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Functional genetic variation of the cannabinoid receptor 1 and cannabis use interact on prefrontal connectivity and related working memory behavior.
Neuropsychopharmacology. 2015 Feb; 40(3):640-9.N

Abstract

Cannabinoid signaling is involved in different brain functions and it is mediated by the cannabinoid receptor 1 (CNR1), which is encoded by the CNR1 gene. Previous evidence suggests an association between cognition and cannabis use. The logical interaction between genetically determined cannabinoid signaling and cannabis use has not been determined. Therefore, we investigated whether CNR1 variation predicts CNR1 prefrontal mRNA expression in postmortem prefrontal human tissue. Then, we studied whether functional variation in CNR1 and cannabis exposure interact in modulating prefrontal function and related behavior during working memory processing. Thus, 208 healthy subjects (113 males) were genotyped for the relevant functional SNP and were evaluated for cannabis use by the Cannabis Experience Questionnaire. All individuals performed the 2-back working memory task during functional magnetic resonance imaging. CNR1 rs1406977 was associated with prefrontal mRNA and individuals carrying a G allele had reduced CNR1 prefrontal mRNA levels compared with AA subjects. Moreover, functional connectivity MRI demonstrated that G carriers who were also cannabis users had greater functional connectivity in the left ventrolateral prefrontal cortex and reduced working memory behavioral accuracy during the 2-back task compared with the other groups. Overall, our results indicate that the deleterious effects of cannabis use are more evident on a specific genetic background related to its receptor expression.

Authors+Show Affiliations

1] Group of Psychiatric Neuroscience, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari 'Aldo Moro', Bari, Italy [2] Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK.Group of Psychiatric Neuroscience, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari 'Aldo Moro', Bari, Italy.1] Group of Psychiatric Neuroscience, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari 'Aldo Moro', Bari, Italy [2] Psychiatric, Clinical Psychology and Psychiatric Rehabilitation Unit, Department of General and Experimental Medicine, University of Perugia, Perugia, Italy.Group of Psychiatric Neuroscience, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari 'Aldo Moro', Bari, Italy.Group of Psychiatric Neuroscience, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari 'Aldo Moro', Bari, Italy.Group of Psychiatric Neuroscience, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari 'Aldo Moro', Bari, Italy.Group of Psychiatric Neuroscience, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari 'Aldo Moro', Bari, Italy.1] Group of Psychiatric Neuroscience, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari 'Aldo Moro', Bari, Italy [2] Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.Group of Psychiatric Neuroscience, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari 'Aldo Moro', Bari, Italy.1] Group of Psychiatric Neuroscience, Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari 'Aldo Moro', Bari, Italy [2] pRED, NORD DTA, F. Hoffman-La Roche Ltd, Basel, Switzerland.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

25139064

Citation

Colizzi, Marco, et al. "Functional Genetic Variation of the Cannabinoid Receptor 1 and Cannabis Use Interact On Prefrontal Connectivity and Related Working Memory Behavior." Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, vol. 40, no. 3, 2015, pp. 640-9.
Colizzi M, Fazio L, Ferranti L, et al. Functional genetic variation of the cannabinoid receptor 1 and cannabis use interact on prefrontal connectivity and related working memory behavior. Neuropsychopharmacology. 2015;40(3):640-9.
Colizzi, M., Fazio, L., Ferranti, L., Porcelli, A., Masellis, R., Marvulli, D., Bonvino, A., Ursini, G., Blasi, G., & Bertolino, A. (2015). Functional genetic variation of the cannabinoid receptor 1 and cannabis use interact on prefrontal connectivity and related working memory behavior. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, 40(3), 640-9. https://doi.org/10.1038/npp.2014.213
Colizzi M, et al. Functional Genetic Variation of the Cannabinoid Receptor 1 and Cannabis Use Interact On Prefrontal Connectivity and Related Working Memory Behavior. Neuropsychopharmacology. 2015;40(3):640-9. PubMed PMID: 25139064.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Functional genetic variation of the cannabinoid receptor 1 and cannabis use interact on prefrontal connectivity and related working memory behavior. AU - Colizzi,Marco, AU - Fazio,Leonardo, AU - Ferranti,Laura, AU - Porcelli,Annamaria, AU - Masellis,Rita, AU - Marvulli,Daniela, AU - Bonvino,Aurora, AU - Ursini,Gianluca, AU - Blasi,Giuseppe, AU - Bertolino,Alessandro, Y1 - 2014/08/20/ PY - 2014/03/21/received PY - 2014/06/29/revised PY - 2014/07/14/accepted PY - 2014/8/21/entrez PY - 2014/8/21/pubmed PY - 2016/3/16/medline SP - 640 EP - 9 JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JO - Neuropsychopharmacology VL - 40 IS - 3 N2 - Cannabinoid signaling is involved in different brain functions and it is mediated by the cannabinoid receptor 1 (CNR1), which is encoded by the CNR1 gene. Previous evidence suggests an association between cognition and cannabis use. The logical interaction between genetically determined cannabinoid signaling and cannabis use has not been determined. Therefore, we investigated whether CNR1 variation predicts CNR1 prefrontal mRNA expression in postmortem prefrontal human tissue. Then, we studied whether functional variation in CNR1 and cannabis exposure interact in modulating prefrontal function and related behavior during working memory processing. Thus, 208 healthy subjects (113 males) were genotyped for the relevant functional SNP and were evaluated for cannabis use by the Cannabis Experience Questionnaire. All individuals performed the 2-back working memory task during functional magnetic resonance imaging. CNR1 rs1406977 was associated with prefrontal mRNA and individuals carrying a G allele had reduced CNR1 prefrontal mRNA levels compared with AA subjects. Moreover, functional connectivity MRI demonstrated that G carriers who were also cannabis users had greater functional connectivity in the left ventrolateral prefrontal cortex and reduced working memory behavioral accuracy during the 2-back task compared with the other groups. Overall, our results indicate that the deleterious effects of cannabis use are more evident on a specific genetic background related to its receptor expression. SN - 1740-634X UR - https://www.unboundmedicine.com/medline/citation/25139064/Functional_genetic_variation_of_the_cannabinoid_receptor_1_and_cannabis_use_interact_on_prefrontal_connectivity_and_related_working_memory_behavior_ L2 - http://dx.doi.org/10.1038/npp.2014.213 DB - PRIME DP - Unbound Medicine ER -