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. 2018 Feb 1;3(1):1-10.
doi: 10.1089/can.2017.0021. eCollection 2018.

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

Albert Batalla  1   2   3 , Valentina Lorenzetti  4   5 , Yann Chye  5 , Murat Yücel  5 , Carles Soriano-Mas  6 , Sagnik Bhattacharyya  7 , Marta Torrens  8 , José A S Crippa  9   10 , Rocío Martín-Santos  1   8   9   10
Affiliations

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

Albert Batalla et al. Cannabis Cannabinoid Res. .

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.

Keywords: brain-derived neurotrophic factor; cannabis; catechol-O-methyltransferase gene; dopamine transporter gene; hippocampal subfields; hippocampus.

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Conflict of interest statement

JAC is co-inventor (Mehoulam R, JC, Guimaraes FS, AZ, JH, Breuer A) of the patent “Fluorinated CBD compounds, compositions and uses thereof. Pub. No.: WO/2014/108899. International Application No.: PCT/IL2014/050023” Def. US no. Reg. 62193296; 29/07/2015; INPI on 19/08/2015 (BR1120150164927). The University of São Paulo has licensed the patent to phytecs Pharm (USP Resolution No. 15.1.130002.1.1). The University of São Paulo has an agreement with Prati-Donaduzzi (Toledo, Brazil) to “develop a pharmaceutical product containing synthetic cannabidiol and prove its safety and therapeutic efficacy in the treatment of epilepsy, schizophrenia, Parkinson's disease, and anxiety disorders”. JAC has received travel support from and is medical advisor of BSPG-Pharm. For all other authors, no competing financial interests exist.

Figures

<b>FIG. 1.</b>
FIG. 1.
Hippocampal volumes by DAT1 polymorphism variants (10/10R and 9/9R) in controls (HC) and cannabis users (CB), with larger volumes in HC 10/10R carriers relative to CB 10/10R and CB 9/9R carriers; smaller volumes in HC 9/9R carriers versus CB 9/9R carriers and HC 10/10R carriers.
See this image and copyright information in PMC

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