title: Orbitofrontal volumes in early adolescence predict initiation of cannabis use: a 4-year longitudinal and prospective study.
abstract: BACKGROUND
  There is growing evidence that long-term, heavy cannabis use is associated with alterations in regional brain volumes. Although these changes are frequently attributed to the neurotoxic effects of cannabis, it is possible that some abnormalities might predate use and represent markers of vulnerability. To date, no studies have examined whether structural brain abnormalities are present before the onset of cannabis use. This study aims to determine whether adolescents who have initiated cannabis use early (i.e., before age 17 years) show premorbid structural abnormalities in the amygdala, hippocampus, orbitofrontal cortex, and anterior cingulate cortex.
  
  
  METHODS
  Participants (n = 121) were recruited from primary schools in Melbourne, Australia, as part of a larger study examining adolescent emotional development. Participants underwent structural magnetic resonance imaging at age 12 years and were assessed for cannabis use 4 years later, at age 16 years. At the follow-up assessment, 28 participants had commenced using cannabis (16 female subjects [57%]), and 93 had not (43 female subjects [46%]).
  
  
  RESULTS
  Smaller orbitofrontal cortex volumes at age 12 years predicted initiation of cannabis use by age 16 years. The volumes of other regions (amygdala, hippocampus, and anterior cingulate cortex) did not predict later cannabis use.
  
  
  CONCLUSIONS
  These findings suggest that structural abnormalities in the orbitofrontal cortex might contribute to risk for cannabis exposure. Although the results have important implications for understanding neurobiological predictors of cannabis use, further research is needed to understand their relationship with heavier patterns of use in adulthood as well as later abuse of other substances.
authors: Orygen Youth Health Research Centre, Centre for Youth Mental Health, University of Melbourne, Parkville, Australia.
authors: Ali
authors: A
authors: Cheetham
authors: Nicholas B
authors: NB
authors: Allen
authors: Sarah
authors: S
authors: Whittle
authors: Julian G
authors: JG
authors: Simmons
authors: Murat
authors: M
authors: Yücel
authors: Dan I
authors: DI
authors: Lubman
mesh_terms: D000293:Adolescent; D002648:Child; D005260:Female; D005625:Frontal Lobe / Q000473:pathology*; D006801:Humans; D008032:Limbic System / Q000473:pathology*; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008385:Marijuana Smoking / Q000473:pathology*; D009929:Organ Size; D011446:Prospective Studies