Reports of sleep disturbances in attention deficit hyperactivity disorder (ADHD) are common in both children and adults; however, the aetiology of such disturbances is poorly understood. One potentially important mechanism which may be implicated in disrupted sleep in ADHD is the circadian clock, a known key regulator of the sleep/wake cycle. In this systematic review, we analyse the evidence for circadian rhythm changes associated with ADHD, as well as assessing evidence for therapeutic approaches involving the circadian clock in ADHD. We identify 62 relevant studies involving a total of 4462 ADHD patients. We find consistent evidence indicating that ADHD is associated with more eveningness/later chronotype and with phase delay of circadian phase markers such as dim light melatonin onset and delayed sleep onset. We find that there is evidence that melatonin treatment may be efficacious in addressing ADHD-related sleep problems, although there are few studies to date addressing other chronotherapeutic approaches in ADHD. There are only a small number of genetic association studies which report linkages between polymorphisms in circadian clock genes and ADHD symptoms. In conclusion, we find that there is consistent evidence for circadian rhythm disruption in ADHD and that such disruption may present a therapeutic target that future ADHD research might concentrate explicitly on.

Bipolar disorder (BD) and borderline personality disorder (BPD) are two psychiatric disorders with overlapping features that can be challenging to separate diagnostically. Growing evidence suggests that circadian rhythm disturbances are associated with psychiatric illness, however circadian patterns of behaviour have not been elucidated in BPD or differentiated from BD. This study compared the circadian structure and timing of rest-activity patterns in BPD with BD and healthy volunteers. Participants with BD ( N = 31) and BPD ( N = 21) and healthy controls (HC, N = 35) wore an actigraph on their non-dominant wrist for 28 day periods as part of the Automated Monitoring of Symptom Severity (AMoSS) study. Non-parametric circadian rhythm analysis of rest-activity patterns and cosinor analysis of distal temperature rhythms were conducted to elucidate circadian function between groups. Covariates controlled for included employment status, BMI and gender. Compared with HC and BD, individuals with BPD showed significantly delayed phase of night-time rest patterns (“L5 onset”) (mean difference = 1:47 h, P < 0.001; mean difference = 1:38 h, P = 0.009, respectively), and relative to HC showed delayed daytime activity onset (“M10 onset”) (mean difference = 2:13 h, P = 0.048) and delayed temperature phase (mean difference = 1:22 h, P = 0.034). These findings suggest that delayed circadian function may be a clinically important phenotype in individuals with BPD. Future work should interrogate the causality of this association and examine interventions which target delayed circadian function in the treatment of BPD.

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.

BackgroundDisruption of circadian rhythms is associated with several deleterious health consequences and cognitive impairment. It is estimated that as many as one in five workers are exposed to this risk factor due to experiencing some degree of chronodisruption by way of recurring patterns of shift work. It is not presently clear therefore how efficiently the mammalian circadian system entrains to alternative light/dark cycles such as those found in shift work schedules.MethodsThe present study examines male CD-1 mice exposed to three different paradigms of rapidly rotating shift work-like light/dark manipulations compared to control animals maintained on a standard 12:12 h light/dark cycle.ResultsAnalysis of circadian patterns of behaviour under such conditions reveals that for fast rotating schedules of light/dark there is minimal circadian entrainment. Further, when placed in constant conditions after a period under the “shift work” lighting conditions there were changes to circadian period associated with the shift work schedules. In contrast to previous studies the shift work-like conditions did not produce changes in animal body-weight. Behavioural testing suggests possible anxiogenic and hyperactive outcomes dependent on rotation speed as animals displayed open field thigmotaxis and hyperlocomotion.ConclusionThese results indicate that exposure to alternating patterns of light and dark as experienced by millions of shift workers may produce long-lasting changes in both mammalian circadian and neurobehavioural systems.