title: Brain structural and clinical changes after first episode psychosis: Focus on cannabinoid receptor 1 polymorphisms.
abstract: Cannabinoid receptor 1 (CNR1) gene polymorphisms have been associated with central and peripheral effects of cannabis and schizophrenia pathophysiology. Here, we have tested whether three CNR1 variants (rs1049353, rs1535255 and rs2023239) are associated with changes in brain volumes, body mass index (BMI) or psychopathological scores in a 3-year longitudinal study of 65 first-episode psychosis patients. The rs1049353 at-risk allele was significantly associated with a greater reduction of caudate volume, and the rs2023239 T/C polymorphism showed a significant decrease in thalamic volume after the 3-year period. For those who were not cannabis users, the rs1535255 and rs2023239 polymorphisms had effects in lateral ventricle (LV), and LV and white matter, respectively. The rs2023239 variant also was associated with significant improvements in positive and negative symptoms of schizophrenia. There was no significant effect of any of the variants on changes in BMI over the 3-year study. Finally, an interaction between all three polymorphisms was found involving evolution of positive symptoms. These findings suggest that the cannabinoid pathway is associated with schizophrenia evolution over time. However, further studies using larger cohorts are needed to confirm these results. If confirmed, the present findings could lead in subsequent investigations for identification of novel drug targets for improved treatment of patients suffering from schizophrenia.
authors.affiliation: University Hospital Marqués de Valdecilla. Department of Psychiatry, School of Medicine, University of Cantabria, Santander, Spain; CIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Madrid, Spain; IDIVAL, Instituto de Investigación Marqués de Valdecilla, Santander, Spain. Electronic address: p.suarez.pinilla@gmail.com.
authors.forename: Paula
authors.initials: P
authors.lastname: Suárez-Pinilla
authors.affiliation: University Hospital Marqués de Valdecilla. Department of Psychiatry, School of Medicine, University of Cantabria, Santander, Spain; CIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Madrid, Spain; IDIVAL, Instituto de Investigación Marqués de Valdecilla, Santander, Spain.
authors.forename: Roberto
authors.initials: R
authors.lastname: Roiz-Santiañez
authors.affiliation: University Hospital Marqués de Valdecilla. Department of Psychiatry, School of Medicine, University of Cantabria, Santander, Spain; CIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Madrid, Spain; IDIVAL, Instituto de Investigación Marqués de Valdecilla, Santander, Spain.
authors.forename: Víctor
authors.initials: V
authors.lastname: Ortiz-García de la Foz
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, UK.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Guest
authors.affiliation: University Hospital Marqués de Valdecilla. Department of Psychiatry, School of Medicine, University of Cantabria, Santander, Spain; CIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Madrid, Spain; IDIVAL, Instituto de Investigación Marqués de Valdecilla, Santander, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Ayesa-Arriola
authors.affiliation: CIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Madrid, Spain; Departament de Biología Animal, Facultat de Biología, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Aldo
authors.initials: A
authors.lastname: Córdova-Palomera
authors.affiliation: Neuroimaging Unit/Technological Facilities-IDIVAL, Santander, Spain.
authors.forename: Diana
authors.initials: D
authors.lastname: Tordesillas-Gutierrez
authors.affiliation: University Hospital Marqués de Valdecilla. Department of Psychiatry, School of Medicine, University of Cantabria, Santander, Spain; CIBERSAM, Centro Investigación Biomédica en Red Salud Mental, Madrid, Spain; IDIVAL, Instituto de Investigación Marqués de Valdecilla, Santander, Spain.
authors.forename: Benedicto
authors.initials: B
authors.lastname: Crespo-Facorro
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology; D002186:Cannabinoids / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011618:Psychotic Disorders / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics / Q000473:pathology / Q000503:physiopathology
chemical_list: D002186:Cannabinoids; D043884:Receptor, Cannabinoid, CB1
keywords: Biological marker; CNR1 protein; Endophenotypes; Longitudinal studies; Magnetic resonance imaging; Neuroimaging; Schizophrenia