目标:家族性,产科,精神分裂症谱系障碍(SSD)的早期环境风险会改变正常的大脑发育,导致在症状发作之前形成特征性的脑缺陷模式。我们假设这些风险的潜在影响可能会增加青春期前儿童大脑与成人SSD缺陷模式的相似性。
方法:我们使用了青少年大脑和认知发育研究收集的数据(ABCD;N=8,940,年龄=9.9±0.1岁,4,633/4,307M/F),包括N=727(年龄=9.9±0.1岁,376/351M/F)有SSD家族史的儿童,为了评估祖先SSD病史对大脑的不利影响,产前和围产期环境,和消极的早期生活环境。我们使用区域脆弱性指数(RVI)来衡量儿童大脑模式与成人SSD模式的一致性,该模式来自对病例对照差异的大型荟萃分析。
结果:在有SSD家族史的儿童中,与传统的全脑和区域脑测量相比,RVI在祖先病史中捕获的差异明显更大。在有和没有SSD家族史的儿童中,与传统的大脑测量相比,RVI还捕获了与负面的产前和围产期环境以及早期生活经历相关的更多差异。
结论:总之,在大多数儿童不会发展SSD的队列中,家族性,产前和围产期,早期发育风险可以改变成年SSD患者的大脑模式。与成人SSD模式的个体相似性可以提供在精神病或前驱症状发作之前遗传和发育风险对大脑影响的早期生物标志物。
Familial, obstetric, and early-life environmental risks for schizophrenia spectrum disorder (SSD) alter normal cerebral development, leading to the formation of characteristic brain deficit patterns prior to onset of symptoms. We hypothesized that the insidious effects of these risks may increase brain similarity to adult SSD deficit patterns in prepubescent children.
We used data collected by the Adolescent Brain Cognitive Development (ABCD) Study (N = 8940, age = 9.9 ± 0.1 years, 4307/4633 female/male), including 727 (age = 9.9 ± 0.1 years, 351/376 female/male) children with family history of SSD, to evaluate unfavorable cerebral effects of ancestral SSD history, pre/perinatal environment, and negative early-life environment. We used a regional vulnerability index to measure the alignment of a child\'s cerebral patterns with the adult SSD pattern derived from a large meta-analysis of case-control differences.
In children with a family history of SSD, the regional vulnerability index captured significantly more variance in ancestral history than traditional whole-brain and regional brain measurements. In children with and without family history of SSD, the regional vulnerability index also captured more variance associated with negative pre/perinatal environment and early-life experiences than traditional brain measurements.
In summary, in a cohort in which most children will not develop SSD, familial, pre/perinatal, and early developmental risks can alter brain patterns in the direction observed in adult patients with SSD. Individual similarity to adult SSD patterns may provide an early biomarker of the effects of genetic and developmental risks on the brain prior to psychotic or prodromal symptom onset.