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Brain structural changes in cannabis dependence: association with MAGL.

ABSTRACT: Cannabis use is rising, yet there is poor understanding of biological processes that might link chronic cannabis use to brain structural abnormalities. To lend insight into this topic, we examined white matter microstructural integrity and gray matter cortical thickness/density differences between 89 individuals with cannabis dependence (CD) and 89 matched controls (64 males, 25 females in each group) from the Human Connectome Project. We tested whether cortical patterns for expression of genes relevant for cannabinoid signaling (from Allen Human Brain Atlas postmortem tissue) were associated with spatial patterns of cortical thickness/density differences in CD. CD had lower fractional anisotropy than controls in white matter bundles innervating posterior cingulate and parietal cortex, basal ganglia, and temporal cortex. The CD group also had significantly less gray matter thickness and density in precuneus, relative to controls. Sibling-pair analysis found support for causal and graded liability effects of cannabis on precuneus structure. Spatial patterns of gray matter differences in CD were significantly associated with regional differences in monoacylglycerol lipase (MAGL) expression in postmortem brain tissue, such that regions with higher MAGL expression (but not fatty-acid amide hydrolase or FAAH) were more vulnerable to cortical thinning. In sum, chronic cannabis use is associated with structural differences in white and gray matter, which was most prominent in precuneus and associated white matter tracts. Regions with high MAGL expression, and therefore with potentially physiologically restricted endogenous cannabinoid signaling, may be more vulnerable to the effects of chronic cannabis use on cortical thickness.

SUBMITTER: Manza P

PROVIDER: S-EPMC7200265 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Epidemiological studies show a reciprocal inverse association between cancer and Alzheimer's disease (AD). The common mechanistic theory for this effect posits that cells have an innate tendency toward apoptotic or survival pathways, translating to increased risk for either neurodegeneration or cancer. However, it has been shown that cancer patients experience cognitive dysfunction pre- and post-treatment as well as alterations in cerebral gray matter density (GMD) on MRI. To further investigate these issues, we analyzed the association between cancer history (CA±) and age of AD onset, and the relationship between GMD and CA± status across diagnostic groups in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort study. Data was analyzed from 1609 participants with information on baseline cancer history and AD diagnosis, age of AD onset, and baseline MRI scans. Participants were CA+ (N = 503) and CA- (N = 1106) diagnosed with AD, mild cognitive impairment (MCI), significant memory concerns (SMC), and cognitively normal older adults. As in previous studies, CA+ was inversely associated with AD at baseline (P = 0.025); interestingly, this effect appears to be driven by non-melanoma skin cancer (NMSC), the largest cancer category in this study (P = 0.001). CA+ was also associated with later age of AD onset (P < 0.001), independent of apolipoprotein E (APOE) ?4 allele status, and individuals with two prior cancers had later mean age of AD onset than those with one or no prior cancer (P < 0.001), suggesting an additive effect. Voxel-based morphometric analysis of GMD showed CA+ had lower GMD in the right superior frontal gyrus compared to CA- across diagnostic groups (P crit < 0.001, uncorrected); this cluster of lower GMD appeared to be driven by history of invasive cancer types, rather than skin cancer. Thus, while cancer history is associated with a measurable delay in AD onset independent of APOE ?4, the underlying mechanism does not appear to be cancer-related preservation of GMD.

Project description:ImportanceLong-duration spaceflight induces structural changes in the brain and eye. Identification of an association between cerebral and ocular changes could help determine if there are common or independent causes and inform targeted prevention strategies or treatments.ObjectiveTo determine if there is an association between quantitative changes in intracranial compartment volumes and peripapillary total retinal thickness after spaceflight.Design, setting, and participantsThis cohort study included healthy International Space Station crew members before and immediately after long-duration spaceflight. Data on race were not collected. Analysis was conducted from September to November 2020.ExposuresLong-duration spaceflight (mean [SD], 191 [55] days).Main outcomes and measuresOptical coherence tomography-derived peripapillary total retinal thickness as a quantitative assessment and early sign of optic disc edema and magnetic resonance imaging-derived measures of lateral ventricle volume, white matter volume, and whole brain plus cerebrospinal fluid volume.ResultsIn 19 healthy crew members included in this study (5 women [26.3%], 14 men [73.7%]; mean [SD] age, 45.2 [6.4] years), analyses revealed a positive, although not definitive, association between spaceflight-induced changes in total retinal thickness and lateral ventricle volume (4.7-μm increase in postflight total retinal thickness [95% CI, -1.5 to 10.8 μm; P = .13] per 1-mL postflight increase in lateral ventricle volume). Adjustments for mission duration improved the strength of association (5.1 μm; 95% CI, -0.4 to 10.5 μm; P = .07). No associations were detected between spaceflight-induced changes in total retinal thickness and white matter volume (0.02 μm; 95% CI, -0.5 to 0.5 μm; P = .94) or brain tissue plus cerebrospinal fluid volume, an estimate of intracranial volume (0.02 μm; 95% CI, -0.6 to 0.6 μm; P = .95).Conclusions and relevanceThese results help characterize spaceflight-associated neuro-ocular syndrome and the physiologic associations of headward fluid shifts with outcomes during spaceflight on the central nervous system. The possibly weak association between increased total retinal thickness and lateral ventricle volume suggest that while weightlessness-induced fluid redistribution during spaceflight may be a common stressor to the brain and retina, the development of optic disc edema appears to be uncoupled with changes occurring in the intracranial compartment.

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Brain structural changes in cannabis dependence: association with MAGL.

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