PMID- 29404409 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220129 IS - 2578-5125 (Print) IS - 2378-8763 (Electronic) IS - 2378-8763 (Linking) VI - 3 IP - 1 DP - 2018 TI - The Influence of DAT1, COMT, and BDNF Genetic Polymorphisms on Total and Subregional Hippocampal Volumes in Early Onset Heavy Cannabis Users. PG - 1-10 LID - 10.1089/can.2017.0021 [doi] AB - 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 cannabisxDAT1 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. FAU - Batalla, Albert AU - Batalla A AD - Department of Psychiatry, Clinical Institute of Neuroscience, Hospital Clinic, IDIBAPS, CIBERSAM and Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Barcelona, Spain. AD - Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands. AD - Nijmegen Institute for Scientist-Practitioners in Addiction (NISPA), Radboud University, Nijmegen, The Netherlands. FAU - Lorenzetti, Valentina AU - Lorenzetti V AD - School of Psychological Sciences, Institute of Psychology Health and Society, The University of Liverpool, Liverpool, United Kingdom. AD - Laboratory for Brain and Mental Health, Monash Institute of Cognitive and Clinical Neurosciences and School of Psychological Sciences, Monash University, Clayton, VIC, Australia. FAU - Chye, Yann AU - Chye Y AD - Laboratory for Brain and Mental Health, Monash Institute of Cognitive and Clinical Neurosciences and School of Psychological Sciences, Monash University, Clayton, VIC, Australia. FAU - Yucel, Murat AU - Yucel M AD - Laboratory for Brain and Mental Health, Monash Institute of Cognitive and Clinical Neurosciences and School of Psychological Sciences, Monash University, Clayton, VIC, Australia. FAU - Soriano-Mas, Carles AU - Soriano-Mas C AD - Department of Psychiatry, Bellvitge University Hospital-IDIBELL, CIBERSAM G-17, and Department of Psychobiology and Methodology in Health Sciences, Universitat Autonoma de Barcelona, Barcelona, Spain. FAU - Bhattacharyya, Sagnik AU - Bhattacharyya S AD - Department of Psychosis Studies, King's College London, Institute of Psychiatry, Psychology and Neuroscience, London, United Kingdom. FAU - Torrens, Marta AU - Torrens M AD - Institute of Neuropsychiatry and Addictions, Hospital del Mar, IMIM (Institut Hospital del Mar d'Investigacions Mediques), Psychiatric Department of Universitat Autonoma de Barcelona, Barcelona, Spain. FAU - Crippa, Jose A S AU - Crippa JAS AD - Department of Neuroscience and Behavior, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil. AD - Instituto Nacional de Ciencia e Tecnologia Translacional em Medicina Translational Medicine (INCT-TM), National Council for Scientific and Technological Development, Sao Paulo, Brazil. FAU - Martin-Santos, Rocio AU - Martin-Santos R AD - Department of Psychiatry, Clinical Institute of Neuroscience, Hospital Clinic, IDIBAPS, CIBERSAM and Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Barcelona, Spain. AD - Institute of Neuropsychiatry and Addictions, Hospital del Mar, IMIM (Institut Hospital del Mar d'Investigacions Mediques), Psychiatric Department of Universitat Autonoma de Barcelona, Barcelona, Spain. AD - Department of Neuroscience and Behavior, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil. AD - Instituto Nacional de Ciencia e Tecnologia Translacional em Medicina Translational Medicine (INCT-TM), National Council for Scientific and Technological Development, Sao Paulo, Brazil. LA - eng GR - MC_PC_14105/MRC_/Medical Research Council/United Kingdom GR - NIHR-CS-011-001/DH_/Department of Health/United Kingdom PT - Journal Article DEP - 20180201 PL - United States TA - Cannabis Cannabinoid Res JT - Cannabis and cannabinoid research JID - 101684827 PMC - PMC5797324 OTO - NOTNLM OT - brain-derived neurotrophic factor OT - cannabis OT - catechol-O-methyltransferase gene OT - dopamine transporter gene OT - hippocampal subfields OT - hippocampus COIS- 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 Sao Paulo has licensed the patent to phytecs Pharm (USP Resolution No. 15.1.130002.1.1). The University of Sao 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. EDAT- 2018/02/07 06:00 MHDA- 2018/02/07 06:01 PMCR- 2018/02/01 CRDT- 2018/02/07 06:00 PHST- 2018/02/07 06:00 [entrez] PHST- 2018/02/07 06:00 [pubmed] PHST- 2018/02/07 06:01 [medline] PHST- 2018/02/01 00:00 [pmc-release] AID - 10.1089/can.2017.0021 [pii] AID - 10.1089/can.2017.0021 [doi] PST - epublish SO - Cannabis Cannabinoid Res. 2018 Feb 1;3(1):1-10. doi: 10.1089/can.2017.0021. eCollection 2018.