Extreme deviations from the normative model reveal cortical heterogeneity and associations with negative symptom severity in first-episode psychosis from the OPTiMiSE and GAP studies.
Extreme deviations from the normative model reveal cortical heterogeneity and associations with negative symptom severity in first-episode psychosis from the OPTiMiSE and GAP studies.
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优化和 GAP 研究显示，与规范模型的极端偏差揭示了皮质异质性以及与首发精神病中阴性症状严重程度的关联。
DOI：
10.1038/s41398-023-02661-6
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发表时间：
2023-12-02
影响因子：
6.8
通讯作者：
Marquand, Andre F.
中科院分区：
文献类型：
--
作者：
Worker, Amanda;Berthert, Pierre;Lawrence, Andrew J.;Kia, Seyed Mostafa;Arango, Celso;Dinga, Richard;Galderisi, Silvana;Glenthoj, Birte;Kahn, Rene S.;Leslie, Anoushka;Murray, Robin M.;Pariante, Carmine M.;Pantelis, Christos;Weiser, Mark;Winter-van Rossum, Inge;Mcguire, Philip;Dazzan, Paola;Marquand, Andre F.
目前还没有可量化的方法来预测首发精神病患者的长期临床结果。开发有用的标记物的一个主要障碍是生物异质性，在不同的个体中，许多不同的病理机制可能导致同一组症状。基于标准的健康人群范围，通过识别比预期更薄的皮质区域，标准建模已被用于量化已建立的精神障碍中的这种异质性。这些大脑的非典型性是在个体水平上测量的，因此在临床环境中可能有用。然而，目前还不清楚在第一次精神病发作时是否可以检测到个体大脑结构的变化，以及这些变化是否与随后的临床结果有关。我们将皮质厚度的标准模型应用于首发精神病患者的样本，目的是量化异质性，并使用任何皮质非典型模式来预测从基线到95周(中位数随访=4)的症状和对抗精神病药物的反应。使用Freesurfer V6.0.0处理来自GAP和优化样本的T1加权脑磁共振图像，得到148个皮质厚度特征。对现有的皮质厚度标准模型(n = 37,126)进行调整，以整合来自每个临床部位的数据，并考虑性别和部位的影响。我们的测试样本包括对照组(n = 14 9，平均年龄=2 6，SD = 6.7)和患者数据(n = 2 95，平均年龄=26，SD = 6.7)，这个样本被用来估计与标准模型的偏差，并随后进行统计分析。对于每个个体，148个皮质厚度特征被映射到正态分布的百分位数，并转换为反映与人群平均值的距离的z分数。单个皮质厚度指标与平均值的+/-2.6标准差被认为是与正常值的极端偏差。我们发现，不超过6.4%的精神病患者在单个大脑区域(区域重叠)出现极端偏差，显示出高度的异质性。对每个区域进行Mann-Whitney U检验，观察到FEP患者额叶、颞叶、顶叶和枕叶的z分数显著降低。最后，线性混合效应模型表明，基线时顶叶和颞叶皮质厚度的负偏差与中期内更严重的负面症状有关。这项研究表明，即使在症状出现的早期阶段，标准化建模也提供了一个框架，以确定可用于早期个性化干预和分层的个性化皮质标志物。
There is currently no quantifiable method to predict long-term clinical outcomes in patients presenting with a first episode of psychosis. A major barrier to developing useful markers for this is biological heterogeneity, where many different pathological mechanisms may underly the same set of symptoms in different individuals. Normative modelling has been used to quantify this heterogeneity in established psychotic disorders by identifying regions of the cortex which are thinner than expected based on a normative healthy population range. These brain atypicalities are measured at the individual level and therefore potentially useful in a clinical setting. However, it is still unclear whether alterations in individual brain structure can be detected at the time of the first psychotic episode, and whether they are associated with subsequent clinical outcomes. We applied normative modelling of cortical thickness to a sample of first-episode psychosis patients, with the aim of quantifying heterogeneity and to use any pattern of cortical atypicality to predict symptoms and response to antipsychotic medication at timepoints from baseline up to 95 weeks (median follow-ups = 4). T1-weighted brain magnetic resonance images from the GAP and OPTiMiSE samples were processed with Freesurfer V6.0.0 yielding 148 cortical thickness features. An existing normative model of cortical thickness (n = 37,126) was adapted to integrate data from each clinical site and account for effects of gender and site. Our test sample consisted of control participants (n = 149, mean age = 26, SD = 6.7) and patient data (n = 295, mean age = 26, SD = 6.7), this sample was used for estimating deviations from the normative model and subsequent statistical analysis. For each individual, the 148 cortical thickness features were mapped to centiles of the normative distribution and converted to z-scores reflecting the distance from the population mean. Individual cortical thickness metrics of +/– 2.6 standard deviations from the mean were considered extreme deviations from the norm. We found that no more than 6.4% of psychosis patients had extreme deviations in a single brain region (regional overlap) demonstrating a high degree of heterogeneity. Mann-Whitney U tests were run on z-scores for each region and significantly lower z-scores were observed in FEP patients in the frontal, temporal, parietal and occipital lobes. Finally, linear mixed-effects modelling showed that negative deviations in cortical thickness in parietal and temporal regions at baseline are related to more severe negative symptoms over the medium-term. This study shows that even at the early stage of symptom onset normative modelling provides a framework to identify individualised cortical markers which can be used for early personalised intervention and stratification.
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影响因子：
6.9
作者：
Vieira S;Gong Q;Scarpazza C;Lui S;Huang X;Crespo-Facorro B;Tordesillas-Gutierrez D;de la Foz VO;Setien-Suero E;Scheepers F;van Haren NEM;Kahn R;Reis Marques T;Ciufolini S;Di Forti M;Murray RM;David A;Dazzan P;McGuire P;Mechelli A
通讯作者：
Mechelli A
使用规范模型了解临床人群中的异质性：超越病例对照研究。
影响因子：
10.6
作者：
Marquand AF;Rezek I;Buitelaar J;Beckmann CF
通讯作者：
Beckmann CF
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
6.6
作者：
Di Forti, Marta;Sallis, Hannah;Murray, Robin M.
通讯作者：
Murray, Robin M.
影响因子：
4.5
作者：
Austin, Stephen F.;Mors, Ole;Nordentoft, Merete
通讯作者：
Nordentoft, Merete