Impact on intracortical myelination trajectory of long acting injection versus oral risperidone in first-episode schizophrenia

SCHIZOPHRENIA RESEARCH

卷:140

Article

Bartzokis, George^1,2,3  Raven, Erika P.^1,3  Amar, Chetan P.^1,3  Detore, Nicole R.¹  Couvrette, Alexander J.^1,3  Mintz, Jim⁴  Ventura, Joseph¹  Casaus, Laurie R.¹  Luo, John S.¹  Subotnik, Kenneth L.¹  Nuechterlein, Keith H.^1,5 

[1] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, David Geffen Sch Med, Div Brain Mapping, Dept Neurol,Lab Neuroimaging, Los Angeles, CA 90095 USA

[3] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA

[4] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA

[5] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA

关键词: Antipsychotic;    Medication;    Dopamine;    Second generation;    Atypical;    Myelin;    White matter;    Gray matter;    Oligodendrocyte;    Development;    Aging;   

DOI  :  10.1016/j.schres.2012.06.036

来源: Elsevier

【 摘 要 】

Context: 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. Objectives: 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. Design: 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. Main outcome measure: 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. (C) 2012 Elsevier B. V. All rights reserved.

【 授权许可】

Free