Genetic variants in the ErbB4 gene are associated with white matter integrity

Riccardo Zuliani, T. William J Moorhead, Mark E. Bastin, Eve C. Johnstone, Stephen M. Lawrie, Paolo Brambilla, Michael C. O'Donovan, Michael J. Owen, Jeremy Hall, Andrew M. McIntosh

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)133-137
Number of pages5
JournalPsychiatry Research - Neuroimaging
Issue number2
Publication statusPublished - Feb 28 2011


  • Anterior limb of internal capsule
  • Diffusion tensor imaging
  • ErbB4
  • Magnetic resonance imaging
  • NRG1
  • Voxel based morphometry

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Radiology Nuclear Medicine and imaging
  • Neuroscience (miscellaneous)


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