Neurodevelopmental dimensional assessment of young children at high genomic risk of neuropsychiatric conditions.
Neurodevelopmental dimensional assessment of young children at high genomic risk of neuropsychiatric conditions.
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22q11.2缺失的个体患神经发育和精神疾病的风险显著增加。很少有研究调查这种风险如何在幼儿期表现出来，以及哪些因素可能导致发育变异。深入了解这一点可以阐明风险的跨诊断标志物，这些标志物可能是神经精神结局后期发展的基础。32名22q11.2缺失综合征（22q11.2DS）患儿（平均年龄= 4.1 [SD = 1.2]岁）和12名同胞对照（平均年龄= 4.1 [SD = 1.5]岁）在几个发育领域进行了深入的维度表型分析，这些发育领域被选为神经发育和精神病倾向的潜在早期指标。比较22q11.2DS和同胞对照的尺寸发育表型。对于自闭症特征，父母和孩子都使用社会反应量表进行表型分析。22q11.2DS的幼儿在一系列发育领域相对于兄弟姐妹对照表现出较大的损伤（Hedge g ≥ 0.8），以及高的跨诊断神经发育和精神病学特征。聚类分析揭示了一个22q11.2DS儿童亚组（n = 16; 53%），其中神经发育和精神病倾向特别增加，与其他22q11.2DS儿童和非携带者兄弟姐妹不同。探索性分析表明，早期运动和睡眠障碍指数的神经发育和精神疾病的后果。母亲的孤独症特征评分可预测22q11.2DS患儿的孤独症特征（组内相关系数= 0.47，p = 0.046，n = 31）。虽然精神疾病通常出现在22q11.2DS的青春期和成年期，但我们的探索性研究能够确定一系列早期风险指标。此外，研究结果表明，存在一个亚组谁似乎有增加的神经发育和精神病的责任。我们的研究结果强调了未来对这一高遗传风险患者群体的早期风险机制和早期干预研究的范围。虽然神经精神疾病通常在22q11.2DS的青春期后期出现，但我们的研究确定了儿童早期的一系列风险指标，表明了未来研究早期风险机制和早期干预的范围。
Individuals with 22q11.2 deletion are at considerably increased risk of neurodevelopmental and psychiatric conditions. There have been very few studies investigating how this risk manifests in early childhood and what factors may underlie developmental variability. Insights into this can elucidate transdiagnostic markers of risk that may underlie later development of neuropsychiatric outcomes. Thirty two children with 22q11.2 Deletion Syndrome (22q11.2DS) (mean age = 4.1 [SD = 1.2] years) and 12 sibling controls (mean age = 4.1 [SD = 1.5] years) underwent in‐depth dimensional phenotyping across several developmental domains selected as being potential early indicators of neurodevelopmental and psychiatric liability. Comparisons were conducted of the dimensional developmental phenotype of 22q11.2DS and sibling controls. For autistic traits, both parents and children were phenotyped using the Social Responsiveness Scale. Young children with 22q11.2DS exhibited large impairments (Hedge's g ≥ 0.8) across a range of developmental domains relative to sibling controls, as well as high rates of transdiagnostic neurodevelopmental and psychiatric traits. Cluster analysis revealed a subgroup of children with 22q11.2DS (n = 16; 53%) in whom neurodevelopmental and psychiatric liability was particularly increased and who differed from other children with 22q11.2DS and non‐carrier siblings. Exploratory analyses revealed that early motor and sleep impairments indexed liability for neurodevelopmental and psychiatric outcomes. Maternal autism trait scores were predictive of autism traits in children with 22q11.2DS (intraclass correlation coefficients = 0.47, p = 0.046, n = 31). Although psychiatric conditions typically emerge later in adolescence and adulthood in 22q11.2DS, our exploratory study was able to identify a range of early risk indicators. Furthermore, findings indicate the presence of a subgroup who appeared to have increased neurodevelopmental and psychiatric liability. Our findings highlight the scope for future studies of early risk mechanisms and early intervention within this high genetic risk patient group. Although neuropsychiatric conditions typically emerge later in adolescence in 22q11.2DS, our study identified a range of risk indicators in early childhood, indicating scope for future studies of early risk mechanisms and early intervention in this at‐risk patient group.