Neuregulin-1 (NRG1) polymorphisms linked with psychosis transition are associated with enlarged lateral ventricles and white matter disruption in schizophrenia
Copyright policy )Neuregulin-1 (NRG1) polymorphisms linked with psychosis transition are associated with enlarged lateral ventricles and white matter disruption in schizophrenia
BackgroundTwo single-nucleotide polymorphisms (SNPs) (rs4281084 and rs12155594) within the neuregulin-1 (NRG1) gene have been associated with psychosis transition. However, the neurobiological changes associated with these SNPs remain unclear. We aimed to determine what relationship these two SNPs have on lateral ventricular volume and white matter integrity, as abnormalities in these brain structures are some of the most consistent in schizophrenia.MethodsStructural (n = 370) and diffusion (n = 465) magnetic resonance imaging data were obtained from affected and unaffected individuals predominantly of European descent. The SNPs rs4281084, rs12155594, and their combined allelic load were examined for their effects on lateral ventricular volume, fractional anisotropy (FA) as well as axial (AD) and radial (RD) diffusivity. Additional exploratory analyses assessed NRG1 effects on gray matter volume, cortical thickness, and surface area throughout the brain.ResultsIndividuals with a schizophrenia age of onset ⩽25 and a combined allelic load ⩾3 NRG1 risk alleles had significantly larger right (up to 50%, padj = 0.01) and left (up to 45%, padj = 0.05) lateral ventricle volumes compared with those with allelic loads of less than three. Furthermore, carriers of three or more risk alleles, regardless of age of onset and case status, had significantly reduced FA and elevated RD but stable AD in the frontal cortex compared with those carrying fewer than three risk alleles.ConclusionsOur findings build on a growing body of research supporting the functional importance of genetic variation within the NRG1 gene and complement previous findings implicating the rs4281084 and rs12155594 SNPs as markers for psychosis transition.
- Monash University Australia
- Florey Institute of Neuroscience and Mental Health Australia
- Schizophrenia Research Institute Australia
- Swinburne University of Technology Australia
- University of Melbourne Australia
Adult, Male, Heterozygote, Neuregulin-1, 5202 Biological Psychology, 610, 32 Biomedical and Clinical Sciences, Neuroimaging, anzsrc-for: 1109 Neurosciences, Polymorphism, Single Nucleotide, anzsrc-for: 52 Psychology, anzsrc-for: 32 Biomedical and Clinical Sciences, Lateral Ventricles, 616, Genetics, 2.1 Biological and endogenous factors, Humans, Polymorphism, anzsrc-for: 5203 Clinical and health psychology, Age of Onset, Alleles, Neurosciences, anzsrc-for: 1701 Psychology, Single Nucleotide, Middle Aged, Serious Mental Illness, Mental Illness, Magnetic Resonance Imaging, White Matter, Brain Disorders, Mental Health, anzsrc-for: 3202 Clinical sciences, 52 Psychology, Disease Progression, Schizophrenia, Female, anzsrc-for: 5202 Biological Psychology, Fractional anisotropy, anzsrc-for: 1117 Public Health and Health Services
Adult, Male, Heterozygote, Neuregulin-1, 5202 Biological Psychology, 610, 32 Biomedical and Clinical Sciences, Neuroimaging, anzsrc-for: 1109 Neurosciences, Polymorphism, Single Nucleotide, anzsrc-for: 52 Psychology, anzsrc-for: 32 Biomedical and Clinical Sciences, Lateral Ventricles, 616, Genetics, 2.1 Biological and endogenous factors, Humans, Polymorphism, anzsrc-for: 5203 Clinical and health psychology, Age of Onset, Alleles, Neurosciences, anzsrc-for: 1701 Psychology, Single Nucleotide, Middle Aged, Serious Mental Illness, Mental Illness, Magnetic Resonance Imaging, White Matter, Brain Disorders, Mental Health, anzsrc-for: 3202 Clinical sciences, 52 Psychology, Disease Progression, Schizophrenia, Female, anzsrc-for: 5202 Biological Psychology, Fractional anisotropy, anzsrc-for: 1117 Public Health and Health Services
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).9 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Average influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!