title: Genetic variants in the ErbB4 gene are associated with white matter integrity.
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.
authors.affiliation: Inter-University Centre for Behavioural Neurosciences, University of Udine, Udine, Italy. riccardozuliani@googlemail.com
authors.forename: Riccardo
authors.initials: R
authors.lastname: Zuliani
authors.forename: T William J
authors.initials: TW
authors.lastname: Moorhead
authors.forename: Mark E
authors.initials: ME
authors.lastname: Bastin
authors.forename: Eve C
authors.initials: EC
authors.lastname: Johnstone
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Lawrie
authors.forename: Paolo
authors.initials: P
authors.lastname: Brambilla
authors.forename: Michael C
authors.initials: MC
authors.lastname: O'Donovan
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owen
authors.forename: Jeremy
authors.initials: J
authors.lastname: Hall
authors.forename: Andrew M
authors.initials: AM
authors.lastname: McIntosh
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D016880:Anisotropy; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D007839:Functional Laterality; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D020772:Internal Capsule / Q000033:anatomy & histology* / Q000378:metabolism; D008297:Male; D008568:Memory / Q000502:physiology; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000378:metabolism; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D066247:Receptor, ErbB-4
chemical_list: C587689:ERBB4 protein, human; D066246:ErbB Receptors; D066247:Receptor, ErbB-4