Testing associations between cannabis use and subcortical volumes in two large population-based samples

Nathan A Gillespie; Michael C Neale; Timothy C Bates; Lisa T Eyler; Christine Fennema-Notestine; Jasmin Vassileva; Michael J Lyons; Elizabeth C Prom-Wormley; Katie L McMahon; Paul M Thompson; Greig de Zubicaray; Ian B Hickie; John J McGrath; Lachlan T Strike; Miguel E Rentería; Matthew S Panizzon; Nicholas G Martin; Carol E Franz; William S Kremen; Margaret J Wright

doi:10.1111/add.14252

Testing associations between cannabis use and subcortical volumes in two large population-based samples

Addiction. 2018 Apr 24:10.1111/add.14252. doi: 10.1111/add.14252. Online ahead of print.

Authors

Nathan A Gillespie^{1

2}, Michael C Neale¹, Timothy C Bates³, Lisa T Eyler^{4

5}, Christine Fennema-Notestine⁵, Jasmin Vassileva⁶, Michael J Lyons⁷, Elizabeth C Prom-Wormley⁸, Katie L McMahon⁹, Paul M Thompson⁹, Greig de Zubicaray^{10

11}, Ian B Hickie¹², John J McGrath^{13

14}, Lachlan T Strike^{2

9

10}, Miguel E Rentería², Matthew S Panizzon⁵, Nicholas G Martin², Carol E Franz⁵, William S Kremen^{5

14}, Margaret J Wright^{2

9}

Affiliations

¹ Virginia Institute for Psychiatric and Behavior Genetics, Virginia Commonwealth University, VA, USA.
² QIMR Berghofer Medical Research Institute, QLD, Australia.
³ Department of Psychology, University of Edinburgh, EH8 9JZ, UK.
⁴ Desert-Pacific Mental Illness Research, Education and Clinical Center, VA San Diego Healthcare System, CA, USA.
⁵ Department of Psychiatry, University of California San Diego, CA, USA.
⁶ Institute for Drug and Alcohol Studies, Virginia Commonwealth University, VA, USA.
⁷ Department of Psychological and Brain Sciences, Boston University, Boston, MA, USA.
⁸ Department of Family Medicine and Population Health, Virginia Commonwealth University, VA, USA.
⁹ Centre for Advanced Imaging, The University of Queensland, QLD, Australia.
¹⁰ School of Psychology, The University of Queensland, QLD, Australia.
¹¹ Faculty of Health and Institute of Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.
¹² Brain and Mind Research Institute, University of Sydney, NSW, Australia.
¹³ Queensland Brain Institute, The University of Queensland, QLD, Australia.
¹⁴ VA San Diego Center of Excellence for Stress and Mental Health, CA, USA.

Abstract

Background and aims: Disentangling the putative impact of cannabis on brain morphology from other comorbid substance use is critical. After controlling for the effects of nicotine, alcohol and multi-substance use, this study aimed to determine whether frequent cannabis use is associated with significantly smaller subcortical grey matter volumes.

Design: Exploratory analyses using mixed linear models, one per region of interest (ROI), were performed whereby individual differences in volume (outcome) at seven subcortical ROIs were regressed onto cannabis and comorbid substance use (predictors).

Setting: Two large population-based twin samples from the United States and Australia.

Participants: A total of 622 young Australian adults [66% female; μ_age = 25.9, standard deviation SD) = 3.6] and 474 middle-aged US males (μ_age = 56.1_{SD = 2.6} ) of predominately Anglo-Saxon ancestry with complete substance use and imaging data. Subjects with a history of stroke or traumatic brain injury were excluded.

Measurements: Magnetic resonance imaging (MRI) and volumetric segmentation methods were used to estimate volume in seven subcortical ROIs: thalamus, caudate nucleus, putamen, pallidum, hippocampus, amygdala and nucleus accumbens. Substance use measurements included maximum nicotine and alcohol use, total life-time multi-substance use, maximum cannabis use in the young adults and regular cannabis use in the middle-aged males.

Findings: After correcting for multiple testing (P = 0.007), cannabis use was unrelated to any subcortical ROI. However, maximum nicotine use was associated with significantly smaller thalamus volumes in middle-aged males.

Conclusions: In exploratory analyses based on young adult and middle-aged samples, normal variation in cannabis use is unrelated statistically to individual differences in brain morphology as measured by subcortical volume.

Keywords: Brain volume; cannabis use; grey matter; imaging; multi-substance use; subcortical.

Abstract

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