The Influence of DAT1, COMT, and BDNF Genetic Polymorphisms on Total and Subregional Hippocampal Volumes in Early Onset Heavy Cannabis Users



Batalla, Albert, Lorenzetti, Valentina ORCID: 0000-0002-5917-7068, Chye, Yann, Yuecel, Murat, Soriano-Mas, Carles, Bhattacharyya, Sagnik, Torrens, Marta, Crippa, Jose AS and Martin-Santos, Rocio
(2018) The Influence of DAT1, COMT, and BDNF Genetic Polymorphisms on Total and Subregional Hippocampal Volumes in Early Onset Heavy Cannabis Users. CANNABIS AND CANNABINOID RESEARCH, 3 (1). pp. 1-10.

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Abstract

<b>Introduction:</b> 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. <b>Material and Methods:</b> 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. <b>Results:</b> 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., <i>9/9R</i> and in <i>10/10R</i> alleles), reflecting high and low levels of dopamine availability. <b>Conclusion:</b> 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.

Item Type: Article
Uncontrolled Keywords: brain-derived neurotrophic factor, cannabis, catechol-O-methyltransferase gene, dopamine transporter gene, hippocampal subfields, hippocampus
Depositing User: Symplectic Admin
Date Deposited: 28 Mar 2018 14:18
Last Modified: 19 Jan 2023 06:37
DOI: 10.1089/can.2017.0021
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3019567