ADHD as a circadian rhythm disorder: evidence and implications for chronotherapy (2025)

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ADHD as a circadian rhythm disorder: evidence and implications for chronotherapy (2025)

Accumulating evidence indicates that circadian rhythm dysfunction is a clinically significant and highly prevalent phenotype in a substantial subgroup of individuals with Attention-Deficit/Hyperactivity Disorder (ADHD). This perspective synthesizes convergent lines of evidence demonstrating strong associations between ADHD and evening chronotype with phase-delayed biological markers. Sleep disturbances are profound: insomnia and sleep disturbances affect up to 80% of adults with ADHD and similarly up to 82% of children with ADHD, delayed sleep-wake timing occurs in up to 78%, and dim-light melatonin onset (DLMO) is delayed by approximately 45 minutes in children and 90 minutes in adults. These alterations coincide with blunted and delayed cortisol rhythms, reduced pineal volume, and attenuated peripheral clock-gene rhythms (BMAL1/PER2).

越来越多的证据表明，昼夜节律功能障碍是注意力缺陷多动障碍（ADHD）患者中一个具有临床意义且高度普遍的表型。本文综述了多项趋同证据，证明了 ADHD 与晚睡型（evening chronotype）及生物标志物相位延迟之间的强关联。睡眠障碍问题十分严重：高达 80% 的 ADHD 成年人和 82% 的 ADHD 儿童受到失眠和睡眠障碍的困扰；高达 78% 的患者出现睡眠-觉醒时间延迟；儿童和成年人的褪黑素分泌起始时间（DLMO）分别延迟了约 45 分钟和 90 分钟。这些改变伴随着皮质醇节律的减弱与延迟、松果体体积的减小以及外周生物钟基因节律（BMAL1/PER2）的衰减。

Intervention studies demonstrate that the circadian phase can be successfully advanced in ADHD populations. Melatonin and bright light therapy has advanced DLMO in both children and adults with ADHD. Emerging data correlate phase advancement with ADHD symptom improvement, and winter trials suggest circadian preference shifts best predict symptom improvement. Sleep programs improve ADHD symptoms, sleep quality, and functioning in children. Exercise and multimodal protocols for evening chronotypes successfully advance circadian timing in non-ADHD populations and warrant investigation in ADHD.

干预研究表明，ADHD 群体的昼夜节律相位可以得到有效提前。褪黑素和强光疗法已成功使 ADHD 儿童和成人的 DLMO 提前。新兴数据将相位提前与 ADHD 症状改善联系起来，冬季试验表明，昼夜节律偏好的转变是预测症状改善的最佳指标。睡眠项目可改善儿童的 ADHD 症状、睡眠质量和功能。针对晚睡型的运动和多模式方案已在非 ADHD 人群中成功提前了昼夜节律时间，值得在 ADHD 患者中进一步研究。

Based on this evidence, we propose a pragmatic, behavioral-first clinical pathway: routine screening for sleep/circadian disturbances; phenotypic characterization through chronotype assessment, sleep tracking, and DLMO when feasible; implementation of fixed wake times, morning bright light exposure, evening light restriction with screen hygiene, and regularized zeitgebers; and selective low-dose melatonin for confirmed or probable DLMO delays.

基于上述证据，我们提出了一种务实的、以行为干预为先的临床路径：对睡眠/昼夜节律障碍进行常规筛查；通过时型评估、睡眠追踪以及在可行时进行 DLMO 检测来进行表型表征；实施固定的起床时间、早晨强光照射、晚间光线限制及屏幕卫生管理，并规律化授时因子（zeitgebers）；对于已确认或疑似 DLMO 延迟的患者，选择性使用低剂量褪黑素。

Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder characterized by impaired levels of inattention, hyperactivity, and impulsivity (1). There is a growing body of research identifying that ADHD has a significant sleep and circadian component (2, 3). Insomnia is present in up to 80% of adults with ADHD and similarly high rates (up to 82%) of children with ADHD (4, 5). Converging evidence indicates that circadian rhythm disruption represents a highly prevalent and clinically important phenotype that interacts with ADHD symptoms in complex, bidirectional ways in a substantial proportion (though not all) of individuals. In parallel, clinical trials have begun targeting the circadian system and have demonstrated that phase shifting the internal clock of people with ADHD can improve symptoms.

注意力缺陷多动障碍（ADHD）是一种常见的神经发育障碍，其特征为注意力不集中、多动和冲动水平受损（1）。越来越多的研究表明，ADHD 具有显著的睡眠和昼夜节律成分（2, 3）。高达 80% 的 ADHD 成年人和同样高比例（高达 82%）的 ADHD 儿童存在失眠问题（4, 5）。趋同的证据表明，昼夜节律紊乱是一种高度普遍且具有临床重要性的表型，它在很大一部分（尽管并非全部）个体中以复杂、双向的方式与 ADHD 症状相互作用。与此同时，临床试验已开始针对昼夜节律系统进行干预，并证明通过改变 ADHD 患者的生物钟相位可以改善症状。

Herein, we propose the adoption of behavioral circadian interventions as adjuncts in ADHD care. This circadian-informed approach is a pragmatic, scalable, and generally low risk. We invite rigorously future well-designed, stratified trials to quantify effects on core ADHD outcomes, define responder phenotypes, and optimize circadian-focused protocols.

在此，我们建议将行为昼夜节律干预作为 ADHD 护理的辅助手段。这种基于昼夜节律的方法务实、可扩展且风险普遍较低。我们期待未来进行设计严谨的分层试验，以量化其对 ADHD 核心结果的影响，定义应答者表型，并优化以昼夜节律为重点的方案。

An estimated 73-78% of children and adults with ADHD have a delayed sleep/wake cycle (6). These findings persist even in the absence of comorbid mental health conditions, with multiple independent studies confirming elevated rates of self-reported sleep problems in adults with ADHD (7). These subjective reports are corroborated by objective sleep studies, which demonstrate that sleep onset latency and sleep efficiency problems remain significantly associated with ADHD even after controlling for anxiety and depression (8).

据估计，73-78% 的 ADHD 儿童和成人存在睡眠/觉醒周期延迟（6）。即使在没有共病心理健康状况的情况下，这些发现依然存在；多项独立研究证实，ADHD 成年人自我报告的睡眠问题发生率较高（7）。这些主观报告得到了客观睡眠研究的证实，研究表明，即使在控制了焦虑和抑郁因素后，入睡潜伏期和睡眠效率问题仍与 ADHD 显著相关（8）。

A comprehensive systematic review found robust evidence for evening chronotype predominance in ADHD (2). Approximately three-quarters of adults who developed ADHD in childhood show objective evidence of phase-delayed circadian rhythms. Biological markers such as dim-light melatonin onset in saliva, core body temperature rhythms, and actigraphically-recorded sleep patterns are typically shifted later by roughly 90 minutes compared to neurotypical adults (9).

一项全面的系统综述发现了 ADHD 患者中晚睡型占主导地位的有力证据（2）。约四分之三在童年时期患有 ADHD 的成年人表现出昼夜节律相位延迟的客观证据。与神经典型成年人相比，唾液褪黑素分泌起始时间、核心体温节律以及通过体动记录仪记录的睡眠模式等生物标志物通常会延迟约 90 分钟（9）。

Phase delays of melatonin in both individuals with ADHD have been well characterized, with children and adults identified to have a delayed onset of about 45 minutes and 90 minutes, respectively (10). Beyond the phase delay of melatonin onset in ADHD, there is evidence that the amount and pattern of melatonin production may differ (Figure 1). Some studies have observed abnormally high levels of melatonin during the day in children with ADHD, which improves with methylphenidate treatment (6). This ability to suppress daytime melatonin levels and shift the melatonin rhythm earlier suggests a complex interplay between ADHD medications and circadian systems. Individuals with ADHD have also been found to have smaller pineal gland (which produces and secretes melatonin) volume compared to healthy controls, with a positive correlation between pineal gland volume and eveningness (11).

ADHD 患者的褪黑素相位延迟特征已被充分描述，研究发现儿童和成人的褪黑素分泌起始时间分别延迟了约 45 分钟和 90 分钟（10）。除了褪黑素分泌起始的相位延迟外，还有证据表明褪黑素的产生量和模式可能存在差异（图 1）。一些研究观察到 ADHD 儿童在白天存在异常高的褪黑素水平，而这种现象可以通过哌甲酯治疗得到改善（6）。这种抑制白天褪黑素水平并使褪黑素节律提前的能力，暗示了 ADHD 药物与昼夜节律系统之间存在复杂的相互作用。研究还发现，与健康对照组相比，ADHD 患者的松果体（负责产生和分泌褪黑素）体积较小，且松果体体积与晚睡倾向之间存在正相关关系（11）。

Circadian hormone profiles (melatonin and cortisol) in ADHD. Conceptual 24-h curves (dashed = ADHD; solid = neurotypical controls) illustrate a later dim-light melatonin onset (DLMO), reduced nocturnal melatonin amplitude, and occasionally higher daytime melatonin levels, alongside a later and flatter morning cortisol rise/peak in ADHD. Curves are conceptual (not to scale), and individual findings vary by age, comorbidity, and light exposure. This figure was created with BioRender.com.

ADHD 患者的昼夜节律激素（褪黑素和皮质醇）概况。概念性的 24 小时曲线（虚线 = ADHD；实线 = 神经典型对照组）展示了 ADHD 患者较晚的褪黑素分泌起始时间（DLMO）、降低的夜间褪黑素振幅、有时较高的白天褪黑素水平，以及较晚且平缓的早晨皮质醇上升/峰值。曲线为概念性展示（未按比例绘制），个体结果因年龄、共病和光照情况而异。此图由 BioRender.com 创建。

ADHD also involves blunted and delayed cortisol rhythms (Figure 1) (12, 13). In an analysis of adults with ADHD compared to age- and sex-matched controls, adults with ADHD

ADHD 还涉及减弱和延迟的皮质醇节律（图 1）（12, 13）。在一项将 ADHD 成年人与年龄和性别匹配的对照组进行比较的分析中，ADHD 成年人……