Cannabis use and resting state functional connectivity in adolescent bipolar disorder

Alysha A Sultan; Megan A Hird; Mikaela K Dimick; Bradley J MacIntosh; Benjamin I Goldstein

doi:10.1503/jpn.200228

Cannabis use and resting state functional connectivity in adolescent bipolar disorder

J Psychiatry Neurosci. 2021 Sep;46(5):E559-E567. doi: 10.1503/jpn.200228.

Authors

Alysha A Sultan¹, Megan A Hird¹, Mikaela K Dimick¹, Bradley J MacIntosh¹, Benjamin I Goldstein²

Affiliations

¹ From the Centre for Youth Bipolar Disorder, Centre for Addiction and Mental Health, (Sultan, Hird, Dimick, Goldstein); the Department of Pharmacology and Toxicology, University of Toronto, (Sultan, Dimick, Goldstein); the Faculty of Medicine, University of Toronto, (Sultan, Hird, Dimick, Goldstein); the Department of Psychiatry, University of Toronto, (Goldstein); the Department of Medical Biophysics, University of Toronto, (MacIntosh); and the Hurvitz Brain Sciences, Sunnybrook Health Sciences Centre, (MacIntosh, Goldstein) Toronto, Ont. Canada.
² From the Centre for Youth Bipolar Disorder, Centre for Addiction and Mental Health, (Sultan, Hird, Dimick, Goldstein); the Department of Pharmacology and Toxicology, University of Toronto, (Sultan, Dimick, Goldstein); the Faculty of Medicine, University of Toronto, (Sultan, Hird, Dimick, Goldstein); the Department of Psychiatry, University of Toronto, (Goldstein); the Department of Medical Biophysics, University of Toronto, (MacIntosh); and the Hurvitz Brain Sciences, Sunnybrook Health Sciences Centre, (MacIntosh, Goldstein) Toronto, Ont. Canada. benjamin.goldstein@camh.ca.

Abstract

Background: Adolescents with bipolar disorder have high rates of cannabis use, and cannabis use is associated with increased symptom severity and treatment resistance in bipolar disorder. Studies have identified anomalous resting-state functional connectivity among reward networks in bipolar disorder and cannabis use independently, but have yet to examine their convergence.

Methods: Participants included 134 adolescents, aged 13 to 20 years: 40 with bipolar disorder and lifetime cannabis use, 31 with bipolar disorder and no history of cannabis use, and 63 healthy controls without lifetime cannabis use. We used a seed-to-voxel analysis to assess the restingstate functional connectivity of the amygdala, the nucleus accumbens and the orbitofrontal cortex, regions implicated in bipolar disorder and cannabis use. We used a generalized linear model to explore bivariate correlations for each seed, controlling for age and sex.

Results: We found 3 significant clusters. Resting-state functional connectivity between the left nucleus accumbens seed and the left superior parietal lobe was negative in adolescents with bipolar disorder and no history of cannabis use, and positive in healthy controls. Resting-state functional connectivity between the right orbitofrontal cortex seed and the right lateral occipital cortex was positive in adolescents with bipolar disorder and lifetime cannabis use, and negative in healthy controls and adolescents with bipolar disorder and no history of cannabis use. Resting-state functional connectivity between the right orbitofrontal cortex seed and right occipital pole was positive in adolescents with bipolar disorder and lifetime cannabis use, and negative in adolescents with bipolar disorder and no history of cannabis use.

Limitations: The study did not include a cannabis-using control group.

Conclusion: This study provides preliminary evidence of cannabis-related differences in functional reward circuits in adolescents with bipolar disorder. Further studies are necessary to evaluate whether the present findings reflect consequences of or predisposition to cannabis use.

MeSH terms

Adolescent
Amygdala / physiopathology
Bipolar Disorder / physiopathology*
Cannabis*
Female
Humans
Male
Marijuana Use*
Neural Pathways* / physiopathology
Nucleus Accumbens / physiopathology
Prefrontal Cortex / physiopathology
Rest*
Reward*