Background Clinical forecasting models have potential to optimize treatment and improve outcomes in psychosis, but predicting long-term outcomes is challenging and long-term follow-up data are scarce. In this 10-year longitudinal study, we aimed to characterize the temporal evolution of cortical correlates of psychosis and their associations with symptoms. Design Structural magnetic resonance imaging (MRI) from people with first-episode psychosis and controls (n = 79 and 218) were obtained at enrollment, after 12 months (n = 67 and 197), and 10 years (n = 23 and 77), within the Thematically Organized Psychosis (TOP) study. Normative models for cortical thickness estimated on public MRI datasets (n = 42 983) were applied to TOP data to obtain deviation scores for each region and timepoint. Positive and Negative Syndrome Scale (PANSS) scores were acquired at each timepoint along with registry data. Linear mixed effects models assessed effects of diagnosis, time, and their interactions on cortical deviations plus associations with symptoms. Results LMEs revealed conditional main effects of diagnosis and time × diagnosis interactions in a distributed cortical network, where negative deviations in patients attenuate over time. In patients, symptoms also attenuate over time. LMEs revealed effects of anterior cingulate on PANSS total, and insular and orbitofrontal regions on PANSS negative scores. Conclusions This long-term longitudinal study revealed a distributed pattern of cortical differences which attenuated over time together with a reduction in symptoms. These findings are not in line with a simple neurodegenerative account of schizophrenia, and deviations from normative models offer a promising avenue to develop biomarkers to track clinical trajectories over time.

中文翻译：

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使用规范模型对首发精神病患者脑皮质厚度进行 10 年纵向研究


背景 临床预测模型有潜力优化精神病的治疗和改善结果，但预测长期结果具有挑战性，而且长期随访数据稀缺。在这项为期 10 年的纵向研究中，我们旨在描述精神病皮质相关因素的时间演变及其与症状的关联。设计 在入组时、12 个月后（n = 67 和 197）以及 10 年后（n = 23 和 77）获得首发精神病患者和对照者（n = 79 和 218）的结构磁共振成像 (MRI)。 ，在主题组织精神病（TOP）研究中。将公共 MRI 数据集 (n = 42 983) 估计的皮质厚度规范模型应用于 TOP 数据，以获得每个区域和时间点的偏差分数。在每个时间点获取阳性和阴性症状量表（PANSS）评分以及登记数据。线性混合效应模型评估了诊断、时间及其相互作用对皮质偏差以及与症状的关联的影响。结果 LME 揭示了分布式皮质网络中诊断和时间×诊断相互作用的条件主效应，其中患者的负偏差随着时间的推移而减弱。对于患者来说，症状也会随着时间的推移而减弱。 LME 揭示了前扣带回对 PANSS 总分的影响，以及岛叶和眶额区域对 PANSS 负分的影响。结论 这项长期纵向研究揭示了皮质差异的分布模式，这种差异随着时间的推移而减弱，症状也随之减轻。这些发现与精神分裂症的简单神经退行性解释不一致，并且与规范模型的偏差为开发生物标记物以跟踪随时间推移的临床轨迹提供了一条有希望的途径。