Impact on intracortical myelination trajectory of long acting injection versus oral risperidone in first-episode schizophrenia.
BACKGROUND
Imaging and post-mortem studies suggest that frontal lobe intracortical myelination is dysregulated in schizophrenia (SZ). Prior MRI studies suggested that early in the treatment of SZ, antipsychotic medications initially increase frontal lobe intracortical myelin (ICM) volume, which subsequently declines prematurely in chronic stages of the disease. Insofar as the trajectory of ICM decline in chronic SZ is due to medication non-adherence or pharmacokinetics, it may be modifiable by long acting injection (LAI) formulations.


OBJECTIVE
Assess the effect of risperidone formulation on the ICM trajectory during a six-month randomized trial of LAI (RLAI) versus oral (RisO) in first-episode SZ subjects.


METHODS
Two groups of SZ subjects (RLAI, N=9; and RisO, N=13) matched on pre-randomization oral medication exposure were prospectively examined at baseline and 6 months later, along with 12 healthy controls (HCs). Frontal lobe ICM volume was assessed using inversion recovery (IR) and proton density (PD) MRI images. Medication adherence was tracked.


METHODS
ICM volume change scores were adjusted for the change in the HCs.


RESULTS
ICM volume increased significantly (p=.005) in RLAI and non-significantly (p=.39) in the RisO groups compared with that of the healthy controls. A differential between-group treatment effect was at a trend level (p=.093). SZ subjects receiving RLAI had better medication adherence and more ICM increases (chi-square p<.05).


CONCLUSIONS
The results suggest that RLAI may promote ICM development in first-episode SZ patients. Better adherence and/or pharmacokinetics provided by LAI may modify the ICM trajectory. In vivo MRI myelination measures can help clarify pharmacotherapeutic mechanisms of action.
Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, The David Geffen School of Medicine at UCLA, Los Angeles, California, USA. gbar@ucla.edu
George
G
Bartzokis
Po H
PH
Lu
Erika P
EP
Raven
Chetan P
CP
Amar
Nicole R
NR
Detore
Alexander J
AJ
Couvrette
Jim
J
Mintz
Joseph
J
Ventura
Laurie R
LR
Casaus
John S
JS
Luo
Kenneth L
KL
Subotnik
Keith H
KH
Nuechterlein
D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D004333:Drug Administration Routes; D016503:Drug Delivery Systems; D005260:Female; D005500:Follow-Up Studies; D005625:Frontal Lobe / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D010349:Patient Compliance; D011569:Psychiatric Status Rating Scales; D018967:Risperidone / Q000008:administration & dosage*; D012559:Schizophrenia / Q000188:drug therapy* / Q000473:pathology*; D055815:Young Adult
D014150:Antipsychotic Agents; D018967:Risperidone