribution to schizophrenia neuropathology remains controversial. First-episode schizophrenia (FES) patients show regional cerebral grey- and white-matter changes as well as a distinct pattern of regional grey-matter loss in the vermis of the cerebellum. The cerebellum possesses a high density of cannabinoid type 1 receptors involved in the neuronal diversification of the developing brain. Cannabis abuse may interfere with this process during adolescent brain maturation leading to 'schizophrenia-like' cerebellar pathology. Magnetic resonance imaging and cortical pattern matching techniques were used to investigate cerebellar grey and white matter in FES patients with and without a history of cannabis use and non-psychiatric cannabis users. In the latter group we found lifetime dose-dependent regional reduction of grey matter in the right cerebellar lobules and a tendency for more profound grey-matter reduction in lobule III with younger age at onset of cannabis use. The overall regional grey-matter differences in cannabis users were within the normal variability of grey-matter distribution. By contrast, FES subjects had lower total cerebellar grey-matter:total cerebellar volume ratio and marked grey-matter loss in the vermis, pedunculi, flocculi and lobules compared to pair-wise matched healthy control subjects. This pattern and degree of grey-matter loss did not differ from age-matched FES subjects with comorbid cannabis use. Our findings indicate small dose-dependent effects of juvenile cannabis use on cerebellar neuropathology but no evidence of an additional effect of cannabis use on FES cerebellar grey-matter pathology.
authors.affiliation: Schizophrenia Research Institute, Sydney, Australia.
authors.forename: Martin
authors.initials: M
authors.lastname: Cohen
authors.affiliation: Schizophrenia Research Institute, Sydney, Australia.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Rasser
authors.affiliation: Priority Centre for Brain & Mental Health Research, The University of Newcastle, Australia.
authors.forename: Greg
authors.initials: G
authors.lastname: Peck
authors.affiliation: Schizophrenia Research Institute, Sydney, Australia.
authors.forename: Vaughan J
authors.initials: VJ
authors.lastname: Carr
authors.affiliation: School of Psychiatry, University of New South Wales, Sydney, Australia.
authors.forename: Philip B
authors.initials: PB
authors.lastname: Ward
authors.affiliation: Laboratory of Neuro Imaging, University of California Los Angeles, CA, USA.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Thompson
authors.affiliation: Department of Psychology, University of York, UK.
authors.forename: Patrick
authors.initials: P
authors.lastname: Johnston
authors.affiliation: Schizophrenia Research Institute, Sydney, Australia.
authors.forename: Amanda
authors.initials: A
authors.lastname: Baker
authors.affiliation: Schizophrenia Research Institute, Sydney, Australia.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Schall
mesh_terms: D000367:Age Factors; D002188:Cannabis / Q000009:adverse effects; D002531:Cerebellum / Q000187:drug effects / Q000473:pathology*; D015897:Comorbidity; D004305:Dose-Response Relationship, Drug; D005260:Female; D066128:Gray Matter / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D002189:Marijuana Abuse / Q000453:epidemiology* / Q000473:pathology*; D009929:Organ Size; D012559:Schizophrenia / Q000453:epidemiology* / Q000473:pathology*; D066127:White Matter / Q000187:drug effects / Q000473:pathology; D055815:Young Adult