Atomoxetine (ATO) is a second line medication for attention-deficit hyperactivity disorder (ADHD). We proposed that part of the therapeutic profile of ATO may be through circadian rhythm modulation. Thus, the aim of this study was to investigate the circadian gene expression in primary human-derived dermal fibroblast cultures (HDF) after ATO 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 a diagnosis of ADHD. 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 ATO concentrations in HDF cultures, the rhythmicity of circadian gene expression was analyzed via qRT-PCR. No statistical significant effect of both groups (healthy controls, ADHD group) for mid-sleep on weekend days, mid-sleep on weekdays, social jetlag, sleep WASO and total number of wake bouts was observed. D-MEQ scores indicated that healthy controls had no evening preference, whereas subjects with ADHD displayed both definitive and moderate evening preferences. ATO induced the rhythmicity of Clock in the ADHD group. This effect, however, was not observed in HDF cultures of healthy controls. Bmal1 and Per2 expression showed a significant ZT × group interaction via mixed ANOVA. Strong positive correlations for chronotype and circadian genes were observed for Bmal1, Cry1 and Per3 among the study participants. Statistical significant different Clock, Bmal1 and Per3 expressions were observed in HDFs exposed to ATO collected from ADHD participants exhibiting neutral and moderate evening preference, as well as healthy participants with morning preferences. The results of the present study illustrate that ATO impacts on circadian function, particularly on Clock, Bmal1 and Per2 gene expression.

托莫西汀 (ATO) 是治疗注意力缺陷多动障碍 (ADHD) 的二线药物。我们提出，ATO 的部分治疗特征可能是通过昼夜节律调节。因此，本研究的目的是研究 ATO 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和诊断为 ADHD 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-晚上问卷 (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 ATO 浓度，通过 qRT-PCR 分析昼夜节律基因表达的节律性。两组（健康对照组、ADHD 组）在周末睡眠中、工作日中睡眠、社交时差、睡眠 WASO 和清醒发作总数方面均未观察到统计学显着影响。D-MEQ 评分表明健康对照组没有晚间偏好，而患有 ADHD 的受试者则表现出明确和中度的晚间偏好。ATO诱导ADHD组Clock的节律性。然而，在健康对照的 HDF 培养物中没有观察到这种效果。Bmal1和Per2表达通过混合方差分析显示出显着的 ZT × 组相互作用。在研究参与者中观察到Bmal1、Cry1和Per3的计时型和昼夜节律基因存在强正相关。在暴露于 ATO 的 HDF 中观察到统计学上显着不同的Clock、Bmal1和Per3表达，这些 HDF 是从表现出中性和中度夜间偏好的 ADHD 参与者以及具有早晨偏好的健康参与者收集的。本研究的结果表明，ATO 影响昼夜节律功能，特别是对Clock、Bmal1和Per2基因表达的影响。