A neuregulin 1 variant is associated with increased lateral ventricle volume in patients with first-episode schizophrenia.
BACKGROUND
Structural brain abnormalities are already present at early phases of psychosis and might be the consequence of neurodevelopmental deviance. Neuregulin 1 gene (NRG1) is a candidate gene for schizophrenia, and its protein has different roles in nervous system development and plasticity. A single nucleotide polymorphism (SNP) within NRG1, SNP8NRG243177, has been associated with brain function among healthy and high-risk subjects and with reduced cell migration among patients with schizophrenia. We examined whether variations in this polymorphism influence brain volumes in first-episode schizophrenia subjects.


METHODS
Ninety-five minimally medicated patients experiencing their first episode of schizophrenia underwent genotyping of three SNPs within the NRG1 gene and structural brain magnetic resonance imaging (MRI). A comparison of volumes of lobar gray matter (GM), lateral ventricles, and cortical cerebrospinal fluid (CSF) was made between the groups according to their genotype after controlling for total intracranial volume.


RESULTS
The SNP8NRG243177 risk T allele was significantly associated, in an allele copy number-dependent fashion, with increased lateral ventricle volume. Genotype explained 7% of the variance of lateral ventricle volume. No significant differences in GM lobar or cortical CSF volumes were found among subgroups.


CONCLUSIONS
Our findings suggest that genetic variations of the NRG1 gene can contribute to the enlargement of the lateral ventricles described in early phases of schizophrenia. These results suggest novel lines of research into potential mechanisms by which schizophrenia susceptibility genes might exert their effect on brain structure.
Mata
Ignacio
I
Department of Psychiatry, School of Medicine, University of Cantabria, University Hospital Marques de Valdecilla, CIBERSAM, Santander, Spain.
Perez-Iglesias
Rocio
R
Roiz-Santiañez
Roberto
R
Tordesillas-Gutierrez
Diana
D
Gonzalez-Mandly
Andres
A
Vazquez-Barquero
Jose Luis
JL
Crespo-Facorro
Benedicto
B
D000328:Adult; D000483:Alleles; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D020547:Lateral Ventricles / Q000473:pathology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020890:Neuregulin-1; D009929:Organ Size; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*
C094131:NRG1 protein, human; D009419:Nerve Tissue Proteins; D020890:Neuregulin-1