Long acting injection versus oral risperidone in first-episode schizophrenia: Differential impact on white matter myelination trajectory

SCHIZOPHRENIA RESEARCH

卷:132

Article

Bartzokis, George^1,2,3  Lu, Po H.⁴  Amar, Chetan P.^1,3  Raven, Erika P.¹  Detore, Nicole R.¹  Altshuler, Lori L.¹  Mintz, Jim⁵  Ventura, Joseph¹  Casaus, Laurie R.¹  Luo, John S.¹  Subotnik, Kenneth L.¹  Nuechterlein, Keith H.^1,6 

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

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

[6] 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.2011.06.029

来源: Elsevier

【 摘 要 】

Context: 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. Objectives: 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. Design: 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. Main outcome measure: 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. Published by Elsevier B.V.

【 授权许可】

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