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.
Schizophr Res. 2012 Sep;140(1-3):122-8. doi: 10.1016/j.schres.2012.06.036. Epub 2012 Jul 17.
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.
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.
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.
ICM volume change scores were adjusted for the change in the HCs.
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).
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.
影像学和尸检研究表明，精神分裂症（SZ）患者额皮质内髓鞘形成失调。先前的 MRI 研究表明，在 SZ 的治疗早期，抗精神病药物最初会增加额皮质内髓鞘（ICM）体积，而在疾病的慢性阶段，这种体积会过早地下降。由于慢性 SZ 中 ICM 下降的轨迹是由于药物不依从或药代动力学原因引起的，因此它可能可以通过长效注射（LAI）制剂进行修饰。
在首发 SZ 患者的 LAI（RLAI）与口服（RisO）的六个月随机试验中，评估利培酮制剂对 ICM 轨迹的影响。
两组 SZ 患者（RLAI，N=9；RisO，N=13）按预先随机化的口服药物暴露情况进行匹配，前瞻性地在基线和 6 个月后进行检查，同时还检查了 12 名健康对照者（HCs）。使用反转恢复（IR）和质子密度（PD）MRI 图像评估额皮质 ICM 体积。跟踪药物依从性。
ICM 体积变化评分根据 HCs 的变化进行调整。
RLAI 组的 ICM 体积显著增加（p=.005），RisO 组的 ICM 体积增加不显著（p=.39），与健康对照组相比。组间治疗效果存在差异，但处于趋势水平（p=.093）。接受 RLAI 的 SZ 患者的药物依从性更好，ICM 增加更多（卡方 p<.05）。
结果表明，RLAI 可能会促进首发 SZ 患者的 ICM 发育。LAI 提供的更好的依从性和/或药代动力学可能会改变 ICM 轨迹。体内 MRI 髓鞘测量可以帮助阐明药物治疗作用的机制。
