title: Localized differences in caudate and hippocampal shape are associated with schizophrenia but not antipsychotic type.
abstract: Caudate and hippocampal volume differences in patients with schizophrenia are associated with disease and antipsychotic treatment, but local shape alterations have not been thoroughly examined. Schizophrenia patients randomly assigned to haloperidol and olanzapine treatment underwent magnetic resonance imaging (MRI) at 3, 6, and 12 months. The caudate and hippocampus were represented as medial representations (M-reps); mesh structures derived from automatic segmentations of high resolution MRIs. Two quantitative shape measures were examined: local width and local deformation. A novel nonparametric statistical method, adjusted exponentially tilted (ET) likelihood, was used to compare the shape measures across the three groups while controlling for covariates. Longitudinal shape change was not observed in the hippocampus or caudate when the treatment groups and controls were examined in a global analysis, nor when the three groups were examined individually. Both baseline and repeated measures analysis showed differences in local caudate and hippocampal size between patients and controls, while no consistent differences were shown between treatment groups. Regionally specific differences in local hippocampal and caudate shape are present in schizophrenic patients. Treatment-related related longitudinal shape change was not observed within the studied timeframe. Our results provide additional evidence for disrupted cortico-basal ganglia-thalamo-cortical circuits in schizophrenia.
  
  
  BACKGROUND
  This longitudinal study was conducted from March 1, 1997 to July 31, 2001 at 14 academic medical centers (11 in the United States, one in Canada, one in the Netherlands, and one in England). This study was performed prior to the establishment of centralized registries of federally and privately supported clinical trials.
authors.affiliation: Department of Psychiatry, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Robert K
authors.initials: RK
authors.lastname: McClure
authors.forename: Martin
authors.initials: M
authors.lastname: Styner
authors.forename: Eric
authors.initials: E
authors.lastname: Maltbie
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Lieberman
authors.forename: Sylvain
authors.initials: S
authors.lastname: Gouttard
authors.forename: Guido
authors.initials: G
authors.lastname: Gerig
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Shi
authors.forename: Hongtu
authors.initials: H
authors.lastname: Zhu
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000494:pharmacology / Q000627:therapeutic use*; D002421:Caudate Nucleus / Q000187:drug effects / Q000473:pathology*; D004311:Double-Blind Method; D005260:Female; D006220:Haloperidol / Q000494:pharmacology / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D000077152:Olanzapine; D009929:Organ Size / Q000187:drug effects; D012559:Schizophrenia / Q000188:drug therapy / Q000473:pathology*
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D006220:Haloperidol; D000077152:Olanzapine