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Orbitofrontal Volumes in Early Adolescence Predict Initiation of Cannabis Use: A 4-Year Longitudinal and Prospective Study

  • Ali Cheetham
    Affiliations
    Orygen Youth Health Research Centre, Centre for Youth Mental Health, University of Melbourne, Parkville, Australia
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  • Nicholas B. Allen
    Affiliations
    Orygen Youth Health Research Centre, Centre for Youth Mental Health, University of Melbourne, Parkville, Australia

    Department of Psychological Sciences, University of Melbourne, Parkville, Australia
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  • Sarah Whittle
    Affiliations
    Orygen Youth Health Research Centre, Centre for Youth Mental Health, University of Melbourne, Parkville, Australia

    Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne and Melbourne Health, St Albans, Australia
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  • Julian G. Simmons
    Affiliations
    Orygen Youth Health Research Centre, Centre for Youth Mental Health, University of Melbourne, Parkville, Australia
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  • Murat Yücel
    Affiliations
    Orygen Youth Health Research Centre, Centre for Youth Mental Health, University of Melbourne, Parkville, Australia

    Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne and Melbourne Health, St Albans, Australia
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  • Dan I. Lubman
    Correspondence
    Address correspondence to Dan Lubman, MB, Ch.B., Ph.D., Eastern Health and Monash University, Turning Point Alcohol and Drug Centre, 54-62 Gertrude Street, Fitzroy, Victoria 3065 Australia
    Affiliations
    Turning Point Alcohol and Drug Centre, Eastern Health and Monash University, Fitzroy, Victoria, Australia
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Published:December 02, 2011DOI:https://doi.org/10.1016/j.biopsych.2011.10.029

      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.

      Key Words

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      Linked Article

      • Orbitofrontal Cortex and Neuromaturation: A Gateway to Risk?
        Biological PsychiatryVol. 71Issue 8
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          Adolescence is a period of intense vulnerability to drug use initiation, and adolescents may be more susceptible than adults to becoming drug-dependent (1). Cannabis use initiation during adolescence has emerged as a significant concern because early initiation of cannabis use has been associated with increased risk for using a range of other drugs of abuse (2). A central challenge to understanding substance abuse behavior is determining why some individuals initiate drug use and become dependent and others do not (1).
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