Format

Send to

Choose Destination
Eur Arch Psychiatry Clin Neurosci. 2019 Jan 3. doi: 10.1007/s00406-018-0977-0. [Epub ahead of print]

Analysis of KCNH2 and CACNA1C schizophrenia risk genes on EEG functional network modulation during an auditory odd-ball task.

Author information

1
Psychiatry Department, School of Medicine, University of Valladolid, Av. Ramón y Cajal, 7, 47005, Valladolid, Spain. alba.lubeiro@gmail.com.
2
FIDMAG Germanes Hospitalàries Research Foundation, Carrer Del Dr. Antoni Pujadas, 38 Sant Boi De Llobregat, 08830, Barcelona, Spain. mfatjo-vilas@fidmag.com.
3
Departament de Biologia Evolutiva, Ecologia i Ciències Ambientals, Facultat de Biologia, Universitat de Barcelona, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Spain. mfatjo-vilas@fidmag.com.
4
CIBERSAM (Biomedical Research Network in Mental Health; Instituto de Salud Carlos III), Madrid, Spain. mfatjo-vilas@fidmag.com.
5
FIDMAG Germanes Hospitalàries Research Foundation, Carrer Del Dr. Antoni Pujadas, 38 Sant Boi De Llobregat, 08830, Barcelona, Spain.
6
Departament de Biologia Evolutiva, Ecologia i Ciències Ambientals, Facultat de Biologia, Universitat de Barcelona, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Spain.
7
CIBERSAM (Biomedical Research Network in Mental Health; Instituto de Salud Carlos III), Madrid, Spain.
8
Biomedical Engineering Group, Department TSCIT, ETS Ingenieros de Telecomunicación, University of Valladolid, Valladolid, Spain.
9
Neurophysiology service, University Hospital of Valladolid, Valladolid, Spain.
10
Neurosciences Institute of Castilla y León (INCYL), University of Salamanca, Pintor Fernando Gallego, 1, 37007, Salamanca, Spain.
11
IMUVA, Mathematics Research Institute, University of Valladolid, Valladolid, Spain.
12
Achucarro Basque Center for Neurosciences, CIBERNED and Departamento de Neurociencias, Universidad del País Vasco, Leioa, Spain.
13
Psychiatry service, University Hospital of Valladolid, Valladolid, Spain.
14
Psychiatry Department, University Hospital of Álava, Álava, Spain.
15
Psychiatry Department, School of Medicine, University of Valladolid, Av. Ramón y Cajal, 7, 47005, Valladolid, Spain.

Abstract

A deficit in task-related functional connectivity modulation from electroencephalogram (EEG) has been described in schizophrenia. The use of measures of neuronal connectivity as an intermediate phenotype may allow identifying genetic factors involved in these deficits, and therefore, establishing underlying pathophysiological mechanisms. Genes involved in neuronal excitability and previously associated with the risk for schizophrenia may be adequate candidates in relation to functional connectivity alterations in schizophrenia. The objective was to study the association of two genes of voltage-gated ion channels (CACNA1C and KCNH2) with the functional modulation of the cortical networks measured with EEG and graph-theory parameter during a cognitive task, both in individuals with schizophrenia and healthy controls. Both CACNA1C (rs1006737) and KCNH2 (rs3800779) were genotyped in 101 controls and 50 schizophrenia patients. Small-world index (SW) was calculated from EEG recorded during an odd-ball task in two different temporal windows (pre-stimulus and response). Modulation was defined as the difference in SW between both windows. Genetic, group and their interaction effects on SW in the pre-stimulus window and in modulation were evaluated using ANOVA. The CACNA1C genotype was not associated with SW properties. KCNH2 was significantly associated with SW modulation. Healthy subjects showed a positive SW modulation irrespective of the KCNH2 genotype, whereas within patients allele-related differences were observed. Patients carrying the KCNH2 risk allele (A) presented a negative SW modulation and non-carriers showed SW modulation similar to the healthy subjects. Our data suggest that KCNH2 genotype contributes to the efficient modulation of brain electrophysiological activity during a cognitive task in schizophrenia patients.

KEYWORDS:

CACNA1C; Electroencephalography; KCNH2; Schizophrenia; Small-world

PMID:
30607529
DOI:
10.1007/s00406-018-0977-0

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center