title: Dysregulated peripheral endocannabinoid system signaling is associated with cognitive deficits in first-episode psychosis.
abstract: Among etiological explanations for psychosis, several hypotheses involving alterations on the immune/inflammatory system have been proposed. The endocannabinoid system (ECS) is an endogenous neuroprotective, anti-inflammatory system that modulates cognitive processes. Its altered expression has been associated with psychotic disorders. 73 patients with a first episode of psychoses (FEP) and 67 healthy controls were recruited in 5 university centers in Spain. The protein expression of the main peripheral ECS components was determined in peripheral blood mononuclear cells. The cognition function was assessed following the MATRICS consensus. After controlling for potential confounding factors, working memory statistically correlated to the peripheral N-acyl phosphatidylethanolamine phospholipase expression (p = 0.039). The short-term verbal memory correlated to the Diacylglycerol lipase (p = 0.043) and the fatty acid amide hydrolase (p = 0.026) expression. Finally, attention measures correlated to the Monoacylglycerol lipase expression, by means of the CPT-II commissions (p = 0.036) and detectability (p = 0.026) scores. The ECS may regulate the activation of key mediators in immune and inflammatory responses that may be involved in the primary neuronal stress phenomenon that occurs from the onset of psychotic illness. This study points a relationship between the ECS and the cognitive function in early psychosis and suggests the use of some of the ECS elements as biomarkers and/or pharmacological targets for FEP.
authors.affiliation: Barcelona Clínic Schizophrenia Unit, Neuroscience Institute, Hospital Clínic de Barcelona, Barcelona, Spain. Electronic address: mbioque@clinic.ub.es.
authors.forename: Miquel
authors.initials: M
authors.lastname: Bioque
authors.affiliation: Barcelona Clínic Schizophrenia Unit, Neuroscience Institute, Hospital Clínic de Barcelona, Barcelona, Spain.
authors.forename: Bibiana
authors.initials: B
authors.lastname: Cabrera
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Universidad Complutense de Madrid, Madrid, Spain; Instituto de Investigación, Hospital 12 de Octubre (i+12), Madrid, Spain.
authors.forename: Borja
authors.initials: B
authors.lastname: García-Bueno
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Universidad Complutense de Madrid, Madrid, Spain; Instituto de Investigación, Hospital 12 de Octubre (i+12), Madrid, Spain.
authors.forename: Karina S
authors.initials: KS
authors.lastname: Mac-Dowell
authors.affiliation: Barcelona Bipolar Disorder Program, Neuroscience Institute, Hospital Clínic de Barcelona, Barcelona, Spain.
authors.forename: Carla
authors.initials: C
authors.lastname: Torrent
authors.affiliation: Department of Psychiatry, Faculty of Medicine, University of Oviedo, Instituto Universitario de Neurociencias del Principado de Asturias (INEUROPA), Oviedo, Spain.
authors.forename: Pilar A
authors.initials: PA
authors.lastname: Saiz
authors.affiliation: Child and Adolescent Psychiatry Department, IIS Gregorio Marañón, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Mara
authors.initials: M
authors.lastname: Parellada
authors.affiliation: Hospital Universitario de Álava (sede Santiago), Universidad Nacional de Educación a Distancia, Vitoria, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: González-Pinto
authors.affiliation: Department of Psychiatry, University of Zaragoza and Instituto de Investigación Sanitaria de Aragón, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Lobo
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Universidad Complutense de Madrid, Madrid, Spain; Instituto de Investigación, Hospital 12 de Octubre (i+12), Madrid, Spain.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Leza
authors.affiliation: Barcelona Clínic Schizophrenia Unit, Neuroscience Institute, Hospital Clínic de Barcelona, Barcelona, Spain; Department of Psychiatry and Clinical Psycobiology, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Bernardo
mesh_terms: D000293:Adolescent; D000328:Adult; D000581:Amidohydrolases / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D003072:Cognition Disorders / Q000209:etiology*; D063388:Endocannabinoids / Q000097:blood*; D005260:Female; D006801:Humans; D008071:Lipoprotein Lipase / Q000378:metabolism; D008297:Male; D008570:Memory, Short-Term; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000150:complications*; D015398:Signal Transduction / Q000502:physiology*; D013030:Spain; D013223:Statistics as Topic; D018709:Statistics, Nonparametric; D014706:Verbal Learning; D055815:Young Adult; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D063388:Endocannabinoids; D008071:Lipoprotein Lipase; D000099252:Fatty Acid Amide Hydrolases
keywords: Biomarker; Cognition; Endocannabinoid system; First episode psychosis; Schizophrenia