Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Imaging Genetics Center, Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of USC, Los Angeles, California, USA.
Hum Brain Mapp. 2022 Nov;43(16):4970-4983. doi: 10.1002/hbm.26056. Epub 2022 Aug 30.
Severe mental illnesses (SMI), including major depressive (MDD), bipolar (BD), and schizophrenia spectrum (SSD) disorders have multifactorial risk factors and capturing their complex etiopathophysiology in an individual remains challenging. Regional vulnerability index (RVI) was used to measure individual's brain-wide similarity to the expected SMI patterns derived from meta-analytical studies. It is analogous to polygenic risk scores (PRS) that measure individual's similarity to genome-wide patterns in SMI. We hypothesized that RVI is an intermediary phenotype between genome and symptoms and is sensitive to both genetic and environmental risks for SMI. UK Biobank sample of N = 17,053/19,265 M/F (age = 64.8 ± 7.4 years) and an independent sample of SSD patients and controls (N = 115/111 M/F, age = 35.2 ± 13.4) were used to test this hypothesis. UKBB participants with MDD had significantly higher RVI-MDD (Cohen's d = 0.20, p = 1 × 10 ) and PRS-MDD (d = 0.17, p = 1 × 10 ) than nonpsychiatric controls. UKBB participants with BD and SSD showed significant elevation in the respective RVIs (d = 0.65 and 0.60; p = 3 × 10 and .009, respectively) and PRS (d = 0.57 and 1.34; p = .002 and .002, respectively). Elevated RVI-SSD were replicated in an independent sample (d = 0.53, p = 5 × 10 ). RVI-MDD and RVI-SSD but not RVI-BD were associated with childhood adversity (p < .01). In nonpsychiatric controls, elevation in RVI and PRS were associated with lower cognitive performance (p < 10 ) in six out of seven domains and showed specificity with disorder-associated deficits. In summary, the RVI is a novel brain index for SMI and shows similar or better specificity for SMI than PRS, and together they may complement each other in the efforts to characterize the genomic to brain level risks for SMI.
严重精神疾病（SMI），包括重性抑郁障碍（MDD）、双相障碍（BD）和精神分裂谱系障碍（SSD），具有多因素风险因素，个体的复杂病因生理学仍然具有挑战性。区域易损性指数（RVI）用于测量个体与从元分析研究中得出的预期 SMI 模式的大脑整体相似性。它类似于多基因风险评分（PRS），用于测量个体与 SMI 全基因组模式的相似性。我们假设 RVI 是基因组和症状之间的中间表型，并且对 SMI 的遗传和环境风险均敏感。使用 UK Biobank 样本 N = 17053/19265（男/女，年龄 = 64.8 ± 7.4 岁）和 SSD 患者和对照组的独立样本（N = 115/111，男/女，年龄 = 35.2 ± 13.4）来检验这一假设。与非精神病对照组相比，MDD 的 UKBB 参与者的 RVI-MDD（Cohen's d = 0.20，p = 1×10）和 PRS-MDD（d = 0.17，p = 1×10）显著升高。BD 和 SSD 的 UKBB 参与者的相应 RVI（d = 0.65 和 0.60；p = 3×10 和.009，分别）和 PRS（d = 0.57 和 1.34；p =.002 和.002，分别）显著升高。在独立样本中复制了升高的 RVI-SSD（d = 0.53，p = 5×10）。RVI-MDD 和 RVI-SSD，但不是 RVI-BD，与儿童期逆境有关（p<.01）。在非精神病对照组中，RVI 和 PRS 的升高与六个认知领域中的七个领域的认知表现下降有关（p<.01），并且与与障碍相关的缺陷具有特异性。总之，RVI 是 SMI 的一种新的大脑指标，其对 SMI 的特异性与 PRS 相似或更好，并且它们可以相互补充，以努力描述 SMI 的基因组到大脑水平的风险。
