title: Hippocampal shape abnormalities of patients with childhood-onset schizophrenia and their unaffected siblings.
abstract: OBJECTIVE
  The hippocampus has been implicated in the pathogenesis of schizophrenia, and hippocampal volume deficits have been a consistently reported abnormality, but the subregional specificity of the deficits remains unknown. The authors explored the nature and developmental trajectory of subregional shape abnormalities of the hippocampus in patients with childhood-onset schizophrenia (COS), their healthy siblings, and healthy volunteers.
  
  
  METHODS
  Two hundred twenty-five anatomic brain magnetic resonance images were obtained from 103 patients with COS, 169 from their 79 healthy siblings, and 255 from 101 age- and sex-matched healthy volunteers (age range = 9-29 years). The hippocampus was segmented using FreeSurfer automated image analysis software, and hippocampal shape was evaluated by comparing subjects at more than 6,000 vertices on the left and right hippocampal surfaces. Longitudinal data were examined using mixed model regression analysis.
  
  
  RESULTS
  Patients with COS showed significant bilateral inward deformation in the anterior hippocampus. Healthy siblings also showed a trend for anterior inward deformation. However, the trajectory of shape change did not differ significantly between the groups. Inward deformations in the anterior hippocampus were positively related to positive symptom severity, whereas outward surface displacement was positively related to overall functioning.
  
  
  CONCLUSIONS
  This is the first and largest longitudinal three-way analysis of subregional hippocampal shape abnormalities in patients with COS and their healthy siblings compared with healthy controls. The anterior hippocampal abnormalities in COS suggest the pathophysiologic importance of this subregion in schizophrenia. The trend level and overlapping shape abnormalities in the healthy siblings suggest a more subtle, subregionally specific neuroanatomic endophenotype.
authors.affiliation: Child Psychiatry Branch of the National Institute of Mental Health, Bethesda, MD 20892, USA. sarahmetthe@gmail.com
authors.forename: Sarah L M
authors.initials: SL
authors.lastname: Johnson
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Kathryn I
authors.initials: KI
authors.lastname: Alpert
authors.forename: Deanna
authors.initials: D
authors.lastname: Greenstein
authors.forename: Liv
authors.initials: L
authors.lastname: Clasen
authors.forename: Francois
authors.initials: F
authors.lastname: Lalonde
authors.forename: Rachel
authors.initials: R
authors.lastname: Miller
authors.forename: Judith
authors.initials: J
authors.lastname: Rapoport
authors.forename: Nitin
authors.initials: N
authors.lastname: Gogtay
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D005260:Female; D006624:Hippocampus / Q000002:abnormalities / Q000033:anatomy & histology / Q000473:pathology*; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D012561:Schizophrenia, Childhood / Q000473:pathology*; D035781:Siblings; D055815:Young Adult