Abstract

Schizophrenia (SCZ) is associated with structural brain changes, with considerable variation in the extent to which these cortical regions are influenced. We present a novel metric that summarises individual structural variation across the brain, while considering prior effect sizes, established via meta-analysis. We determine individual participant deviation from a within-sample-norm across structural MRI regions of interest (ROIs). For each participant, we weight the normalised deviation of each ROI by the effect size (Cohen’s d) of the difference between SCZ/control for the corresponding ROI from the SCZ Enhancing Neuroimaging Genomics through Meta-Analysis working group. We generate a morphometric risk score (MRS) representing the average of these weighted deviations. We investigate if SCZ-MRS is elevated in a SCZ case/control sample (N_CASE = 50; N_CONTROL = 125), a replication sample (N_CASE = 23; N_CONTROL = 20) and a sample of asymptomatic young adults with extreme SCZ polygenic risk (N_HIGH-SCZ-PRS = 95; N_LOW-SCZ-PRS = 94). SCZ cases had higher SCZ-MRS than healthy controls in both samples (Study 1: β = 0.62, P < 0.001; Study 2: β = 0.81, P = 0.018). The high liability SCZ-PRS group also had a higher SCZ-MRS (Study 3: β = 0.29, P = 0.044). Furthermore, the SCZ-MRS was uniquely associated with SCZ status, but not attention-deficit hyperactivity disorder (ADHD), whereas an ADHD-MRS was linked to ADHD status, but not SCZ. This approach provides a promising solution when considering individual heterogeneity in SCZ-related brain alterations by identifying individual’s patterns of structural brain-wide alterations.

中文翻译：

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使用精神分裂症 Meta 分析先验的结构 MRI 的形态学分析在两个独立样本和具有高多基因风险的个体样本中区分患者和对照

摘要

精神分裂症 (SCZ) 与大脑结构变化相关，这些皮层区域受到影响的程度存在相当大的差异。我们提出了一种新的指标，它总结了大脑中的个体结构变化，同时考虑了通过荟萃分析建立的先验效应大小。我们确定个体参与者偏离结​​构 MRI 感兴趣区域 (ROI) 的样本内规范。对于每个参与者，我们通过效果大小（Cohen's d) SCZ/control 与 SCZ 通过元分析工作组增强神经影像基因组学的相应 ROI 之间的差异。我们生成代表这些加权偏差平均值的形态风险评分 (MRS)。我们调查 SCZ-MRS 是否在 SCZ 病例/对照样本（N _CASE = 50；N _CONTROL = 125）、复制样本（N _CASE = 23；N _CONTROL = 20）和无症状的年轻人样本中升高SCZ 多基因风险（N _HIGH-SCZ-PRS = 95；N _LOW-SCZ-PRS = 94）。在两个样本中，SCZ 病例的 SCZ-MRS 均高于健康对照（研究 1：β= 0.62，P < 0.001；研究 2：β = 0.81，P = 0.018）。高负债 SCZ-PRS 组也有较高的 SCZ-MRS（研究 3：β = 0.29，P = 0.044）。此外，SCZ-MRS 与 SCZ 状态唯一相关，但与注意力缺陷多动障碍 (ADHD) 无关，而 ADHD-MRS 与 ADHD 状态相关，但与 SCZ 无关。当通过识别个体的全脑结构改变模式来考虑 SCZ 相关大脑改变中的个体异质性时，这种方法提供了一个有前途的解决方案。