Objective

Although there are frequent reports of shared neurofunctional and neurostructural alterations among probands with attention-deficit/hyperactivity disorder (ADHD) and their unaffected siblings, there is little knowledge regarding whether abnormalities in the resting-state functional connectivity of ADHD probands is also expressed in unaffected siblings, or whether this unaffected (but at-risk) cohort manifests distinct patterns.

Method

We used a multivariate connectome-wide association study examining intrinsic functional connectivity with resting-state functional magnetic resonance imaging (MRI) in a sample (aged 8−17 years) of medication-naive ADHD probands (n = 56), their unaffected siblings (n = 55), and typically developing (TD) youths (n = 106).

Results

ADHD probands showed, relative to TD youths, increased connectivity between the default-mode network (DMN) and task-positive networks. Relative to ADHD and TD groups, respectively, unaffected siblings showed increased connectivity within the salience network and reduced connectivity between the DMN and salience network. No shared alterations in functional connectivity among ADHD probands and their unaffected siblings were identified. These findings were largely confirmed by complementary pairwise connectomic comparisons. However, the main connectivity differences between ADHD and unaffected siblings were not replicated in a tightly age- and sex-matched subsample (20 proband−sibling pairs and 60 TD youths).

Conclusion

Our findings suggest that increased functional segregation related to the attention networks, especially the salience (ventral attention) system, may be a potential feature of at-risk siblings who remain unaffected by ADHD expression. Further replications are needed in other larger and sex-matched samples.

Clinical trial registration information: Structural and Functional Connectivity of Frontostriatal and Frontoparietal Networks as Endophenotypes of ADHD; https://clinicaltrials.gov/; NCT01682915.

中文翻译：

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未受影响兄弟姐妹患有注意力缺陷/多动症的年轻人中与显着网络有关的功能隔离增加

客观的

尽管经常有报告指出患有注意力缺陷/多动障碍（ADHD）的先证者及其未患兄弟姐妹共享神经功能和神经结构改变，但关于ADHD先证者的静息状态功能连接异常是否也未表达的知识却鲜为人知兄弟姐妹，或者这个未受影响（但处于危险中）的队列是否表现出截然不同的模式。

方法

我们使用了一个多变量全连接体关联研究，研究了未经药物治疗的多动症先证者（n = 56）（未患病兄弟姐妹）的样本（8-17岁）的内在功能与静息状态功能磁共振成像（MRI）的关联性（ n = 55），通常是发展中（TD）青年（n = 106）。

结果

与TD青年相比，ADHD先驱者表明，默认模式网络（DMN）与任务主动网络之间的连接性增强。相对于ADHD和TD组，未受影响的兄弟姐妹显示了显着网络内的连通性增加，而DMN和显着网络之间的连通性降低了。没有发现多动症先证者及其未受影响兄弟姐妹之间在功能连接上有共同的改变。这些发现在很大程度上被互补的成对结缔组织比较所证实。但是，ADHD和未受影响兄弟姐妹之间的主要连通性差异在年龄和性别匹配的子样本（20个先证者兄弟姐妹对和60个TD青年）中没有得到重复。

结论

我们的发现表明，与注意力网络相关的功能隔离增加，尤其是显着性（腹部注意力）系统，可能是高危兄弟姐妹的潜在特征，这些兄弟姐妹仍不受ADHD表达的影响。在其他较大且性别匹配的样本中，需要进一步复制。

临床试验注册信息：额叶和额顶网络的结构和功能连接作为多动症的内表型；https://clinicaltrials.gov/; NCT01682915。