title: Long acting injection versus oral risperidone in first-episode schizophrenia: differential impact on white matter myelination trajectory.
abstract: BACKGROUND
  Imaging and post-mortem studies provide converging evidence that subjects with schizophrenia (SZ) have a dysregulated trajectory of frontal lobe myelination. Prior MRI studies suggested that early in treatment of SZ, antipsychotic medications initially increase frontal lobe white matter (WM) volume, which subsequently declines prematurely in chronic stages of the disease. Insofar as the trajectory of WM decline associated with chronic disease may be due to medication non-adherence, it may be modifiable by long acting injection (LAI) formulations.
  
  
  OBJECTIVE
  Examine the impact of antipsychotic formulation on the myelination trajectory during a randomized six-month trial of LAI risperidone (RLAI) versus oral risperidone (RisO) in first-episode SZ subjects.
  
  
  METHODS
  Two groups of SZ subjects (RLAI, N=11; and RisO, N=13) that were matched in pre-randomization oral medication exposure and 14 healthy controls (HCs) were prospectively examined. Frontal lobe WM volume was estimated using inversion recovery (IR) MRI images. A brief neuropsychological battery that focused on reaction times was performed at the end of the study.
  
  
  METHODS
  WM volume change scores.
  
  
  RESULTS
  WM volume remained stable in the RLAI and decreased significantly in the RisO groups resulting in a significant differential treatment effect, while the HC had a WM change intermediate and not significantly different from the two SZ groups. WM increase was associated with faster reaction times in tests involving frontal lobe function.
  
  
  CONCLUSIONS
  The results suggest that RLAI may improve the trajectory of myelination in first-episode patients and have a beneficial impact on cognitive performance. Better adherence provided by LAI may underlie the modified trajectory of myelin development. In vivo MRI biomarkers of myelination can help clarify mechanisms of action of treatment interventions.
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, The David Geffen School of Medicine at UCLA, Los Angeles, California, United States. gbar@ucla.edu
authors.forename: George
authors.initials: G
authors.lastname: Bartzokis
authors.forename: Po H
authors.initials: PH
authors.lastname: Lu
authors.forename: Chetan P
authors.initials: CP
authors.lastname: Amar
authors.forename: Erika P
authors.initials: EP
authors.lastname: Raven
authors.forename: Nicole R
authors.initials: NR
authors.lastname: Detore
authors.forename: Lori L
authors.initials: LL
authors.lastname: Altshuler
authors.forename: Jim
authors.initials: J
authors.lastname: Mintz
authors.forename: Joseph
authors.initials: J
authors.lastname: Ventura
authors.forename: Laurie R
authors.initials: LR
authors.lastname: Casaus
authors.forename: John S
authors.initials: JS
authors.lastname: Luo
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Subotnik
authors.forename: Keith H
authors.initials: KH
authors.lastname: Nuechterlein
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D005625:Frontal Lobe / Q000187:drug effects / Q000473:pathology; D006801:Humans; D007267:Injections / Q000379:methods*; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000187:drug effects*; D011569:Psychiatric Status Rating Scales; D018967:Risperidone / Q000008:administration & dosage*; D012559:Schizophrenia / Q000188:drug therapy / Q000473:pathology*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D018967:Risperidone