title: Grey matter, an endophenotype for schizophrenia? A voxel-based morphometry study in siblings of patients with schizophrenia.
abstract: BACKGROUND
  Grey matter, both volume and concentration, has been proposed as an endophenotype for schizophrenia given a number of reports of grey matter abnormalities in relatives of patients with schizophrenia. However, previous studies on grey matter abnormalities in relatives have produced inconsistent results. The aim of the present study was to examine grey matter differences between controls and siblings of patients with schizophrenia and to examine whether the age, genetic loading or subclinical psychotic symptoms of selected individuals could explain the previously reported inconsistencies.
  
  
  METHODS
  We compared the grey matter volume and grey matter concentration of healthy siblings of patients with schizophrenia and healthy controls matched for age, sex and education using voxel-based morphometry (VBM). Furthermore, we selected subsamples based on age (< 30 yr), genetic loading and subclinical psychotic symptoms to examine whether this would lead to different results.
  
  
  RESULTS
  We included 89 siblings and 69 controls in our study. The results showed that siblings and controls did not differ significantly on grey matter volume or concentration. Furthermore, specifically selecting participants based on age, genetic loading or subclinical psychotic symptoms did not alter these findings.
  
  
  CONCLUSIONS
  The main limitation was that subdividing the sample resulted in smaller samples for the subanalyses. Furthermore, we used MRI data from 2 different scanner sites.
  
  
  CONCLUSIONS
  These results indicate that grey matter measured through VBM might not be a suitable endophenotype for schizophrenia.
authors.affiliation: Neuroimaging Center, University of Groningen, University Medical Center Groningen; Hanze University of Applied Sciences Groningen, Academy of Social studies, Groningen, The Netherlands.
authors.forename: Jorien
authors.initials: J
authors.lastname: van der Velde
authors.affiliation: Department of Educational Neuroscience, Faculty of Psychology and Education, VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Paula M
authors.initials: PM
authors.lastname: Gromann
authors.affiliation: Lentis, Center for Mental Healthcare, Groningen, The Netherlands.
authors.forename: Marte
authors.initials: M
authors.lastname: Swart
authors.affiliation: The Department of Psychiatry, Academic Medical Center Amsterdam, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Lieuwe
authors.initials: L
authors.lastname: de Haan
authors.affiliation: The Department of Neuroscience and Psychiatry, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Durk
authors.initials: D
authors.lastname: Wiersma
authors.affiliation: The Department of Neuroscience and Psychiatry, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Richard
authors.initials: R
authors.lastname: Bruggeman
authors.affiliation: The Department of Educational Neuroscience, Faculty of Psychology and Education, VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Lydia
authors.initials: L
authors.lastname: Krabbendam
authors.affiliation: The Neuroimaging Center, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: André
authors.initials: A
authors.lastname: Aleman
mesh_terms: D000328:Adult; D000375:Aging / Q000473:pathology; D001921:Brain / Q000473:pathology*; D058068:Endophenotypes; D005260:Female; D066128:Gray Matter / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009929:Organ Size; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000235:genetics / Q000473:pathology*; D035781:Siblings