Impact of adult attention deficit hyperactivity disorder and medication status on sleep/wake behavior and molecular circadian rhythms

Coogan, Andrew N.; Schenk, Mariela; Palm, D.; Uzoni, Adriana; Grube, Jordon G.; Tsang, Anthony H.; Kolbe, Isa; McGowan, Niall M.; Wandschneider, Roland; Colla, Michael; Oster, Henrik; Thome, Johannes; Faltraco, Frank

doi:10.1038/s41386-019-0327-6

Cited by 31 publications

(35 citation statements)

References 48 publications

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“…Pain may also be a driver of insomnia and short sleep duration in somatic health conditions, but may also be bidirectional as insomnia has been linked to increased pain perceptions ( Wei et al, 2018 ; McCrae et al, 2019 ). Medications may also impact sleep across mental and somatic disorders, including a positive effect of symptom management, but such drugs may also impact sleep negatively, as observed in conditions such as ADHD ( Coogan et al, 2019 ) and epilepsy ( Jain and Glauser, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

The Epidemiology of Insomnia and Sleep Duration Across Mental and Physical Health: The SHoT Study

et al. 2021

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ObjectiveNumerous epidemiological studies have been conducted to examine the prevalence and comorbidities of insomnia and document sleep duration, but a common limitation in many studies is the lack of use of agreed-upon definitions of insomnia, as well as insufficient statistical power to examine comorbid mental and physical disorders/conditions.AimTo examine the prevalence of insomnia operationalized according to formal DSM-5 criteria and differences in mean sleep duration across a wide range of mental and physical disorders, examining men and women separately.Materials and MethodsData stem from the SHoT study (Students’ Health and Wellbeing Study), a national survey of all college and university students in Norway. In all, 162,512 students aged 18–35 received an invitation to participate, of whom 50,054 students completed the internet-based survey (attendance rate: 30.8%). Insomnia was defined according to the Diagnostic and Statistical Manual of Mental Disorders (5th ed.) criteria and sleep duration was calculated separately for weekdays and weekends. Self-reported mental and physical disorders/conditions were assessed using a pre-defined list modified to fit this age group. Pearson chi-squared tests were used to examine the prevalence of insomnia across the various mental and physical disorders/conditions in men and women separately, and log-link binomial regression analysis were used to calculate effect-sizes, adjusting for age.ResultsThe prevalence of insomnia in both sexes was significantly higher across all mental disorders compared with a healthy reference group. Among females, the prevalence of insomnia ranged from 61.3% for comorbid depression (adj. RR = 2.49, 95% CI: 2.40) to 83.3% for comorbid schizophrenia (adj. RR = 3.37, 95% CI: 2.61–4.35). For males, the insomnia prevalence ranged from 32.3% for comorbid autism/Asperger (adj. RR = 2.02, 95% CI: 1.39–2.92) to 74.2% for comorbid eating disorder (adj. RR = 4.51, 95% CI: 3.87–5.27). The overall prevalence of insomnia was also significantly higher across most physical conditions compared with the healthy reference group, although generally lower compared to the mental disorders. For females, the insomnia prevalence ranged from 25% for comorbid multiple sclerosis (not significant) to 65.4% for comorbid chronic fatigue syndrome/ME (adj. RR = 2.66, 95% CI: 2.44–2.89). For males, the insomnia prevalence ranged from 20% for both comorbid cancer and diabetes (not significant) to 74.2% for comorbid fibromyalgia (adj. RR = 4.35, 95% CI: 2.96–6.39). Similar patterns were observed for sleep duration, with a significantly shorter sleep duration for across many physical disorders, but especially mental disorders.ConclusionInsomnia and short sleep duration are strongly associated with a range of different disorders and conditions. Insomnia is most strongly associated with mental disorders, and physical conditions characterized by some level of psychological or psychosomatic properties.

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Section: Discussionmentioning

confidence: 99%

The Epidemiology of Insomnia and Sleep Duration Across Mental and Physical Health: The SHoT Study

et al. 2021

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“…Several studies have implicated altered circadian function in attention deficit hyperactivity disorder (ADHD), with typical findings indicating delayed circadian phase, later chronotype and impaired sleep duration and/or quality (Coogan & McGowan, 2017; Coogan et al, 2019). It is not presently clear whether such circadian and sleep behaviour changes are risk factors for, or symptoms of, ADHD.…”

Section: Introductionmentioning

confidence: 99%

The impact of social jetlag and chronotype on attention, inhibition and decision making in healthy adults

McGowan

Uzoni

Faltraco

et al. 2020

Journal of Sleep Research

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Circadian rhythms are recurring cycles displaying periods of nearly twenty-four hours, which are present in a range of behavioural, physiological and cognitive processes (Buttgereit, Smolen, Coogan, & Cajochen, 2015). Circadian rhythms interact with homeostatic sleep pressure to shape the timing of sleep (Borbély, Daan, Wirz-Justice, & Deboer, 2016). An important manifestation of these circadian traits in human behaviour is chronotype, reflecting the tendency to structure daily activities, including sleep-wake times, according to the underpinning circadian clock (Roenneberg, Wirz-Justice, & Merrow, 2003). Chronotype is also associated with psychological domains, including personality, impulsivity and psychopathology (Li et al., 2018). Furthermore, chronotype is associated with optimal timing of daily performance in a number of cognitive tasks, with a synchrony effect existing between time of testing and chronotype for many cognitive domains (such that late chronotypes perform better later in the day, early chronotypes earlier in the day; Schmidt, Collette, Cajochen, & Peigneux, 2007). Heritability of chronotype is estimated at approximately 50% and recent genome-wide studies have identified a number of clock and non-clock genes associated with a modest portion of trait variance (Kalmbach et al., 2017). For appropriate entrainment of the circadian clock to environmental zeitgebers, the clock responds to both the zeitgeber timing and intensity to shape chronotype (Roenneberg, Kumar, & Merrow, 2007). Age and sex also profoundly influence chronotype throughout the lifespan (Fischer, Lombardi, Marucci-Wellman, & Roenneberg, 2017). One consequence of a later chronotype is a propensity to experience greater levels of social jetlag (SJL): the mismatch between internal biological time and socially driven behavioural schedules suggested to produce chronic circadian misalignment (Wittmann,

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“…Circadian rhythms are driven by the central pacemaker in the mammalian brain, the suprachiasmatic nucleus (SCN) of the hypothalamus, also entrained in peripheral cells including fibroblasts cultured in vitro (Balsalobre 1998;Schibler and Sassone-Corsi 2002). Our research group observed circadian gene alterations at the molecular level of human dermal fibroblasts derived from human individuals (ADHD and control subjects) (Coogan 2019). Human-derived fibroblasts provide an advantageous model to study circadian rhythmicity as well as the influence of drugs on circadian gene expression (Faltraco et al 2020).…”

Section: Introductionmentioning

confidence: 97%

“…High-dose methylphenidate suppresses intracranial selfstimulation, suggesting the possibility that methylphenidate treatment does not increase the risk of drug dependence (Ide et al 2018). Using HDF as a model, Coogan et al (2019) report alterations in the expression of Per2 and Cry1 between subjects with ADHD without medication, compared to ADHD subjects taking medication, or controls. Clock gene expression was also altered in pharmaceutically treated ADHD subjects.…”

Section: Introductionmentioning

confidence: 99%

“…Analysis of fibroblasts transfected with a Bmal1:luc reporter demonstrated changes in the timing of the peak expression across the three groups. Behavioral data that indicate that patients with ADHD using ADHD medication have lower relative amplitudes of diurnal activity rhythms, lower sleep efficiency and more nocturnal activity (Coogan et al 2019).…”

Section: Introductionmentioning

confidence: 99%

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Dopamine adjusts the circadian gene expression of Per2 and Per3 in human dermal fibroblasts from ADHD patients

et al. 2021

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A link between dopamine levels, circadian gene expression, and attention deficit hyperactivity disorder (ADHD) has already been demonstrated. The aim of this study was to investigate the extent of these relationships by measuring circadian gene expression in primary human-derived dermal fibroblast cultures (HDF) after dopamine 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 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 dopamine concentrations in human dermal fibroblast (HDF) cultures, the rhythmicity of circadian gene expression (Clock, Bmal1, Per1-3, Cry1) was analyzed via qRT-PCR. We found no statistical significant effect in the actigraphy of both groups (healthy controls, ADHD group) for mid-sleep on weekend days, mid-sleep on weekdays, social jetlag, wake after sleep onset, and total number of wake bouts. D-MEQ scores indicated that healthy controls had no evening preference, whereas subjects with ADHD displayed both definitive and moderate evening preferences. Dopamine has no effect on Per3 expression in healthy controls, but produces a significant difference in the ADHD group at ZT24 and ZT28. In the ADHD group, incubation with dopamine, either 1 µM or 10 µM, resulted in an adjustment of Per3 expression to control levels. A similar effect also was found in the expression of Per2. Statistical significant differences in the expression of Per2 (ZT4) in the control group compared to the ADHD group were found, following incubation with dopamine. The present study illustrates that dopamine impacts on circadian function. The results lead to the suggestion that dopamine may improve the sleep quality as well as ADHD symptoms by adjustment of the circadian gene expression, especially for Per2 and Per3.

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Impact of adult attention deficit hyperactivity disorder and medication status on sleep/wake behavior and molecular circadian rhythms

Cited by 31 publications

References 48 publications

The Epidemiology of Insomnia and Sleep Duration Across Mental and Physical Health: The SHoT Study

The Epidemiology of Insomnia and Sleep Duration Across Mental and Physical Health: The SHoT Study

The impact of social jetlag and chronotype on attention, inhibition and decision making in healthy adults

Dopamine adjusts the circadian gene expression of Per2 and Per3 in human dermal fibroblasts from ADHD patients

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