Abstract
Introduction: Hippocampal neuroanatomy is affected by genetic variations in dopaminergic candidate genes and environmental insults, such as early onset of chronic cannabis exposure. Here, we examine how hippocampal total and subregional volumes are affected by cannabis use and functional polymorphisms of dopamine-relevant genes, including the catechol-O-methyltransferase (COMT), dopamine transporter (DAT1), and the brain-derived neurotrophic factor (BDNF) genes.Material and Methods: We manually traced total hippocampal volumes and automatically segmented hippocampal subregions using high-resolution MRI images, and performed COMT, DAT1, and BDNF genotyping in 59 male Caucasian young adults aged 18–30 years. These included 30 chronic cannabis users with early-onset (regular use at <16 years) and 29 age-, education-, and intelligence-matched controls.Results: Cannabis use and dopaminergic gene polymorphism had both distinct and interactive effects on the hippocampus. We found emerging alterations of hippocampal total and specific subregional volumes in cannabis users relative to controls (i.e., CA1, CA2/3, and CA4), and associations between cannabis use levels and total and specific subregional volumes. Furthermore, total hippocampal volume and the fissure subregion were affected by cannabis×DAT1 polymorphism (i.e., 9/9R and in 10/10R alleles), reflecting high and low levels of dopamine availability.Conclusion: These findings suggest that cannabis exposure alters the normal relationship between DAT1 polymorphism and the anatomy of total and subregional hippocampal volumes, and that specific hippocampal subregions may be particularly affected.
Highlights
Hippocampal neuroanatomy is affected by genetic variations in dopaminergic candidate genes and environmental insults, such as early onset of chronic cannabis exposure
We have only considered the effect of cannabis use and genetic polymorphism on hippocampus volume, genetic predisposition may interact with cannabis use to affect the neuroanatomy of other subcortical structures,[84] and should be considered in future studies
Our findings suggest that cannabis alone may subtly affect hippocampal neuroanatomy, given the trend-level and dose-dependent reduction observed in cannabis users, the interaction between cannabis and DAT1 polymorphism was a stronger predictor of hippocampal volume differences between cannabis users and controls
Summary
Hippocampal neuroanatomy is affected by genetic variations in dopaminergic candidate genes and environmental insults, such as early onset of chronic cannabis exposure. Cannabis is regularly used by *23 million individuals globally.[1] Regular cannabis use may be detrimental to the brain,[2] being associated with neuropsychological, emotional, and motivational impairments.[3,4] The hippocampus in particular may be especially sensitive to the impact of heavy cannabis use, given its high concentration of cannabinoid receptors type 1 (CB1).[5,6,7] This is evidenced by neuroimaging results of dosedependent hippocampal volume reductions in regular cannabis users.[8,9,10,11] hippocampal alteration has not been consistently observed across studies.[2,12,13,14,15,16,17,18] It remains unclear why hippocampus volumetric reduction has not been consistently observed in cannabis users, some evidence suggests that noncannabis-specific vulnerability factors including dopamine gene polymorphism may have played a role in this heterogeneity.[19,20] Importantly, dopamine gene polymorphism may contribute to adverse mental health outcomes in cannabis users.[21,22,23,24] Given the rising prevalence of cannabis use, treatment seekers, and the global trends toward decriminalization of cannabis products, it is vital to address the heterogeneity in cannabis use-related effects across users, by examining the contribution of dopamine gene polymorphism and cannabis use on hippocampal morphology.[1]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call