Home > Articles > Published articles > The Influence of DAT1, COMT, and BDNF Genetic Polymorphisms on Total and Subregional Hippocampal Volumes in Early Onset Heavy Cannabis Users |
Date: | 2018 |
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. |
Grants: | Agència de Gestió d'Ajuts Universitaris i de Recerca 2009-SGR-1435 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014-SGR-1411 Instituto de Salud Carlos III RD16-0017-0010 Instituto de Salud Carlos III CPII16-00048 |
Note: | Altres ajuts: SB has been funded by the National Insitute for Health Research (NIHR), UK through a Clinician Scientist award (NIHR-CS-11-001) and also received support from the Medical Research Council (MRC), UK (MR/J012149/1; MC_PC_14105 v.2). JAC is recipient of Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (CNPq, Brazil) productivity. |
Note: | Altres ajuts: MSCBS/PNSD PI101-2006 |
Note: | Altres ajuts: MSCBS/PNSD PI041731-2011 |
Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. |
Language: | Anglès |
Document: | Article ; recerca ; Versió publicada |
Subject: | Brain-derived neurotrophic factor ; Cannabis ; Catechol-O-methyltransferase gene ; Dopamine transporter gene ; Hippocampal subfields ; Hippocampus |
Published in: | Cannabis and Cannabinoid Research, Vol. 3 (february 2018) , p. 1-10, ISSN 2378-8763 |
10 p, 762.5 KB |