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Impact of adult attention deficit hyperactivity disorder and medication status on sleep/wake behavior and molecular circadian rhythms.
Neuropsychopharmacology ( IF 6.6 ) Pub Date : 2019-02-06 , DOI: 10.1038/s41386-019-0327-6
A N Coogan 1 , M Schenk 2 , D Palm 2 , A Uzoni 2 , J Grube 3 , A H Tsang 3 , I Kolbe 3 , N M McGowan 1, 4 , R Wandschneider 2 , M Colla 2 , H Oster 3 , J Thome 2 , F Faltraco 2
Affiliation  

Attention deficit hyperactivity disorder (ADHD) is a common neuropsychiatric condition that has been strongly associated with changes in sleep and circadian rhythms. Circadian rhythms are near 24-h cycles that are primarily generated by an endogenous circadian timekeeping system, encoded at the molecular level by a panel of clock genes. Stimulant and non-stimulant medication used in the management of ADHD has been shown to potentially impact on circadian processes and their behavioral outputs. In the current study, we have analyzed circadian rhythms in daily activity and sleep, and the circadian gene expression in a cohort of healthy controls (N = 22), ADHD participants not using ADHD-medication (N = 17), and participants with ADHD and current use of ADHD medication (N = 17). Rhythms of sleep/wake behavior were assessed via wrist-worn actigraphy, whilst rhythms of circadian gene expression were assessed ex-vivo in primary human-derived dermal fibroblast cultures. Behavioral data indicate that patients with ADHD using ADHD-medication have lower relative amplitudes of diurnal activity rhythms, lower sleep efficiency, more nocturnal activity but not more nocturnal wakenings than both controls and ADHD participants without medication. At the molecular level, there were alterations in the expression of PER2 and CRY1 between ADHD individuals with no medication compared to medicated ADHD patients or controls, whilst CLOCK expression was altered in patients with ADHD and current medication. Analysis of fibroblasts transfected with a BMAL1:luc reporter showed changes in the timing of the peak expression across the three groups. Taken together, these data support the contention that both ADHD and medication status impact on circadian processes.

中文翻译:

成人注意力缺陷多动障碍和药物状态对睡眠/觉醒行为和分子昼夜节律的影响。

注意力缺陷多动障碍(ADHD)是一种常见的神经精神疾病,与睡眠和昼夜节律的变化密切相关。昼夜节律接近 24 小时周期,主要由内源性昼夜节律计时系统产生,由一组时钟基因在分子水平上编码。用于治疗多动症的兴奋剂和非兴奋剂药物已被证明可能对昼夜节律过程及其行为输出产生影响。在当前的研究中,我们分析了日常活动和睡眠的昼夜节律,以及健康对照组 (N = 22)、未使用 ADHD 药物的 ADHD 参与者 (N = 17) 和 ADHD 参与者的昼夜节律基因表达以及目前 ADHD 药物的使用情况(N = 17)。通过腕带体动记录仪评估睡眠/觉醒行为节律,同时在原代人源真皮成纤维细胞培养物中离体评估昼夜节律基因表达节律。行为数据表明,与对照组和未服用药物的 ADHD 参与者相比,使用 ADHD 药物治疗的 ADHD 患者昼夜活动节律相对幅度较低、睡眠效率较低、夜间活动较多,但夜间觉醒次数并不多。在分子水平上,与接受药物治疗的 ADHD 患者或对照组相比,未接受药物治疗的 ADHD 个体中 PER2 和 CRY1 的表达发生了变化,而 ADHD 患者和当前药物治疗中的 CLOCK 表达发生了改变。对转染 BMAL1:luc 报告基因的成纤维细胞的分析显示,三组的峰值表达时间发生了变化。总而言之,这些数据支持了多动症和药物状态都会影响昼夜节律过程的论点。
更新日期:2019-02-06
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