title: Brain volume changes over the first year of treatment in schizophrenia: relationships to antipsychotic treatment.
abstract: BACKGROUND
  Progressive brain volume reductions have been described in schizophrenia, and an association with antipsychotic exposure has been reported.
  
  
  METHODS
  We compared percentage changes in grey and white matter volume from baseline to month 12 in 23 previously antipsychotic-naïve patients with a first episode of schizophrenia or schizophreniform disorder who were treated with the lowest effective dose of flupenthixol decanoate depot formulation, with 53 matched healthy individuals. Total antipsychotic dose was precisely calculated and its relationship with brain volume changes investigated. Relationships between volumetric changes and treatment were further investigated in terms of treatment response (changes in psychopathology and functionality) and treatment-related adverse-events (extrapyramidal symptoms and weight gain).
  
  
  RESULTS
  Excessive cortical volume reductions were observed in patients [-4.6 (6.6)%] v. controls [-1.12 (4.0)%] (p = 0.009), with no significant group differences for changes in subcortical grey matter and white matter volumes. In a multiple regression model, the only significant predictor of cortical volume change was total antipsychotic dose received (p = 0.04). Cortical volume change was not significantly associated with the changes in psychopathology, functionality, extrapyramidal symptoms and body mass index or age, gender and duration of untreated psychosis.
  
  
  CONCLUSIONS
  Brain volume reductions associated with antipsychotic treatment are not restricted to poor outcome patients and occur even with the lowest effective dose of antipsychotic. The lack of an association with poor treatment response or treatment-related adverse effects counts against cortical volume reductions reflecting neurotoxicity, at least in the short term. On the other hand, the volume reductions were not linked to the therapeutic benefits of antipsychotics.
authors.affiliation: Department of Psychiatry, Faculty of Medicine and Health Sciences,Stellenbosch University,Cape Town,South Africa.
authors.forename: R
authors.initials: R
authors.lastname: Emsley
authors.affiliation: Department of Psychiatry, Faculty of Medicine and Health Sciences,Stellenbosch University,Cape Town,South Africa.
authors.forename: L
authors.initials: L
authors.lastname: Asmal
authors.affiliation: Department of Psychiatry, Faculty of Medicine and Health Sciences,Stellenbosch University,Cape Town,South Africa.
authors.forename: S
authors.initials: S
authors.lastname: du Plessis
authors.affiliation: Department of Psychiatry, Faculty of Medicine and Health Sciences,Stellenbosch University,Cape Town,South Africa.
authors.forename: B
authors.initials: B
authors.lastname: Chiliza
authors.affiliation: Department of Psychiatry, Faculty of Medicine and Health Sciences,Stellenbosch University,Cape Town,South Africa.
authors.forename: L
authors.initials: L
authors.lastname: Phahladira
authors.affiliation: Department of Psychiatry, Faculty of Medicine and Health Sciences,Stellenbosch University,Cape Town,South Africa.
authors.forename: S
authors.initials: S
authors.lastname: Kilian
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D003692:Delayed-Action Preparations; D005260:Female; D005475:Flupenthixol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D011618:Psychotic Disorders / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology; D016896:Treatment Outcome; D066127:White Matter / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; C007761:flupenthixol decanoate; D005475:Flupenthixol
keywords: Brain-volume; antipsychotic; cortex-volume; dose-response; flupenthixol; schizophrenia