Dataset Information

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

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; ?age = 25.9, standard deviation SD) = 3.6] and 474 middle-aged US males (?age = 56.1SD = 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.

SUBMITTER: Gillespie NA

PROVIDER: S-EPMC6200645 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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

Gillespie Nathan A NA Neale Michael C MC Bates Timothy C TC Eyler Lisa T LT Fennema-Notestine Christine C Vassileva Jasmin J Lyons Michael J MJ Prom-Wormley Elizabeth C EC McMahon Katie L KL Thompson Paul M PM de Zubicaray Greig G Hickie Ian B IB McGrath John J JJ Strike Lachlan T LT Rentería Miguel E ME Panizzon Matthew S MS Martin Nicholas G NG Franz Carol E CE Kremen William S WS Wright Margaret J MJ

Addiction (Abingdon, England) 20180424

<h4>Background and aims</h4>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.<h4>Design</h4>Exploratory analyses using mixed linear models, one per region of interest (ROI), were performed whereby individual differences in ...[more]

PMID: 29691937

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Project description:ImportancePrior neuroimaging studies have suggested that alterations in brain structure may be a consequence of cannabis use. Siblings discordant for cannabis use offer an opportunity to use cross-sectional data to disentangle such causal hypotheses from shared effects of genetics and familial environment on brain structure and cannabis use.ObjectivesTo determine whether cannabis use is associated with differences in brain structure in a large sample of twins/siblings and to examine sibling pairs discordant for cannabis use to separate potential causal and predispositional factors linking lifetime cannabis exposure to volumetric alterations.Design, setting, and participantsCross-sectional diagnostic interview, behavioral, and neuroimaging data were collected from community sampling and established family registries from August 2012 to September 2014. This study included data from 483 participants (22-35 years old) enrolled in the ongoing Human Connectome Project, with 262 participants reporting cannabis exposure (ie, ever used cannabis in their lifetime).Main outcomes and measuresCannabis exposure was measured with the Semi-Structured Assessment for the Genetics of Alcoholism. Whole-brain, hippocampus, amygdala, ventral striatum, and orbitofrontal cortex volumes were related to lifetime cannabis use (ever used, age at onset, and frequency of use) using linear regressions. Genetic (ρg) and environmental (ρe) correlations between cannabis use and brain volumes were estimated. Linear mixed models were used to examine volume differences in sex-matched concordant unexposed (n = 71 pairs), exposed (n = 81 pairs), or exposure discordant (n = 89 pairs) sibling pairs.ResultsAmong 483 study participants, cannabis exposure was related to smaller left amygdala (approximately 2.3%; P = .007) and right ventral striatum (approximately 3.5%; P < .005) volumes. These volumetric differences were within the range of normal variation. The association between left amygdala volume and cannabis use was largely owing to shared genetic factors (ρg = -0.43; P = .004), while the origin of the association with right ventral striatum volumes was unclear. Importantly, brain volumes did not differ between sex-matched siblings discordant for use (fixed effect = -7.43; t = -0.93, P = .35). Both the exposed and unexposed siblings in pairs discordant for cannabis exposure showed reduced amygdala volumes relative to members of concordant unexposed pairs (fixed effect = 12.56; t = 2.97; P = .003).Conclusions and relevanceIn this study, differences in amygdala volume in cannabis users were attributable to common predispositional factors, genetic or environmental in origin, with little support for causal influences. Causal influences, in isolation or in conjunction with predispositional factors, may exist for other brain regions (eg, ventral striatum) or at more severe levels of cannabis involvement and deserve further study.

Dataset Information

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

Publications

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

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