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Genetic variants in the ErbB4 gene are associated with white matter integrity
Authors:Riccardo Zuliani  T William J MoorheadMark E Bastin  Eve C JohnstoneStephen M Lawrie  Paolo Brambilla  Michael C O'DonovanMichael J Owen  Jeremy HallAndrew M McIntosh
Institution:
  • a Inter-University Centre for Behavioural Neurosciences, DPMSC, Section of Psychiatry, University of Udine, Udine, Italy
  • b Division of Psychiatry, University of Edinburgh, Kennedy Tower, Royal Edinburgh Hospital, Edinburgh, UK
  • c Medical and Radiological Sciences (Medical Physics), University of Edinburgh, Edinburgh, UK
  • d SINAPSE Collaboration, SFC Brain Imaging Research Centre, University of Edinburgh, Edinburgh, UK
  • e Scientific Institute IRCCS ‘E.Medea’, Udine, Italy
  • f MRC Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, UK
  • Abstract:Variations in the signalling NRG1-ErbB4 pathway have been associated with genetic susceptibility for both bipolar disorder and schizophrenia, although the underlying neural mechanisms are still uncertain. Reduced integrity of the anterior limb of the internal capsule (ALIC) has been found in association with risk-associated genetic variation in the 5′ region of the NRG1 gene. We hypothesised that variation in the gene encoding the NRG1 receptor, ErbB4, would also be associated with reduced ALIC integrity and with cognitive impairments characteristic of individuals with bipolar disorder and schizophrenia. Using diffusion tensor imaging (DTI), we examined the white matter integrity associations of the ErbB4 polymorphism rs4673628, which resides within intron 12 of the gene encoding ErbB4, in 36 healthy individuals. We also sought to clarify the cognitive effects of any findings. We found that genetic variation at the rs4673628 locus in the ErbB4 gene was significantly associated with ALIC white matter integrity which was also significantly and positively associated with mnemonic function. These findings provide further evidence to support a key role of NRG1-ErbB4 signalling in the pathophysiology of major mental disorders.
    Keywords:ErbB4  NRG1  Diffusion tensor imaging  Magnetic resonance imaging  Voxel based morphometry  Anterior limb of internal capsule
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