Attention-deficit hyperactivity disorder (ADHD) is characterized by changes to the circadian process. Many medications used to treat the condition, influence norepinephrine levels. Several studies have, in addition, reported that norepinephrine itself has an effect on circadian function. The aim of this study was to investigate the circadian gene expression in primary human-derived dermal fibroblast cultures (HDF) after norepinephrine exposure. We analyzed circadian preference, behavioral circadian and sleep parameters as well as the circadian gene expression in a cohort of healthy controls and participants with an ADHD diagnosis. Circadian preference was evaluated with German Morningness–Eveningness Questionnaire (D-MEQ) and rhythms of sleep/wake behavior were assessed via actigraphy. After ex vivo exposure to different norepinephrine concentrations in HDF cultures, the rhythmicity of circadian gene expression was analyzed via qRT-PCR. The exposure of 1 µM norepinephrine to confluent cultures of human dermal fibroblasts from participants with a diagnosis of ADHD, was shown to dampen Per1 rhythmicity. The expression of Bmal1, Per1 and Per3 in control subjects was also influenced by incubation with 1 µM norepinephrine. Cultures from the ADHD group revealed no statistically significant overall differences in circadian gene expression, between cultures with and without norepinephrine incubation. Per3 expression showed a significant ZT × group interaction via mixed ANOVA. Per3 expression at ZT4 was significant higher in the group of control samples incubated with 1 µM norepinephrine, compared to the control group without norepinephrine. This effect was also shown in the control samples incubated with 1 µM norepinephrine and cultures from subjects with ADHD without norepinephrine incubation. Per3 expression differed between the healthy control group and the ADHD group without norepinephrine incubation at ZT28. The results of the present study illustrate that norepinephrine impacts on circadian function. In both groups, control group and cultures taken from subjects with ADHD, the expression of the periodic genes (Per1–3) was significantly influenced by incubation with norepinephrine.

注意缺陷多动障碍 (ADHD) 的特点是昼夜节律过程发生变化。许多用于治疗该病的药物都会影响去甲肾上腺素水平。此外，几项研究报告说，去甲肾上腺素本身对昼夜节律功能有影响。本研究的目的是研究去甲肾上腺素暴露后原代人源性真皮成纤维细胞培养 (HDF) 中的昼夜节律基因表达。我们分析了一组健康对照组和患有 ADHD 诊断的参与者的昼夜节律偏好、行为昼夜节律和睡眠参数以及昼夜节律基因表达。昼夜节律偏好通过德国晨昏问卷 (D-MEQ) 进行评估，睡眠/清醒行为的节律通过活动记录仪进行评估。离体后在 HDF 培养物中暴露于不同浓度的去甲肾上腺素，通过 qRT-PCR 分析昼夜节律基因表达的节律性。将 1 µM 去甲肾上腺素暴露于来自被诊断为 ADHD 的参与者的人类真皮成纤维细胞融合培养物中，被证明会抑制Per1节律性。对照受试者中Bmal1、Per1和Per3的表达也受到与 1 µM 去甲肾上腺素孵育的影响。ADHD 组的培养物显示，在有和没有去甲肾上腺素孵育的培养物之间，昼夜节律基因表达没有统计学上显着的总体差异。Per3表达通过混合方差分析显示出显着的 ZT × 组相互作用。Per3与没有去甲肾上腺素的对照组相比，在用 1 µM 去甲肾上腺素孵育的对照样品组中，ZT4 的表达显着更高。这种效果也显示在与 1 µM 去甲肾上腺素孵育的对照样品中，以及来自患有 ADHD 的受试者的培养物中，而没有去甲肾上腺素孵育。在 ZT28 没有去甲肾上腺素孵育的健康对照组和 ADHD 组之间的Per3表达不同。本研究的结果表明去甲肾上腺素影响昼夜节律功能。在两组、对照组和取自 ADHD 受试者的培养物中，周期性基因( Per1-3 ) 的表达受到去甲肾上腺素孵育的显着影响。