title: A Neuregulin-1 schizophrenia susceptibility variant causes perihippocampal fiber tract anomalies in healthy young subjects.
abstract: BACKGROUND
  Changes in fiber tract architecture have gained attention as a potentially important aspect of schizophrenia neuropathology. Although the exact pathogenesis of these abnormalities yet remains to be elucidated, a genetic component is highly likely. Neuregulin-1 (NRG1) is one of the best-validated schizophrenia susceptibility genes. We here report the impact of the Neuregulin-1 rs35753505 variant on white matter structure in healthy young individuals with no family history of psychosis.
  
  
  METHODS
  We compared fractional anisotropy in 54 subjects that were either homozygous for the risk C allele carriers (n = 31) for rs35753505 or homozygous for the T allele (n = 23) using diffusion tensor imaging with 3T. Tract-Based Spatial Statistics (TBSS), a method especially developed for diffusion data analysis, was used to improve white matter registration and to focus the statistical analysis to major fiber tracts.
  
  
  RESULTS
  Statistical analysis showed that homozygous risk C allele carriers featured elevated fractional anisotropy (FA) in the right perihippocampal region and the white matter proximate to the left area 4p as well as the right hemisphere of the cerebellum. We found three clusters of reduced FA values in homozygous C allele carriers: in the left superior parietal region, the right prefrontal white matter and in the deep white matter of the left frontal lobe.
  
  
  CONCLUSIONS
  Our results highlight the importance of Neuregulin-1 for structural connectivity of the right medial temporal lobe. This finding is in line with well known neuropathological findings in this region in patients with schizophrenia.
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University Aachen, Germany ; Juelich Aachen Research Alliance - Translational Brain Medicine Juelich/Aachen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Nickl-Jockschat
authors.affiliation: Juelich Aachen Research Alliance - Translational Brain Medicine Juelich/Aachen, Germany ; Institute of Neurosciences and Medicine-4, Juelich Research Center Juelich, Germany.
authors.forename: Tony
authors.initials: T
authors.lastname: Stöcker
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Marburg Marburg, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Krug
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University Aachen, Germany.
authors.forename: Valentin
authors.initials: V
authors.lastname: Markov
authors.affiliation: Juelich Aachen Research Alliance - Translational Brain Medicine Juelich/Aachen, Germany ; Institute of Neurosciences and Medicine-4, Juelich Research Center Juelich, Germany.
authors.forename: Ruiwang
authors.initials: R
authors.lastname: Huang
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University Aachen, Germany ; Juelich Aachen Research Alliance - Translational Brain Medicine Juelich/Aachen, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Schneider
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University Aachen, Germany ; Juelich Aachen Research Alliance - Translational Brain Medicine Juelich/Aachen, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Habel
authors.affiliation: Institute of Clinical Neuroscience and Medical Psychology, Heinrich Heine University Düsseldorf, Germany ; Department of Neuroscience und Medicine, INM-1, Research Center Jülich Jülich, Germany.
authors.forename: Simon B
authors.initials: SB
authors.lastname: Eickhoff
authors.affiliation: Institute of Human Genetics, RWTH Aachen University Aachen, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Zerres
authors.affiliation: Department of Genomics, Life and Brain Center, University of Bonn Bonn, Germany.
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.affiliation: Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health Mannheim, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Treutlein
authors.affiliation: Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health Mannheim, Germany.
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.affiliation: Juelich Aachen Research Alliance - Translational Brain Medicine Juelich/Aachen, Germany ; Institute of Neurosciences and Medicine-4, Juelich Research Center Juelich, Germany ; Department of Neurology, RWTH Aachen University Aachen, Germany.
authors.forename: Nadim Jon
authors.initials: NJ
authors.lastname: Shah
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Marburg Marburg, Germany.
authors.forename: Tilo
authors.initials: T
authors.lastname: Kircher
mesh_terms: D000328:Adult; D002531:Cerebellum / Q000473:pathology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D020890:Neuregulin-1 / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology*; D066127:White Matter / Q000473:pathology*; D055815:Young Adult
chemical_list: D020890:Neuregulin-1
keywords: Anatomic connectivity; DTI; MRI; Neuregulin-1; brain; gene; hippocampus