El gen del receptor cannabinoide tipo 2 se asocia con la comorbilidad entre esquizofrenia y dependencia de cannabis y el gen de la enzima amidohidrolasa de ácidos grasos se asocia con la dependencia de cannabis en población española

Francisco Arias Horcajadas, José Ramón Dávila Piriz, Alba Parra González, Sergio Sánchez Romero, Eva Sánchez-Morla, Israel Ampuero Sánchez, José Antonio Ramos Atance

Resumen


El sistema cannabinoide se ha asociado con varios trastornos psiquiátricos como la esquizofrenia y las adicciones. Diversos estudios han observado que algunos polimorfismos del receptor cannabinoide tipo 2 (CNR2), del receptor cannabinoide tipo 1 (CNR1) y del gen de la enzima amido hidrolasa de ácidos grasos (FAAH) pueden ser factores de riesgo de estos trastornos. Hemos analizado diversos polimorfismos del sistema cannabinoide en pacientes diagnosticados de esquizofrenia sin trastorno por uso de sustancias (n = 379), esquizofrenia con trastorno por uso de cannabis (n = 124), dependientes de cannabis sin psicosis asociada (n = 71) y un grupo de control (316) procedentes de diversos hospitales y centros de asistencia sanitaria españoles. Hemos encontrado una asociación entre los polimorfismos rs35761398 y rs12744386 del CNR2 con la presencia de esquizofrenia y trastorno por uso de cannabis comórbido y una pérdida de heterocigosidad en el polimorfismo rs324420 del gen FAAH con la dependencia de cannabis en población española. Los polimorfismos rs35761398 y rs12744386 en CNR2 son factores de riesgo para esquizofrenia en sujetos dependientes de cannabis. La pérdida de heterocigosidad en el polimorfismo rs324420 en el gen FAAH es un factor de riesgo para la dependencia de cannabis.

 

Palabras clave


Trastorno por uso de cannabis; esquizofrenia; polimorfismos; gen del receptor cannabinoide tipo 2; gen del receptor cannabinoide tipo 1; gen de la enzima amido hidrolasa de ácidos grasos

Texto completo:

PDF PDF (English)

Referencias


Andreasen, N. (1995). Symptoms, signs, and diagnosis of schizophrenia. The Lancet, 346, 477-481. doi:10.1016/s0140-6736(95)91325-4.

Aas, M., Melle, I., Bettella, F., Djurovic, S., Le Hellard, S., Bjella, T., … Tesli, M. (2017). Psychotic patients who used cannabis frequently before illness onset have higher genetic predisposition to schizophrenia than those who did not. Psychological Medicine, 48, 43-49. doi:10.1017/S0033291717001209.

Bae, J. S., Kim, J. Y., Park, B. L., Kim, J. H., Kim, B., Park, C. S., … Woo, S. (2014). Genetic association analysis of CNR1 and CNR2 polymorphisms with schizophrenia in a Korean population. Psychiatric Genetics, 24, 225-229. doi:10.1097/YPG.0000000000000047.

Ballon, N., Leroy, S., Roy, C., Bourdel, M. C., Charles-Nicolas, A., Krebs, M. O. y Poirier, M. F. (2006). (AAT)n repeat in the cannabinoid receptor gene (CNR1): Association with cocaine addiction in an African-Caribbean population. Pharmacogenomics Journal, 6, 126-130. doi:10.1038/sj.tpj.6500352.

Banaszkiewicz, I., Biala, G. y Kruk-Slomka, M. (2020). Contribution of CB2 receptors in schizophrenia-related symptoms in various animal models: Short review. Neuroscience & Biobehavioral Reviews, 114, 158-171. doi:10.1016/j.neubiorev.2020.04.020

Benito, C., Núñez, E., Tolón, R. M., Carrier, E. J., Rábano, A., Hillard, C. J., y Romero, J. (2003). Cannabinoid CB2 receptors and fatty acid amide hydrolase are selectively overexpressed in neuritic plaque-associated glia in Alzheimer’s disease brains. Journal of Neuroscience, 23, 11136-1114. doi:10.1523/JNEUROSCI.23-35-11136.2003.

Benito, C., Kim, W. K., Chavarría, I., Hillard, C. J., Mackie, K., Tolón, R. M., … Romero, J. (2005). A glial endogenous cannabinoid system is upregulated in the brains of macaques with simian immunodeficiency virus-induced encephalitis. Journal of Neuroscience, 23, 11136-11141. doi:10.1523/JNEUROSCI.3923-04.2005.

Bioque, M., Mas, S., Costanzo, M. C., Cabrera, B., Lobo, A., González-Pinto, A., … Balanzá-Martínez, V. (2019). Gene-environment interaction between an endocannabinoid system genetic polymorphism and cannabis use in first episode of psychosis. European Neuropsychopharmacology, 29, 786-794. doi:10.1016/j.euroneuro.2019.04.005.

Boileau, I., Tyndale, R. F., Williams, B., Mansouri, E., Westwood, D. J., Le Foll, B., … Tong, J. (2015). The fatty acid amide hydrolase C385A variant affects brain binding of the positron emission tomography tracer [11C] CURB. Journal of Cerebral Blood Flow and Metabolism, 35, 1237-1240. doi:10.1038/jcbfm.2015.119.

Boileau, I., Mansouri, E., Williams, B., Le Foll, B., Rusjan, P., Mizrahi, R., …. y Tong, J. (2016). Fatty acid amide hydrolase binding in brain of cannabis users: Imaging with the novel radiotracer [11C]CURB. Biological Psychiatry, 80, 691-701. doi:10.1016/j.biopsych.2016.04.012.

Borgan, F., Laurikainen, H., Veronese, M., Marques, T. R., Haaparanta-Solin, M., Solin, O., … Howes, O. (2019). In vivo availability of cannabinoid 1 receptor levels in patients with first-episode psychosis. JAMA Psychiatry, 76, 1074. doi:10.1001/jamapsychiatry.2019.1427.

Cabral, G. A., Raborn, E. S., Griffin, L., Dennis, J. y Marciano-Cabral, F. (2008). CB 2 receptors in the brain: Role in central immune function. British Journal of Pharmacology, 153, 240-251. doi:10.1038/sj.bjp.0707584.

Chavarría-Siles, I., Contreras-Rojas, J., Hare, E., Walss-Bass, C., Quezada, P., Dassori, A., … Escamilla, M. A. (2008). Cannabinoid receptor 1 gene (CNR1) and susceptibility to a quantitative phenotype for hebephrenic schizophrenia. American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, 147B, 279-284. doi:10.1002/ajmg.b.30592.

Comings, D. E., Muhleman, D., Gade, R., Johnson, P., Verde, R., Saucier, G. y MacMurray, J. (1997). Cannabinoid receptor gene (CNR1): Association with IV drug use. Molecular Psychiatry, 2, 161-168. doi:10.1038/sj.mp.4000247.

Covault, J., Gelernter, J. y Kranzler, H. (2001). Association study of cannabinoid receptor gene (CNR1) alleles and drug dependence. Molecular Psychiatry, 6, 501-502. doi:10.1038/sj.mp.4000925.

D’Addario, C., Micale, V., Di Bartolomeo, M., Stark, T., Pucci, M., Sulcova, A., … Dell’Osso, B. (2017). A preliminary study of endocannabinoid system regulation in psychosis: Distinct alterations of CNR1 promoter DNA methylation in patients with schizophrenia. Schizophrenia Research, 188, 132-140. doi:10.1016/j.schres.2017.01.022.

Dawson, E. (1995). Identification of a highly polymorphic triplet repeat marker for the brain cannabinoid receptor gene: Use in linkage and association studies of schizophrenia. Schizophrenia Research, 15, 37. doi:10.1016/0920-9964(95)95120-x.

De Almeida, V., y Martins-de-Souza, D. (2018). Cannabinoids and glial cells: possible mechanism to understand schizophrenia. European Archives of Psychiatry and Clinical Neuroscience, 268(7), 727-737. https://doi.org/10.1007/s00406-018-0874-6

De Marchi, N., De Petrocellis, L., Orlando, P., Daniele, F., Fezza, F. y Di Marzo, V. (2003). Endocannabinoid signalling in the blood of patients with schizophrenia. Lipids in Health and Disease, 2, 5. doi:10.1186/1476-511X-2-1.

Deutsch, D. G., Ueda, N. y Yamamoto, S. (2002). The fatty acid amide hydrolase (FAAH). Prostaglandins Leukotrienes and Essential Fatty Acids, 66, 201-210. doi:10.1054/plef.2001.0358.

Dong, M., Lu, L., Zhang, L., Zhang, Y. S., Ng, C. H., Ungvari, G. S., … Xiang, Y. T. (2019). Quality of life in schizophrenia: A meta-analysis of comparative studies. Psychiatric Quarterly, 90, 519-532. doi:10.1007/s11126-019-09633-4.​

Fakhoury, M. (2017). Role of the endocannabinoid system in the pathophysiology of schizophrenia. Molecular Neurobiology, 54, 768-778. doi:10.1007/s12035-016-9697-5.

Falenski, K. W., Thorpe, A. J., Schlosburg, J. E., Cravatt, B. F., Abdullah, R. A., Smith, T. H., … Sim-Selley, L. J. (2010). FAAH/Mice display differential tolerance, dependence, and cannabinoid receptor adaptation after δ 9-tetrahydrocannabinol and anandamide administration. Neuropsychopharmacology, 35, 1775-1787. doi:10.1038/npp.2010.44.

Fezza, F., De Simone, C., Amadio, D. y Maccarrone, M. (2008). Fatty acid amide hydrolase: A gate-keeper of the endocannabinoid system. Sub-Cellular Biochemistry, 49, 101-132. doi:10.1007/978-1-4020-8831-5_4.

Filbey, F. M., Schacht, J. P., Myers, U. S., Chavez, R. S. y Hutchison, K. E. (2010). Individual and additive effects of the CNR1 and FAAH genes on brain response to marijuana cues. Neuropsychopharmacology, 35, 967-975. doi:10.1038/npp.2009.200.

Flanagan, J. M., Gerber, A. L., Cadet, J. L., Beutler, E. y Sipe, J. C. (2006). The fatty acid amide hydrolase 385 A/A (P129T) variant: Haplotype analysis of an ancient missense mutation and validation of risk for drug addiction. Human Genetics, 120, 581-588. doi:10.1007/s00439-006-0250-x.

Fonseca-Pedrero, E., Lucas-Molina, B., Pérez-Albéniz, A., Inchausti, F. y Ortuño-Sierra, J. (2019). Experiencias psicóticas atenuadas y consumo de cannabis en adolescentes de la población general. Adicciones, 32, 41. doi:10.20882/adicciones.1149.

French, L., Gray, C., Leonard, G., Perron, M., Pike, G. B., Richer, L., … Paus, T. (2015). Early cannabis use, polygenic risk score for schizophrenia, and brain maturation in adolescence. JAMA Psychiatry, 72, 1002. doi:10.1001/jamapsychiatry.2015.1131.

Galiègue, S., Mary, S., Marchand, J., Dussossoy, D., Carrière, D., Carayon, P., … Casellas, P. (1995). Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations. European Journal of Biochemistry, 232, 54-61. doi:10.1111/j.1432-1033.1995.tb20780.x.

Galve-Roperh, I., Aguado, T., Palazuelos, J. y Guzman, M. (2008). Mechanisms of control of neuron survival by the endocannabinoid system. Current Pharmaceutical Design, 14, 2279-2288. doi:10.2174/138161208785740117.

García-Álvarez, L., Gomar, J., García-Portilla, M. y Bobes, J. (2019). Consumo de cannabis y alteraciones cognitivas en esquizofrenia y primeros episodios psicóticos. Adicciones, 31, 89-94. doi:10.20882/adicciones.1328.

García-Gutiérrez, M. S., Ortega-Álvaro, A., Busquets-García, A., Pérez-Ortiz, J. M., Caltana, L., Ricatti, M. J., … Manzanares, J. (2013). Synaptic plasticity alterations associated with memory impairment induced by deletion of CB2 cannabinoid receptors. Neuropharmacology, 73, 388-396. doi:10.1016/j.neuropharm.2013.05.034.

Gerra, M. C., Jayanthi, S., Manfredini, M., Walther, D., Schroeder, J., Phillips, K. A., … Donnini, C. (2018). Gene variants and educational attainment in cannabis use: Mediating role of DNA methylation. Translational Psychiatry, 8, 23. doi:10.1038/s41398-017-0087-1.

Gong, J. P., Onaivi, E. S., Ishiguro, H., Liu, Q. R., Tagliaferro, P. A., Brusco, A. y Uhl, G. R. (2006). Cannabinoid CB2 receptors: Immunohistochemical localization in rat brain. Brain Research, 1071, 10-23. doi:10.1016/j.brainres.2005.11.035.

Gouvêa, E. S., Santos, A. F., Ota, V. K., Mrad, V., Gadelha, A., Bressan, R. A., … Belangero, S. I. (2017). The role of the CNR1 gene in schizophrenia: A systematic review including unpublished data. Revista Brasileira de Psiquiatria, 39, 160-171. doi:10.1590/1516-4446-2016-1969.

Hamdani, N., Tabeze, J. P., Ramoz, N., Ades, J., Hamon, M., Sarfati, Y., … Gorwood, P. (2008). The CNR1 gene as a pharmacogenetic factor for antipsychotics rather than a susceptibility gene for schizophrenia. European Neuropsychopharmacology, 18, 34-40. doi:10.1016/j.euroneuro.2007.05.005.

Hariri, A. R., Gorka, A., Hyde, L. W., Kimak, M., Halder, I., Ducci, F., … Manuck, S. B. (2009). Divergent effects of genetic variation in endocannabinoid signaling on human threat- and reward-related brain function. Biological Psychiatry, 66, 9-16. doi:10.1016/j.biopsych.2008.10.047.

Hartman, C. A., Hopfer, C. J., Haberstick, B., Rhee, S. H., Crowley, T. J., Corley, R. P., … Ehringer, M. A. (2009). The association between cannabinoid receptor 1 gene (CNR1) and cannabis dependence symptoms in adolescents and young adults. Drug and Alcohol Dependence, 104, 11-16. doi:10.1016/j.drugalcdep.2009.01.022.

Haughey, H. M., Marshall, E., Schacht, J. P., Louis, A. y Hutchison, K. E. (2008). Marijuana withdrawal and craving: Influence of the cannabinoid receptor 1 (CNR1) and fatty acid amide hydrolase (FAAH) genes. Addiction, 103, 1678-1686. doi:10.1111/j.1360-0443.2008.02292.x.

Heller, D., Schneider, U., Seifert, J., Cimander, K. F. y Stuhrmann, M. (2001). The cannabinoid receptor gene (CNR1) is not affected in German i.v. drug users. Addiction Biology, 6, 183-187. doi:10.1080/13556210020040271.

Herkenham, M., Lynn, A. B., Johnson, M. R., Melvin, L. S., De Costa, B. R. y Rice, K. C. (1991). Characterization and localization of cannabinoid receptors in rat brain: A quantitative in vitro autoradiographic study. Journal of Neuroscience, 11, 563-583. doi:10.1523/jneurosci.11-02-00563.1991.

Hindocha, C., Freeman, T., Bloomfield, M., Bramon, E., Morgan, C. y Curran, H. V. (2019). P.147 Acute effects of cannabinoids on addiction endophenotypes are moderated by genes encoding the cannabinoid receptor 1 and FAAH enzyme. European Neuropsychopharmacology, 29, S116-S117. doi:10.1016/j.euroneuro.2019.09.196.

Hindocha, C., Quattrone, D., Freeman, T. P., Murray, R. M., Mondelli, V., Breen, G., … Di Forti, M. (2020). Do AKT1, COMT and FAAH influence reports of acute cannabis intoxication experiences in patients with first episode psychosis, controls and young adult cannabis users? Translational Psychiatry, 10, 143. doi:10.1038/s41398-020-0823-9.

Ho, B. C., Wassink, T. H., Ziebell, S. y Andreasen, N. C. (2011). Cannabinoid receptor 1 gene polymorphisms and marijuana misuse interactions on white matter and cognitive deficits in schizophrenia. Schizophrenia Research, 128, 66-75. doi:10.1016/j.schres.2011.02.021.

Ishiguro, H., Iwasaki, S., Teasenfitz, L., Higuchi, S., Horiuchi, Y., Saito, T., … Onaivi, E. S. (2007). Involvement of cannabinoid CB2 receptor in alcohol preference in mice and alcoholism in humans. Pharmacogenomics Journal, 7, 380-385. doi:10.1038/sj.tpj.6500431.

Ishiguro, H., Horiuchi, Y., Ishikawa, M., Koga, M., Imai, K., Suzuki, Y., … Arinami, T. (2010). Brain cannabinoid CB2 receptor in schizophrenia. Biological Psychiatry, 67, 974-982. doi:10.1016/j.biopsych.2009.09.024.

Javed, H., Azimullah, S., Haque, M. E. y Ojha, S. K. (2016). Cannabinoid type 2 (CB2) receptors activation protects against oxidative stress and neuroinflammation associated dopaminergic neurodegeneration in rotenone model of parkinson’s disease. Frontiers in Neuroscience, 10, 321. doi:10.3389/fnins.2016.00321.

Juckel, G., Manitz, M. P., Brüne, M., Friebe, A., Heneka, M. T. y Wolf, R. J. (2011). Microglial activation in a neuroinflammational animal model of schizophrenia - a pilot study. Schizophrenia Research, 131, 96-100. doi:10.1016/j.schres.2011.06.018.

Kay, S. R., Fiszbein, A. y Opler, L. A. (1987). The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bulletin, 13, 261-276.

Kong, W., Li, H., Tuma, R. F. y Ganea, D. (2014). Selective CB2 receptor activation ameliorates EAE by reducing Th17 differentiation and immune cell accumulation in the CNS. Cellular Immunology, 287, 1-17. doi:10.1016/j.cellimm.2013.11.002.

Krebs, M. O., Morvan, Y., Jay, T., Gaillard, R. y Kebir, O. (2014). Psychotomimetic effects at initiation of cannabis use are associated with cannabinoid receptor 1 (CNR1) variants in healthy students. Molecular Psychiatry, 19, 402-403. doi:10.1038/mp.2013.188.

Leroy, S., Griffon, N., Bourdel, M. C., Olié, J. P., Poirier, M. F. y Krebs, M. O. (2001). Schizophrenia and the cannabinoid receptor type 1 (CB1): Association study using a single-base polymorphism in coding exon 1. American Journal of Medical Genetics - Neuropsychiatric Genetics, 105, 749-752. doi:10.1002/ajmg.10038.

Li, T., Liu, X., Zhu, Z. H., Zhao, J., Hu, X., Ball, D. M., …. Collier, D. A. (2000). No association between (AAT)n repeats in the cannabinoid receptor gene (CNR1) and heroin abuse in a Chinese population. Molecular Psychiatry, 5, 128-130. doi:10.1038/sj.mp.4000670.

Malfitano, A. M., Basu, S., Maresz, K., Bifulco, M. y Dittel, B. N. (2014). What we know and do not know about the cannabinoid receptor 2 (CB2). Seminars in Immunology, 26, 369-379. doi:10.1016/j.smim.2014.04.002.

Manzanares, J., Cabañero, D., Puente, N., García-Gutiérrez, M. S., Grandes, P. y Maldonado, R. (2018). Role of the endocannabinoid system in drug addiction. Biochemical Pharmacology, 157, 108-121. doi:10.1016/j.bcp.2018.09.013.

Marconi, A., Di Forti, M., Lewis, C. M., Murray, R. M. y Vassos, E. (2016). Meta-Analysis of the association between the level of cannabis use and risk of psychosis. Schizophrenia Bulletin, 42, 1262-1269. doi:10.1093/schbul/sbw003.

Martínez-Gras, I., Hoenicka, J., Ponce, G., Rodríguez–Jiménez, R., Jiménez-Arriero, M. A., Pérez-Hernandez, E., … Rubio, G. (2006). (AAT)n repeat in the cannabinoid receptor gene, CNR1: Association with schizophrenia in a Spanish population. European Archives of Psychiatry and Clinical Neuroscience, 256, 437-441. doi:10.1007/s00406-006-0665-3.

Melroy-Greif, W. E., Wilhelmsen, K. C. y Ehlers, C. L. (2016). Genetic variation in FAAH is associated with cannabis use disorders in a young adult sample of Mexican Americans. Drug and Alcohol Dependence, 166, 249-253. doi:10.1016/j.drugalcdep.2016.06.021.

Minichino, A., Senior, M., Brondino, N., Zhang, S. H., Godwlewska, B. R., Burnet, P. W. J., … Lennox, B. R. (2019). Measuring disturbance of the endocannabinoid system in psychosis: A systematic review and meta-analysis. JAMA Psychiatry, 76, 914-923. doi:10.1001/jamapsychiatry.2019.0970.

Morita, Y., Ujike, H., Tanaka, Y., Uchida, N., Nomura, A., Ohtani, K., … Kuroda, S. (2005). A nonsynonymous polymorphism in the human fatty acid amide hydrolase gene did not associate with either methamphetamine dependence or schizophrenia. Neuroscience Letters, 376, 182-187. doi:10.1016/j.neulet.2004.11.050.

Onaivi, E. S., Ishiguro, H., Gong, J. P., Patel, S., Perchuk, A., Meozzi, P. A., … Uhl, G. R. (2006). Discovery of the presence and functional expression of cannabinoid CB2 receptors in brain. Annals of the New York Academy of Sciences, 1074, 514-536. doi:10.1196/annals.1369.052.

Onaivi, E. S., Ishiguro, H., Gu, S. y Liu, Q. R. (2012). CNS effects of CB2 cannabinoid receptors: Beyond neuro-immuno-cannabinoid activity. Journal of Psychopharmacology, 26, 92-103. doi:10.1177/0269881111400652.

Ortega-Alvaro, A., Aracil-Fernández, A., García-Gutiérrez, M. S., Navarrete, F. y Manzanares, J. (2011). Deletion of CB2 cannabinoid receptor induces schizophrenia-related behaviors in mice. Neuropsychopharmacology, 36, 1489-1504. doi:10.1038/npp.2011.34.

Patel, M. M., Nielsen, D. A., Kosten, T. R., De La Garza, R., Newton, T. F. y Verrico, C. D. (2018). FAAH variant Pro129Thr modulates subjective effects produced by cocaine administration. American Journal on Addictions, 27, 567-573. doi: 10.1111/ajad.12788.

Peralta, V. y Cuesta, M. J. (1994). Psychometric properties of the positive and negative syndrome scale (PANSS) in schizophrenia. Psychiatry Research, 53, 31-40.

Peters, B. D., Blaas, J. y de Haan, L. (2010). Diffusion tensor imaging in the early phase of schizophrenia: What have we learned? Journal of Psychiatric Research, 44, 993-1004. doi:10.1016/j.jpsychires.2010.05.003.

Parkar, S. R., Ramanathan, S., Nair, N., Batra, S. A., Adarkar, S. A., Kund, P., … Moghe, S. H. (2011). Are the effects of cannabis dependence on glucose metabolism similar to schizophrenia? An FDG PET understanding. Indian Journal of Psychiatry, 53, 13-20. doi:10.4103/0019-5545.75552.

Rodríguez-Muñoz, M., Sánchez-Blázquez, P., Callado, L. F., Meana, J. J. y Garzón-Niño, J. (2017). Schizophrenia and depression, two poles of endocannabinoid system deregulation. Translational Psychiatry, 7, 1291. doi:10.1038/s41398-017-0029-y.

Rojnic, M., Bosnjak, D., Ganoci, L., Makaric, P., Kekin, I., Rossini, L., … Bozina, N. (2019). Association of CNR1 genotypes with changes in neurocognitive performance after eighteen-month treatment in patients with first-episode psychosis. European Psychiatry, 61, 88-96. doi:10.1016/j.eurpsy.2019.07.004.

Sahu, P., Mudgal, J., Arora, D., Kinra, M., Mallik, S. B., Rao, C. M., … Nampoothiri, M. (2019). Cannabinoid receptor 2 activation mitigates lipopolysaccharide-induced neuroinflammation and sickness behavior in mice. Psychopharmacology, 236, 1829-1838. doi:10.1007/s00213-019-5166-y.

Schacht, J. P., Selling, R. E. y Hutchison, K. E. (2009). Intermediate cannabis dependence phenotypes and the FAAH C385A variant: An exploratory analysis. Psychopharmacology, 203, 511-517. doi:10.1007/s00213-008-1397-z.

Seifert, J., Ossege, S., Emrich, H. M., Schneider, U. y Stuhrmann, M. (2007). No association of CNR1 gene variations with susceptibility to schizophrenia. Neuroscience Letters, 426, 29-33. doi:10.1016/j.neulet.2007.08.008.

Sipe, J. C., Chiang, K., Gerber, A. L., Beutler, E. y Cravatt, B. F. (2002). A missense mutation in human fatty acid amide hydrolase associated with problem drug use. Proceedings of the National Academy of Sciences of the United States of America, 99, 8394-8399. doi:10.1073/pnas.082235799.

Tao, R., Li, C., Jaffe, A., Shin, J., Deep-Soboslay, A., Yamin, R., …. Hyde, T.M. (2020). Cannabinoid receptor CNR1 expression and DNA methylation in human prefrontal cortex, hippocampus and caudate in brain development and schizophrenia. Translational Psychiatry, 10, 158. doi:10.1038/s41398-020-0832-8.

Tong, D., He, S., Wang, L., Jin, L., Si, P. y Cheng, X. (2013). Association of single-nucleotide polymorphisms in the cannabinoid receptor 2 gene with schizophrenia in the Han Chinese population. Journal of Molecular Neuroscience, 51, 454-460. doi:10.1007/s12031-013-0062-0.

Tsai, S. J., Wang, Y. C. y Hong, C. J. (2000). Association study of a cannabinoid receptor gene (CNR1) polymorphism and schizophrenia. Psychiatric Genetics, 10, 149-151. doi:10.1097/00041444-200010030-00008.

Tyndale, R. F., Payne, J. I., Gerber, A. L. y Sipe, J. C. (2007). The fatty acid amide hydrolase C385A (P129T) missense variant in cannabis users: Studies of drug use and dependence in caucasians. American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, 144B, 660-666. doi:10.1002/ajmg.b.30491.

Ujike, H., Takaki, M., Nakata, K., Tanaka, Y., Takeda, T., Kodama, M., … Kuroda, S. (2002). CNR1, central cannabinoid receptor gene, associated with susceptibility to hebephrenic schizophrenia. Molecular Psychiatry, 7, 515-518. doi:10.1038/sj.mp.4001029.

Xi, Z. X., Peng, X. Q., Li, X., Song, R., Zhang, H. Y., Liu, Q. R., … Gardner, E. L. (2011). Brain cannabinoid CB2 receptors modulate cocaine’s actions in mice. Nature Neuroscience, 14, 1160-1166. doi:10.1038/nn.2874.

Van Hell, H. H., Jager, G., Bossong, M. G., Brouwer, A., Jansma, J. M., Zuurman, L., … Ramsey, N. F. (2012). Involvement of the endocannabinoid system in reward processing in the human brain. Psychopharmacology, 219, 981-990. doi:10.1007/s00213-011-2428-8.

Watts, J. J., Jacobson, M. R., Lalang, N., Boileau, I., Tyndale, R. F., Kiang, M., … Mizrahi, R. (2020). Imaging brain fatty acid amide hydrolase in untreated patients with psychosis. Biological Psychiatry, 88, 727-735. doi:10.1016/j.biopsych.2020.03.003.

Zammit, S., Spurlock, G., Williams, H., Norton, N., Williams, N., O’Donovan, M. C., ... Owen, M. J. (2007). Genotype effects of CHRNA7, CNRI and COMT in schizophrenia: Interactions with tobacco and cannabis use. British Journal of Psychiatry, 191, 402-407. doi:10.1192/bjp.bp.107.036129.

Zhang, W., Liu, H., Deng, X., Ma, Y. y Liu, Y. (2020). FAAH levels and its genetic polymorphism association with susceptibility to methamphetamine dependence. Annals of Human Genetics, 84, 259-270. doi:10.1111/ahg.12368.




DOI: https://doi.org/10.20882/adicciones.1587

Enlaces refback

  • No hay ningún enlace refback.