New findings for the clinical management of patients with schizophrenia

20 de December de 2019

The study of the mechanisms involved in the development and the appearance of the clinical manifestations of schizophrenia can help us improve the clinical capacity in the diagnosis and treatment of this important mental disorder.

Previous publications in a cohort of schizophrenia patients, belonging to the “Program of First Episodes of Psychosis in Cantabria” (PAFIP) developed in the H.U. Marquis de Valdecilla, revealed six genes whose expression was deregulated at the beginning of the disease and after antipsychotic treatment.

New results published in the journal Translational Psychiatry have validated the deregulation of the expression of one of these genes (ADAMTS2) in an independent cohort of PAFIP patients responding to antipsychotic treatment. In addition, in mouse brain, the expression of this gene located in regions related to dopaminergic (mesocorticolimbic) pathways associated with this mental disorder has been observed. Finally, in vitro studies in human neuronal cells have shown an activation of ADAMTS2 dependent on dopamine D1 receptors, through the cAMP / CREB and MAPK / ERK signaling pathways, which could be reversed by specific antipsychotics and inhibitors. of these routes.

The research results place the ADAMTS2 gene and the mechanisms that regulate its expression (CREB) as candidates for biomarkers of the onset of the disease and / or response to drug treatment. Future research could help answer some of the questions of the origin of the disease and / or in the search for new pharmacological targets to improve clinical efficacy.

This publication, innovative in the biochemical study of the disease, is part of the PhD thesis of Dr. Fulgencio Ruso Julve, framed in a translational collaboration between the Psychiatry group, led by Dr. Benedicto Crespo Facorro (HUMV-IDIVAL), and the group of Molecular Mechanisms of Cancer, led by Dr. José P. Vaqué Díez (University of Cantabria-IDIVAL), in whose preparation groups of Cyber in Mental Health (CIBERSAM-ISCIII) have participated.

Ref. Dopaminergic control of ADAMTS2 expression through cAMP/CREB and ERK: molecular effects of antipsychotics.Ruso-Julve F, Pombero A,Pilar-Cuéllar F, García-Díaz N,, Garcia-Lopez R, Juncal-Ruiz M, Castro E, Díaz Á, Vazquez-Bourgón J, García-Blanco A, Garro-Martinez E, Pisonero H, Estirado A, Ayesa-Arriola R, López-Giménez J, Mayor F Jr, Valdizán E,Meana J, Gonzalez-Maeso J, Martínez S, Vaqué JP, Crespo-Facorro B