Stein Center for Research on Aging, 9500 Gilman Drive, University of California San Diego, La Jolla, CA 92093-0664, USA.
Schizophr Res. 2013 Jan;143(1):90-6. doi: 10.1016/j.schres.2012.10.033. Epub 2012 Dec 5.
Heterogeneity in clinical outcomes may be caused by factors working at multiple levels, e.g., between groups, between subjects, or within subjects over time. A more nuanced assessment of differences in variation among schizophrenia patients and between patients and healthy comparison subjects can clarify etiology and even facilitate the identification of patient subtypes with common neuropathology and clinical course.
We compared trajectories (mean duration of 3.5years) of cognitive impairments in a sample of 201 community-dwelling schizophrenia (SCZ) patients (aged 40-100years) with 67 healthy comparison (HC) subjects. We employed growth mixture models to discover subclasses with more homogenous between-subject variation in cognitive trajectories. Post hoc analyses determined factors associated with class membership and class-specific correlates of cognitive trajectories.
Three latent classes were indicated: Class 1 (85% HC and 50% SCZ) exhibited relatively high and stable trajectories of cognition, Class 2 (15% HC and 40% SCZ) exhibited lower, modestly declining trajectories, and Class 3 (10% SCZ) exhibited lower, more rapidly declining trajectories. Within the patient group, membership in Classes 2-3 was associated with worse negative symptoms and living in a board and care facility.
These results bridge the gap between schizophrenia studies demonstrating cognitive decline and those demonstrating stability. Moreover, a finer-grained characterization of heterogeneity in cognitive trajectories has practical implications for interventions and for case management of patients who show accelerated cognitive decline. Such a characterization requires study designs and analyses sensitive to between- and within-patient heterogeneity in outcomes.
临床结果的异质性可能是由多个层次的因素引起的，例如组间、个体间或个体随时间的变化。更细致地评估精神分裂症患者之间以及患者与健康对照组之间变异的差异，可以阐明病因，甚至有助于识别具有共同神经病理学和临床病程的患者亚类。
我们比较了 201 名社区居住的精神分裂症（SCZ）患者（年龄 40-100 岁）和 67 名健康对照组（HC）受试者的认知障碍轨迹（平均持续时间为 3.5 年）。我们采用增长混合模型发现认知轨迹在个体间具有更同质的变化的亚类。事后分析确定了与类别成员相关的因素以及认知轨迹的类别特异性相关性。
表明存在三个潜在类别：类别 1（85%的 HC 和 50%的 SCZ）表现出相对较高且稳定的认知轨迹，类别 2（15%的 HC 和 40%的 SCZ）表现出较低、适度下降的轨迹，类别 3（10%的 SCZ）表现出较低、下降更快的轨迹。在患者组中，类别 2-3 的成员与更严重的阴性症状和居住在寄宿和护理设施有关。
这些结果弥合了精神分裂症研究中表明认知能力下降和稳定的研究之间的差距。此外，对认知轨迹异质性的更精细描述对干预措施和对表现出加速认知衰退的患者的病例管理具有实际意义。这种描述需要对结果的个体间和个体内异质性具有敏感性的研究设计和分析。
