BACKGROUND Twin studies show that age-related change in symptoms of attention-deficit/hyperactivity disorder (ADHD) is heritable. However, we do not know the heritability of the development of the neural substrates underlying the disorder. Here, we estimated the heritability of developmental change in white matter tracts and the brain's intrinsic functional connectivity using longitudinal data. We further determined associations with change in ADHD symptoms. METHODS The study reports on 288 children, which included 127 siblings, 19 cousins, and 142 singletons; 150 (52%) had a diagnosis of ADHD (determined by clinician interview with parent); 188 were male. All had two clinical assessments (overall baseline mean age: 9.4 ± 2.4 years; follow-up: 12.5 ± 2.6 years). Diffusion tensor imaging estimated microstructural properties of white matter tracts on 252 participants. Resting-state functional magnetic resonance imaging estimated intrinsic connectivity within and between major brain networks on 226 participants. Total additive genetic heritability (h2) of the annual rate of change in these neural phenotypes was calculated using SOLAR (Sequential Oligogenic Linkage Analysis Routines). RESULTS Significant heritability was found for the rates of change of 6 white matter tract microstructural properties and for change in the connectivity between the ventral attention network and both the cognitive control and dorsal attention networks. Change in hyperactivity-impulsivity was associated with heritable change in white matter tracts metrics and change in the connectivity between the ventral attention and cognitive networks. CONCLUSIONS The relatively small number of heritable, ADHD-associated developmental neural phenotypes can serve as phenotypes for future gene discovery and understanding.

中文翻译：

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估计神经连接发育变化的遗传力，及其与注意力缺陷多动障碍症状变化的关联。

背景 双胞胎研究表明，注意力缺陷/多动障碍 (ADHD) 症状的年龄相关变化是可遗传的。然而，我们不知道该疾病背后的神经基质发育的遗传性。在这里，我们使用纵向数据估计了白质束发育变化和大脑内在功能连接的遗传力。我们进一步确定了与 ADHD 症状变化的关联。方法研究报告了288名儿童，其中包括127名兄弟姐妹、19名堂兄弟和142名单身人士；150 (52%) 人被诊断为 ADHD（由临床医生与父母面谈确定）；188 人是男性。所有人都有两次临床评估（总体基线平均年龄：9.4 ± 2.4 岁；随访：12.5 ± 2.6 岁）。扩散张量成像估计了 252 名参与者的白质束的微观结构特性。静息状态功能磁共振成像估计了 226 名参与者的主要大脑网络内部和之间的内在连通性。使用 SOLAR（序列寡基因连锁分析程序）计算这些神经表型的年变化率的总加性遗传遗传力 (h2)。结果 发现 6 个白质束微结构特性的变化率以及腹侧注意网络与认知控制和背侧注意网络之间的连接性变化具有显着的遗传性。多动冲动的变化与白质束指标的可遗传变化以及腹侧注意力和认知网络之间连接性的变化有关。结论 相对较少的可遗传的、ADHD 相关的发育神经表型可以作为未来基因发现和理解的表型。