University of Groningen, University Medical Center Groningen, Department of Psychiatry, Groningen, The Netherlands.
University of Groningen, University Medical Center Groningen, Department of Psychiatry, Groningen, The Netherlands.
Eur Neuropsychopharmacol. 2016 Apr;26(4):674-83. doi: 10.1016/j.euroneuro.2016.02.007. Epub 2016 Feb 10.
Diffusion tensor imaging (DTI) has revealed white matter abnormalities in individuals with attention-deficit/hyperactivity disorder (ADHD). Stimulant treatment may affect such abnormalities. The current study investigated associations between long-term stimulant treatment and white matter integrity within the frontal-striatal and mesolimbic pathways, in a large sample of children, adolescents and young adults with ADHD. Participants with ADHD (N=172; mean age 17, range 9-26) underwent diffusion-weighted MRI scanning, along with an age- and gendermatched group of 96 control participants. Five study-specific white matter tract masks (orbitofrontal-striatal, orbitofrontal-amygdalar, amygdalar-striatal, dorsolateral-prefrontal-striatal and medialprefrontal-striatal) were created. First we analyzed case-control differences in fractional anisotropy (FA) and mean diffusivity (MD) within each tract. Second, FA and MD in each tract was predicted from cumulative stimulant intake within the ADHD group. After correction for multiple testing, participants with ADHD showed reduced FA in the orbitofrontal-striatal pathway (p=0.010, effect size=0.269). Within the ADHD group, higher cumulative stimulant intake was associated with lower MD in the same pathway (p=0.011, effect size=-0.164), but not with FA. The association between stimulant treatment and orbitofrontal-striatal MD was of modest effect size. It fell short of significance after adding ADHD severity or ADHD type to the model (p=0.036 and p=0.094, respectively), while the effect size changed little. Our findings are compatible with stimulant treatment enhancing orbitofrontal-striatal white matter connectivity, and emphasize the importance of the orbitofrontal cortex and its connections in ADHD. Longitudinal studies including a drug-naïve baseline assessment are needed to distinguish between-subject variability in ADHD severity from treatment effects.
弥散张量成像（DTI）显示注意力缺陷/多动障碍（ADHD）个体的白质异常。兴奋剂治疗可能会影响这些异常。本研究在一个大型 ADHD 儿童、青少年和年轻成人样本中，调查了长期兴奋剂治疗与前额纹状体和中边缘通路白质完整性之间的关联。ADHD 参与者（N=172；平均年龄 17 岁，范围 9-26 岁）接受了弥散加权 MRI 扫描，并与 96 名年龄和性别匹配的对照参与者进行了比较。创建了五个特定于研究的白质束掩模（眶额纹状体、眶额杏仁核、杏仁核纹状体、背外侧前额纹状体和内侧前额纹状体）。首先，我们分析了每个束中的分数各向异性（FA）和平均弥散度（MD）的病例对照差异。其次，根据 ADHD 组中累积兴奋剂摄入量预测每个束中的 FA 和 MD。在进行多次测试校正后，ADHD 参与者的眶额纹状体通路的 FA 降低（p=0.010，效应大小=0.269）。在 ADHD 组中，更高的累积兴奋剂摄入量与相同通路中的 MD 降低相关（p=0.011，效应大小=-0.164），但与 FA 无关。兴奋剂治疗与眶额纹状体 MD 之间的关联具有适度的效应大小。在将 ADHD 严重程度或 ADHD 类型添加到模型中后，该关联未达到显著水平（分别为 p=0.036 和 p=0.094），而效应大小变化不大。我们的研究结果与兴奋剂治疗增强眶额纹状体白质连接性的说法一致，并强调了前额叶皮层及其连接在 ADHD 中的重要性。需要进行包括药物初治基线评估的纵向研究，以区分 ADHD 严重程度的个体间变异性与治疗效果。
