Tishler T A, Ellingson B M, Salvadore G, Baker P, Turkoz I, Subotnik K L, de la Fuente-Sandoval C, Nuechterlein K H, Alphs L
Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA; UCLA Center for Computer Vision and Imaging Biomarkers, Departments of Radiological Sciences and Psychiatry, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, USA.
Schizophr Res. 2023 May;255:195-202. doi: 10.1016/j.schres.2023.03.023. Epub 2023 Mar 31.
We investigated changes in brain intracortical myelin (ICM) volume in the frontal lobe after 9 months of treatment with paliperidone palmitate (PP) compared with 9 months of treatment with oral antipsychotics (OAP) in participants with recent-onset schizophrenia or schizophreniform disorder from the Disease Recovery Evaluation and Modification (DREaM) study, a randomized, open-label, delayed-start trial.
DREaM included 3 phases: Part I, a 2-month oral run-in; Part II, a 9-month disease progression phase (PP or OAP); and Part III, 9 months of additional treatment (participants receiving PP continued PP [PP/PP] and participants receiving OAP were rerandomized to receive either PP [OAP/PP] or OAP [OAP/OAP]). In Part II, magnetic resonance imaging (MRI) and functional and symptomatic assessment was performed at baseline, day 92, and day 260. ICM volume as a fraction of the entire brain volume was quantified by subtraction of a proton density image from an inversion recovery image. Within-treatment-group changes from baseline were assessed by paired t-tests. Analysis of covariance was used to analyze ICM volume changes between treatment groups, adjusting for country.
The MRI analysis sample size included 71 DREaM participants (PP, 23; OAP, 48) and 64 healthy controls. At baseline, mean adjusted ICM fraction values did not differ between groups (PP, 0.057; OAP, 0.058, p = 0.79). By day 92, the adjusted ICM fraction in the OAP group had decreased significantly (change from baseline, -0.002; p = 0.001), whereas the adjusted ICM fraction remained unchanged from baseline in the PP group (0.000; p = 0.80). At day 260, the change from baseline in adjusted ICM fraction was -0.004 (p = 0.004) in the OAP group and -0.001 (p = 0.728) in the PP group. The difference between treatment groups did not reach statistical significance (p = 0.147).
In participants with recent-onset schizophrenia or schizophreniform disorder, frontal ICM volume was preserved at baseline levels in those treated with PP over 9 months. However, a decrease of frontal ICM volume was observed among participants treated with OAPs.
clinicaltrials.gov identifier NCT02431702.
在疾病康复评估与修正（DREaM）研究中，我们调查了棕榈酸帕利哌酮（PP）治疗9个月后与口服抗精神病药物（OAP）治疗9个月相比，近期发病的精神分裂症或精神分裂症样障碍参与者额叶皮质内髓鞘（ICM）体积的变化，该研究是一项随机、开放标签、延迟启动试验。
DREaM包括3个阶段：第一阶段，为期2个月的口服导入期；第二阶段，为期9个月的疾病进展期（PP或OAP）；第三阶段，额外9个月的治疗（接受PP治疗的参与者继续使用PP [PP/PP]，接受OAP治疗的参与者重新随机分组，接受PP [OAP/PP]或OAP [OAP/OAP]）。在第二阶段，在基线、第92天和第260天进行磁共振成像（MRI）以及功能和症状评估。通过从反转恢复图像中减去质子密度图像来量化ICM体积占整个脑体积的比例。通过配对t检验评估治疗组内与基线相比的变化。使用协方差分析来分析治疗组之间的ICM体积变化，并对国家进行校正。
MRI分析样本包括71名DREaM参与者（PP组23名；OAP组48名）和64名健康对照者。在基线时，各组间平均校正ICM比例值无差异（PP组为0.057；OAP组为0.058，p = 0.79）。到第92天，OAP组的校正ICM比例显著下降（与基线相比变化为-0.002；p = 0.001），而PP组的校正ICM比例与基线相比保持不变（0.000；p = 0.80）。在第260天，OAP组校正ICM比例与基线相比的变化为-0.004（p = 0.004），PP组为-0.001（p = 0.728）。治疗组之间的差异未达到统计学显著性（p = 0.147）。
在近期发病的精神分裂症或精神分裂症样障碍参与者中，接受PP治疗9个月的患者额叶ICM体积维持在基线水平。然而，接受OAP治疗的参与者中观察到额叶ICM体积减少。
clinicaltrials.gov标识符NCT02431702。
