Objective:

Psychostimulants are first-line pharmacological treatments for attention deficit hyperactivity disorder (ADHD), although symptom reduction varies widely between patients and these individual differences in treatment response are poorly understood. The authors sought to examine whether the resting-state functional connectivity within and between cingulo-opercular, striato-thalamic, and default mode networks was associated with treatment response to psychostimulant medication, and whether this relationship changed with development.

Methods:

Patients with ADHD (N=110; 196 observations; mean age at first observation, 10.83 years, SD=2.2) and typically developing control subjects (N=142; 330 observations; mean age at first observation, 10.49 years, SD=2.81) underwent functional neuroimaging on up to five occasions during development (age range, 6–17 years). For patients, symptoms were assessed on and off psychostimulant medication (methylphenidate-based treatments: N=132 observations, 67%; amphetamine-based treatments: N=64 observations, 33%) using the Diagnostic Interview for Children and Adolescents for parents. Linear mixed-effects models examined whether resting-state connectivity was associated with treatment response and its interaction with age. Comparisons with typically developing control subjects were performed to contextualize any significant associations.

Results:

Resting-state connectivity within the cingulo-opercular network was associated with a significant interaction between treatment response and age. Specifically, worse responses to treatment compared with better responses to treatment among patients and compared with typically developing control subjects were associated with an atypical increase in cingulo-opercular connectivity with increasing age from childhood to adolescence.

Conclusions:

This work delineates how resting-state connectivity may be associated over development with response to psychostimulants in ADHD. Functioning and development within the cingulo-opercular network may warrant further investigation as a contributor to differential response to psychostimulants.

中文翻译：

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ADHD 静息态连通性和精神兴奋剂治疗反应的纵向研究

客观的：

精神兴奋剂是注意力缺陷多动障碍（ADHD）的一线药物治疗方法，尽管不同患者的症状减轻效果差异很大，而且治疗反应的个体差异尚不清楚。作者试图研究扣带-盖骨、纹状体-丘脑和默认模式网络内部和之间的静息态功能连接是否与精神兴奋药物的治疗反应相关，以及这种关系是否随着发育而改变。

方法：

ADHD 患者（N=110；196 次观察；首次观察时的平均年龄，10.83 岁，SD=2.2）和典型发育对照受试者（N=142；330 次观察；首次观察时的平均年龄，10.49 岁，SD=2.81）在发育过程中（年龄范围，6-17 岁）接受了多达五次功能性神经影像检查。对于患者，使用儿童和青少年诊断访谈对父母进行精神兴奋药物治疗和停药期间的症状评估（基于哌醋甲酯的治疗：N=132 次观察，67%；基于安非他明的治疗：N=64 次观察，33%）。线性混合效应模型检查静息态连接是否与治疗反应及其与年龄的相互作用相关。与典型发育对照受试者进行比较，以了解任何显着关联。

结果：

扣带-盖网络内的静息态连接与治疗反应和年龄之间的显着相互作用相关。具体而言，与患者对治疗的更好反应相比，以及与正常发育的对照受试者相比，对治疗的反应较差与随着从童年到青春期年龄的增加，扣带-盖骨连接性的非典型增加有关。

结论：

这项工作描述了静息态连接如何与多动症患者对精神兴奋剂的反应与发育过程相关。扣带-鳃盖网络内的功能和发育可能需要进一步研究，作为对精神兴奋剂的差异反应的贡献者。