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Peripheral Endocannabinoid System Dysregulation in First-Episode Psychosis

BIOQUE, Miquel ; GARCIA-BUENO, Borja ; BERNARDO, Miguel ; MACDOWELL, Karina S ; MESEGUER, Ana ; SAIZ, Pilar A ; PARELLADA, Mara ; GONZALEZ-PINTO, Ana ; RODRIGUEZ-JIMENEZ, Roberto ; LOBO, Antonio ; LEZA, Juan C

Neuropsychopharmacology (New York, N.Y.), 2013-12, Vol.38 (13), p.2568-2577 [Periódico revisado por pares]

Basingstoke: Nature Publishing Group

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Título:
Peripheral Endocannabinoid System Dysregulation in First-Episode Psychosis
Autor: BIOQUE, Miquel ; GARCIA-BUENO, Borja ; BERNARDO, Miguel ; MACDOWELL, Karina S ; MESEGUER, Ana ; SAIZ, Pilar A ; PARELLADA, Mara ; GONZALEZ-PINTO, Ana ; RODRIGUEZ-JIMENEZ, Roberto ; LOBO, Antonio ; LEZA, Juan C
Assuntos: Adolescent ; Adult ; Adult and adolescent clinical studies ; Amidohydrolases - metabolism ; Biological and medical sciences ; Biomarkers ; Child ; Child & adolescent psychiatry ; Endocannabinoids - metabolism ; Enzymes ; Fatty acids ; Female ; Humans ; Hypotheses ; Leukocytes, Mononuclear - metabolism ; Male ; Marijuana ; Medical sciences ; Monoacylglycerol Lipases - metabolism ; Neurosciences ; Original ; Phospholipase D - metabolism ; Proteins ; Psychiatric Status Rating Scales ; Psychology. Psychoanalysis. Psychiatry ; Psychopathology. Psychiatry ; Psychoses ; Psychosis ; Psychotic Disorders - metabolism ; Psychotic Disorders - pathology ; Receptor, Cannabinoid, CB2 - metabolism ; Schizophrenia ; Young Adult
É parte de: Neuropsychopharmacology (New York, N.Y.), 2013-12, Vol.38 (13), p.2568-2577
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FLAMM-PEPs is a multicentric, collaborative and translational group inside CIBERSAM aimed to study inflammatory pathways in psychosis both as possible biomarkers and as possible new therapeutic targets, incorporated in the PEPs study, a Spanish research project in first episodes of psychosis.
Descrição: Several hypotheses involving alterations of the immune system have been proposed among etiological explanations for psychotic disorders. The endocannabinoid system (ECS) has a homeostatic role as an endogenous neuroprotective and anti-inflammatory system. Alterations of this system have been associated with psychosis. Cannabis use is a robust risk factor for these disorders that could alter the ECS signalling. In this study, 95 patients with a first episode of psychosis (FEP) and 90 healthy controls were recruited. Protein expression of cannabinoid receptor 2 (CB2), the protein levels of the main endocannabinoid synthesizing enzymes N-acyl phosphatidylethanolamine phospholipase (NAPE) and diacylglycerol lipase (DAGL), and of degradation enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) were determined by western blot analysis in peripheral blood mononuclear cells (PBMCs). Patients with a FEP showed a decreased expression of CB2 and of both endocannabinoids synthesizing enzymes (NAPE and DAGL) in comparison to healthy controls. After controlling for age, gender, body mass index, and cannabis use, NAPE and DAGL expression remained significantly decreased, whereas FAAH and MAGL expression were increased. On the other hand, FEP subjects with history of severe cannabis use showed a larger ECS dysregulation compared with healthy controls. These results indicate an ECS dysregulation in PBMC of FEP patients. The alteration of the ECS presented at the initial phases of psychosis could be contributing to the pathophysiology of the disease and constitutes a possible biomarker of psychotic disorders and an interesting pharmacological target to take into account for therapeutic purposes.
Editor: Basingstoke: Nature Publishing Group
Idioma: Inglês

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Peripheral Endocannabinoid System Dysregulation in First-Episode Psychosis

BIOQUE, Miquel ; GARCIA-BUENO, Borja ; BERNARDO, Miguel ; MACDOWELL, Karina S ; MESEGUER, Ana ; SAIZ, Pilar A ; PARELLADA, Mara ; GONZALEZ-PINTO, Ana ; RODRIGUEZ-JIMENEZ, Roberto ; LOBO, Antonio ; LEZA, Juan C

Basingstoke: Nature Publishing Group

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