Department of Neuroscience and Molecular Psychiatry, Institute of Life Science, School of Medicine, Swansea University, Swansea, UK.
Mol Psychiatry. 2012 Oct;17(10):988-95. doi: 10.1038/mp.2011.149. Epub 2011 Nov 22.
Attention-deficit hyperactivity disorder (ADHD) in adults is associated with impaired sleep, and it has been postulated that this impairment may contribute to the psychopathology of this common condition. One key driver of sleep/wake cycles is the circadian system, which at the molecular level consists of a series of transcriptional feedback loops of clock genes, which in turn produce endocrine, physiological and behavioural outputs with a near 24 h periodicity. We set out to examine circadian rhythms at the behavioural, endocrine and molecular levels in ADHD. Adults with ADHD as well as age- and sex-matched controls were recruited. Circadian rhythms were measured by means of actigraphy for the determination of gross motor patterns, by self-sampling of oral mucosa for assessment of rhythmic expression of the clock genes BMAL1 and PER2, and by estimation of salivary cortisol and melatonin levels. Actigraphic analysis revealed significant diurnal and nocturnal hyperactivity in the ADHD group, as well as a significant shorter period of best fit for the locomotor circadian rhythm in ADHD. BMAL1 and PER2 showed circadian rhythmicity in controls with this being lost in the ADHD group. Cortisol rhythms were significantly phase delayed in the ADHD group. These findings indicate that adult ADHD is accompanied by significant changes in the circadian system, which in turn may lead to decreased sleep duration and quality in the condition. Further, modulation of circadian rhythms may represent a novel therapeutic avenue in the management of ADHD.
成人注意缺陷多动障碍(ADHD)与睡眠障碍有关,据推测,这种损害可能导致这种常见疾病的精神病理学变化。睡眠/觉醒周期的一个关键驱动因素是昼夜节律系统,从分子水平上讲,它由一系列时钟基因的转录反馈环组成,这些基因反过来又产生具有近 24 小时周期性的内分泌、生理和行为输出。我们着手研究 ADHD 患者在行为、内分泌和分子水平上的昼夜节律。招募了患有 ADHD 的成年人以及年龄和性别匹配的对照组。通过活动记录仪测量昼夜节律,以确定大体运动模式,通过自我取样口腔粘膜评估时钟基因 BMAL1 和 PER2 的节律表达,通过估计唾液皮质醇和褪黑素水平来评估昼夜节律。活动记录仪分析显示,ADHD 组存在明显的日间和夜间过度活跃,以及 ADHD 组的运动昼夜节律最佳拟合周期明显缩短。对照组中 BMAL1 和 PER2 显示出昼夜节律性,而 ADHD 组则失去了这种节律性。皮质醇节律在 ADHD 组中明显延迟。这些发现表明,成人 ADHD 伴随着昼夜节律系统的显著变化,这反过来可能导致该病症的睡眠时间和质量下降。此外,昼夜节律的调节可能代表 ADHD 治疗管理中的一种新的治疗途径。