title: Extensive gray matter volume reduction in treatment-resistant schizophrenia.
abstract: BACKGROUND
  Approximately one-third of people with schizophrenia are treatment-resistant and some do not achieve remission with clozapine, the gold-standard antipsychotic medication for treatment-resistant schizophrenia. This study compared global and regional brain volumes between treatment-respondent and treatment-resistant patients with schizophrenia, including a group of patients who were clozapine-resistant.
  
  
  METHODS
  T1-weighted brain MRIs were obtained on a 3T scanner in 20 controls and 52 people with schizophrenia who were selected based on their symptomatic responses to antipsychotic medication: 18 responded well to first-line atypical antipsychotics (FLR), 19 were treatment-resistant but responsive to clozapine monotherapy (TR), and 15 were ultra-treatment-resistant and did not respond to clozapine (UTR). Treatment groups were matched for disease duration and current psychopathology. SIENAX and FSL-VBM were used to investigate differences in the global brain, gray matter (GM), white matter, ventricular cerebrospinal fluid volumes, and regional GM volumes.
  
  
  RESULTS
  GM volume was significantly reduced in the TR and UTR groups compared with controls and the FLR group (p < 0.05). GM volume was significantly reduced in TR patients compared with FLRs in the superior, middle, and inferior temporal gyri, pre- and post-central gyri, middle and superior frontal gyri, right supramarginal gyrus, and right lateral occipital cortex. UTR patients showed reduced GM compared with FLRs in their right parietal operculum and left cerebellum. No significant volume differences were observed between TR and UTR groups.
  
  
  CONCLUSIONS
  These differences are unlikely to be solely due to medication effects, and reduced GM volume in treatment-resistant schizophrenia may represent an accelerated disease course or a different underlying pathology.
authors.affiliation: School of Pharmacy, University of Auckland, Auckland, New Zealand (Drs Anderson, Goldstein, and Russell); Centre for Brain Research, University of Auckland, Auckland, New Zealand (Drs Anderson, Goldstein, Kydd, and Russell); Department of Psychological Medicine, University of Auckland, Auckland, New Zealand (Dr Kydd).
authors.forename: Valerie M
authors.initials: VM
authors.lastname: Anderson
authors.affiliation: School of Pharmacy, University of Auckland, Auckland, New Zealand (Drs Anderson, Goldstein, and Russell); Centre for Brain Research, University of Auckland, Auckland, New Zealand (Drs Anderson, Goldstein, Kydd, and Russell); Department of Psychological Medicine, University of Auckland, Auckland, New Zealand (Dr Kydd).
authors.forename: Meghan E
authors.initials: ME
authors.lastname: Goldstein
authors.affiliation: School of Pharmacy, University of Auckland, Auckland, New Zealand (Drs Anderson, Goldstein, and Russell); Centre for Brain Research, University of Auckland, Auckland, New Zealand (Drs Anderson, Goldstein, Kydd, and Russell); Department of Psychological Medicine, University of Auckland, Auckland, New Zealand (Dr Kydd).
authors.forename: Robert R
authors.initials: RR
authors.lastname: Kydd
authors.affiliation: School of Pharmacy, University of Auckland, Auckland, New Zealand (Drs Anderson, Goldstein, and Russell); Centre for Brain Research, University of Auckland, Auckland, New Zealand (Drs Anderson, Goldstein, Kydd, and Russell); Department of Psychological Medicine, University of Auckland, Auckland, New Zealand (Dr Kydd). b.russell@auckland.ac.nz.
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Russell
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001921:Brain / Q000473:pathology; D016022:Case-Control Studies; D003024:Clozapine / Q000008:administration & dosage / Q000627:therapeutic use*; D004351:Drug Resistance; D005260:Female; D066128:Gray Matter / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D012559:Schizophrenia / Q000188:drug therapy* / Q000473:pathology*; D016896:Treatment Outcome; D066127:White Matter / Q000473:pathology; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine
keywords: MRI; clozapine; treatment-resistant schizophrenia; voxel-based morphometry