New insights of the role of the KCNH2 gene in schizophrenia: An fMRI case-control study
Por:
Guardiola-Ripoll M, Almodóvar-Payá C, Lubeiro A, Salvador R, Salgado-Pineda P, Gomar JJ, Guerrero-Pedraza A, Sarró S, Maristany M, Fernández-Linsenbarth I, Hernández-García M, Papiol S, Molina V, Pomarol-Clotet E and Fatjó-Vilas M
Publicada:
1 jul 2022
Ahead of Print:
1 may 2022
Resumen:
The KCNH2 gene, encoding for a subunit of a voltage-gated potassium channel, has been identified as a key element of neuronal excitability and a promising novel therapeutic target for schizophrenia (SZ). Nonetheless, evidence highlighting the role of KCNH2 on cognitive and brain activity phenotypes comes mainly from studies based on healthy controls (HC). Therefore, we aimed to study the role of KCNH2 on the brain functional differences between patients with SZ and HC. The fMRI sample comprised 78 HC and 79 patients with SZ (matched for age, sex and premorbid IQ). We studied the effect of the polymorphism KCNH2-rs3800779 on attention and working memory-related brain activity, evaluated through the N-back task, in regions with detected diagnostic differences (regression model, controlled for age, sex and premorbid IQ, FEAT-FSL). We report a significant diagnosis x KCNH2 interaction on brain activity (1-back vs baseline contrast) at the medial superior prefrontal cortex (Zmax = 3.55, p = 0.00861). In this region, patients with SZ carrying the risk genotype (AA) show a deactivation failure, while HC depict the opposite pattern towards deactivation . The brain region with significant diagnosis x KCNH2 interaction has been previously associated with SZ. The results of this study, in which the role of KCNH2 on fMRI response is analysed for the first time in patients, suggest that KCNH2 variability contributes to inefficient brain activity modulation during the N-back task in affected subjects. These data may pave the way to further understand how KCNH2 genetic variability is related to the pathophysiological mechanisms underlying schizophrenia.(c) 2022 Elsevier B.V. and ECNP. All rights reserved.
Filiaciones:
Guardiola-Ripoll M:
FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain
CIBERSAM (Biomedical Research Network in Mental Health, Instituto de Salud Carlos III), Madrid, Spain
Almodóvar-Payá C:
FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain
CIBERSAM (Biomedical Research Network in Mental Health, Instituto de Salud Carlos III), Madrid, Spain
Lubeiro A:
Psychiatry Department, School of Medicine, University of Valladolid, Valladolid, Spain
Salvador R:
FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain
CIBERSAM (Biomedical Research Network in Mental Health, Instituto de Salud Carlos III), Madrid, Spain
Salgado-Pineda P:
FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain
CIBERSAM (Biomedical Research Network in Mental Health, Instituto de Salud Carlos III), Madrid, Spain
Gomar JJ:
FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain
The Litwin-Zucker Alzheimer's Research Center, NY, United States
Guerrero-Pedraza A:
FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain
Hospital Benito Menni-CASM, Sant Boi de Llobregat, Barcelona, Spain
Sarró S:
FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain
CIBERSAM (Biomedical Research Network in Mental Health, Instituto de Salud Carlos III), Madrid, Spain
Maristany M:
Diagnostic Imaging Department, Hospital Sant Joan de Déu Research Foundation, Barcelona, Spain
Fernández-Linsenbarth I:
Psychiatry Department, School of Medicine, University of Valladolid, Valladolid, Spain
Hernández-García M:
Neurosciences Institute of Castilla y León (INCYL), University of Salamanca, Salamanca, Spain
Papiol S:
CIBERSAM (Biomedical Research Network in Mental Health, Instituto de Salud Carlos III), Madrid, Spain
Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich, Germany
Department of Psychiatry, University Hospital, Ludwig Maximilian University, Munich Germany
Molina V:
Psychiatry Department, School of Medicine, University of Valladolid, Valladolid, Spain
Neurosciences Institute of Castilla y León (INCYL), University of Salamanca, Salamanca, Spain
Psychiatry Service, University Hospital of Valladolid, Valladolid, Spain
Pomarol-Clotet E:
FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain
CIBERSAM (Biomedical Research Network in Mental Health, Instituto de Salud Carlos III), Madrid, Spain
Fatjó-Vilas M:
FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain
CIBERSAM (Biomedical Research Network in Mental Health, Instituto de Salud Carlos III), Madrid, Spain
Departament de Biologia Evolutiva, Ecologia i Ciències Ambientals, Facultat de Biologia, Universitat de Barcelona
Barcelona, Spain. Electronic address:
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