Delayed Circadian Rhythm in Adults with Attention-Deficit/Hyperactivity Disorder and Chronic Sleep-Onset Insomnia
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Background Previous studies suggest circadian rhythm disturbances in children with attention-deficit/hyperactivity disorder (ADHD) and sleep-onset insomnia (SOI). We investigate here sleep and rhythms in activity and melatonin in adults with ADHD.Methods Sleep logs and actigraphy data were collected during 1 week in 40 adults with ADHD, of whom 31 reported SOI. Salivary melatonin levels were assessed during 1 night. Sleep measures, circadian activity variables, and dim light melatonin onset were compared between groups of ADHD adults with and without SOI and with matched healthy control subjects.Results Compared with control subjects, both groups of ADHD adults had longer sleep-onset latency and lower sleep efficiency. Adults with ADHD and SOI showed a delayed start and end of their sleep period and a delayed melatonin onset compared with adults with ADHD without SOI (p = .006; p = .023; p = .02) and compared with healthy control subjects (p = .014; p = .019; p = .000). Adults with ADHD and SOI also showed an attenuated 24-hour amplitude in their rest-activity pattern, in contrast to those without SOI, who showed a higher day-to-day stability.Conclusions These findings demonstrate diurnal rhythm deviations during everyday life in the majority of adults with ADHD that have SOI and suggest that potential benefits of rhythm-improving measures should be evaluated.
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In 40 adults with ADHD, there is a delay of the diurnal cycle of activity/wake.
“Van Veen et al. (2010) report that in 40 adults with ADHD that there was a delay of the diurnal cycle of activity/wake and a delayed DLMO.”
From A systematic review of circadian function, chronotype and chronotherapy in attention deficit hyperactivity disorder (2017) · cites this paper as Van Veen et al. (2010)
In 40 adults with ADHD, there is a delayed DLMO.
“Van Veen et al. (2010) report that in 40 adults with ADHD that there was a delay of the diurnal cycle of activity/wake and a delayed DLMO.”
From A systematic review of circadian function, chronotype and chronotherapy in attention deficit hyperactivity disorder (2017) · cites this paper as Van Veen et al. (2010)
A number of studies have reported delayed DLMO in adults and children with ADHD.
“With regards to melatonin, as noted above a number of studies have reported delayed DLMO in adults and children with ADHD (van der Heijden et al. 2005, 2006; Van Veen et al. 2010; Bijlenga et al. 2013a).”
From A systematic review of circadian function, chronotype and chronotherapy in attention deficit hyperactivity disorder (2017) · cites this paper as Van Veen et al. 2010
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“Parallel findings have recently been obtained in adults with ADHD and SOI (significant differences between ADHD with and without SOI; Van Veen et al., 2010).”
ResultLugo, J., Fadeuilhe, C., Gisbert, L., Setien, I., Delgado, M., Corrales, M., Richarte, V., & Ramos-Quiroga, J. A. (2020) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2020.07.004 · Cited by 81 · see citing works
Bijlenga, D., Someren, E. J. W. V., Gruber, R., Bron, T. I., Kruithof, I. F., Spanbroek, E. C. A., & Kooij, J. J. S. (2013) · Journal of Sleep Research · doi:10.1111/jsr.12075 · Cited by 80 · see citing works
“The secretion of melatonin by the pineal gland of the brain is delayed in individuals with delayed sleep (Van Someren and Riemersma-Van Der Lek, 2007).”
BackgroundMethodResultInfluentialSelf-citationDifferential effects of theta/beta and SMR neurofeedback in ADHD on sleep onset latency
Arns, M., Feddema, I., & Kenemans, J. L. (2014) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2014.01019 · Cited by 79 · see citing works
“SOI is present in 72–78% of unmedicated children and adults with ADHD and in this subgroup of patients with SOI, a delayed DLMO has been found (delayed melatonin onset), suggestive of a circadian phase delay (Van der Heijden et al., 2005; Van Veen et al., 2010).”
BackgroundResultInfluentialRajagopal, V. M., Duan, J., Vilar‐Ribó, L., Grove, J., Zayats, T., Ramos‐Quiroga, J. A., Satterstrom, F. K., Artigas, M. S., Bybjerg‐Grauholm, J., Bækvad‐Hansen, M., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01143-7 · Cited by 76 · see citing works
The circadian rhythm in adult attention-deficit/hyperactivity disorder: current state of affairs
Kooij, J. J. S., & Bijlenga, D. (2013) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.2013.836301 · Cited by 78 · see citing works
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“One study reported that nearly four of five non-medicated ADHD participants suffered from sleep-onset insomnia (18), while other studies have found insomnia to be a side-effect of treatment with both stimulants (19) and atomoxetine (20).”
BackgroundMicic, G., de Bruyn, A., Lovato, N., Wright, H., Gradisar, M., Ferguson, S., Burgess, H. J., & Lack, L. (2013) · Journal of Sleep Research · doi:10.1111/jsr.12072 · Cited by 76 · see citing works
“For example, patients with sleep onset insomnia and ADHD tend to also exhibit significantly later timed phase markers (Boonstra et al., 2007; Lack et al., 2008; Van Veen et al., 2010), and perhaps a slower circadian oscillator may be contributing to the underlying mechanism that leads to their delay. ª 2013 European S…”
BackgroundYan, T. C., Dudley, J., Weir, R. K., Grabowska, E., Peña‐Oliver, Y., Ripley, T. L., Hunt, S. P., Stephens, D., & Stanford, S. C. (2011) · PLoS ONE · doi:10.1371/journal.pone.0017586 · Cited by 75 · see citing works
Circadian rhythms and attention deficit hyperactivity disorder: The what, the when and the why
Coogan, A. N., Baird, A. L., Popa‐Wagner, A., & Thome, J. (2016) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2016.01.006 · Cited by 73 · see citing works
“…which have been associated with both childhood and adult ADHD when comorbid with sleep onset insomnia, whereas both child and adult ADHD patients, who did not suffer from the sleep disorder, displayed normal dim light melatonin onset timing (Van der Heijden et al., 2005, Van Veen et al., 2010).”
InfluentialCarson, R. P., Fu, C., Winzenburger, P. A., & Ess, K. C. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds414 · Cited by 69 · see citing works
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“Alteration in sleep is notably frequent in patients with ADHD, and low melatonin levels as well as an abnormal delay of melatonin onset was reported in patients with ADHD and chronic sleep onset insomnia [4–6].”
BackgroundCodoñer‐Franch, P., Gombert, M., Martı́nez-Raga, J., & Cénit, M. C. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24087579 · Cited by 69 · see citing works
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“More than 70% of children and adults with ADHD also report insomnia (Fargason et al., 2013; Fargason et al., 2011, Gruber et al., 2012; Kessler et al., 2006; Van der Heijden et al., 2005; Van Veen et al., 2010).”
InfluentialGamble, K. L., May, R. S., Besing, R. C., Tankersly, A. P., & Fargason, R. E. (2013) · Chronobiology International · doi:10.3109/07420528.2012.754454 · Cited by 64 · see citing works
“…that our ADHD cohort was primarily comorbidity-free, which may explain why our patients did not have prolonged sleep latency, increased wake bouts, or decreased sleep efficiency compared with controls, as reported in other studies (Boonstra et al., 2007; Surman et al., 2009; Van Veen et al., 2010).”
BackgroundMethodResultInfluentialAssessment of Wakefulness and Brain Arousal Regulation in Psychiatric Research
Sander, C., Hensch, T., Wittekind, D. A., Böttger, D., & Hegerl, U. (2015) · Neuropsychobiology · doi:10.1159/000439384 · Cited by 64 · see citing works
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McGowan, N. M., Voinescu, B. I., & Coogan, A. N. (2016) · Chronobiology International · doi:10.1080/07420528.2016.1208214 · Cited by 59 · see citing works
“These changes include phase-delayed behavioural and endocrine rhythms (Baird et al., 2012; van Veen et al., 2010), desynchrony between melatonin secretion and sleep timing (Bijlinga et al., 2013), altered circadian clock gene expression (Baird et al., 2012) and, in terms of circadian typology, an…”
BackgroundYoon, J.-A., Han, D.-H., Noh, J.-Y., Kim, M.-H., Son, G. H., Kim, K., Kim, C., Pak, Y. K., & Cho, S. (2012) · PLoS ONE · doi:10.1371/journal.pone.0044053 · Cited by 59 · see citing works
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Circadian rhythm disruption as a link between Attention-Deficit/Hyperactivity Disorder and obesity?
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“About 78% of adults with ADHD have sleep-onset insomnia, a condition that is often present from childhood [14,15].”
BackgroundSelf-citationArns, M., Kooij, J. J. S., & Coogan, A. N. (2021) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2020.12.035 · Cited by 56 · see citing works
Self-citationGenome-wide copy number variation analysis in adult attention-deficit and hyperactivity disorder
Ramos‐Quiroga, J. A., Sánchez‐Mora, C., Casas, M., Iris Garcia-martinez, A., Bosch, R., Nogueira, M., Montse Corrales, F., Gloria Palomar, A., Vidal, R., Coll-Tané, M., et al. (2013) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2013.10.022 · Cited by 55 · see citing works
“In addition to the genes previously associated with ADHD or related phenotypes, such as the ones encoding the serotonin receptor 1B (HTR1B) or catechol-O-methyl transferase (COMT) (Bouwknecht et al., 2001; Brunner et al., 1999; Caylak, 2012; DeYoung et al.; Palmason et al., 2010; Ramboz et al., 1996; Salatino-Oliveira…”
BackgroundFatigue in an adult attention deficit hyperactivity disorder population: A trans‐diagnostic approach
Rogers, D. C., Dittner, A. J., Rimes, K. A., & Chalder, T. (2017) · British Journal of Clinical Psychology · doi:10.1111/bjc.12119 · Cited by 50 · see citing works
“Whilst many studies have focused on sleep-related difficulties in adult ADHD (Bijlenga et al., 2013; Fisher et al., 2014; Philipsen, Hornyak, & Riemann, 2006; Van Veen et al., 2010), there has been a dearth of research investigating fatigue.”
BackgroundRzepka-Migut, B., & Paprocka, J. (2020) · Brain Sciences · doi:10.3390/brainsci10040219 · Cited by 55 · see citing works
van Andel, E., Bijlenga, D., Vogel, S. W. N., Beekman, A. T. F., & Kooij, J. J. S. (2020) · Chronobiology International · doi:10.1080/07420528.2020.1835943 · Cited by 54 · see citing works
“Another one of our previous studies showed that 78% of adults with ADHD had a diagnosis of sleep-onset insomnia (SOI) and a delayed DLMO (Van Veen et al. 2010).”
BackgroundResultInfluentialSelf-citationParsons, C. E., Schofield, B. E., Batziou, S. E., Ward, C., & Young, K. S. (2021) · Journal of Sleep Research · doi:10.1111/jsr.13533 · Cited by 58 · see citing works
“Night- to- night sleep variability is common in the general population (e.g., Dillon et al., 2015; Knutson et al., 2007) and is especially marked in some clinical populations (e.g., attention deficit hyperactivity disorder; Van Veen et al., 2010).”
BackgroundThe hidden link between circadian entropy and mental health disorders
Alachkar, A., Lee, J., Asthana, K., Monfared, R. V., Chen, J., Alhassen, S., Samad, M., Wood, M., Mayer, E., & Baldi, P. (2022) · Translational Psychiatry · doi:10.1038/s41398-022-02028-3 · Cited by 65 · see citing works
Chronotherapeutics and psychiatry: Setting the clock to relieve the symptoms
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“In ADHD, circadian system dysfunctions are indicated by phase delays in the sleep/wake cycle with changes in diurnal preference towards greater eveningness, nocturnal rise in melatonin, and early morning increase in cortisol [57, 58, 64, 65].”
BackgroundMethylphenidate Modifies the Motion of the Circadian Clock
Antle, M. C., van Diepen, H. C., Deboer, T., Pedram, P., Pereira, R. R., & Meijer, J. H. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2012.103 · Cited by 52 · see citing works
Abuse-Deterrent and Tamper-Resistant Opioid Formulations
Schneider, J. P., Matthews, M. L., & Jamison, R. N. (2010) · CNS Drugs · doi:10.2165/11584260-000000000-00000 · Cited by 51 · see citing works
Wynchank, D., ten Have, M., Bijlenga, D., Penninx, B. W., Beekman, A. T., Lamers, F., de Graaf, R., & Kooij, J. J. S. (2018) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.6976 · Cited by 51 · see citing works
“40,41 19 Normal sleep duration was also found in two studies using self-report measures.”
Self-citationAttention‐ D eficit/ H yperactivity D isorder, P hysical H ealth, and L ifestyle in O lder A dults
Semeijn, E. J., Kooij, J. J. S., Comijs, H. C., Michielsen, M., Deeg, D. J. H., & Beekman, A. T. F. (2013) · Journal of the American Geriatrics Society · doi:10.1111/jgs.12261 · Cited by 48 · see citing works
Self-citationSleep and circadian rhythm function and trait impulsivity: An actigraphy study
McGowan, N. M., & Coogan, A. N. (2018) · Psychiatry Research · doi:10.1016/j.psychres.2018.07.030 · Cited by 46 · see citing works
Circadian Insights into Motivated Behavior
Antle, M. C., & Silver, R. (2015) · Current topics in behavioral neurosciences · doi:10.1007/7854_2015_384 · Cited by 47 · see citing works
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der Maren, S. V., Moderie, C., Duclos, C., Paquet, J., Daneault, V., & Dumont, M. (2018) · Journal of Biological Rhythms · doi:10.1177/0748730418757007 · Cited by 44 · see citing works
Molina-Carballo, A., Naranjo-Gómez, A., Uberos, J., Justicia-Martínez, F., Ruiz-Ramos, M.-J., Cubero-Millán, I., Contreras-Chova, F., Augustin-Morales, M.-D.-C., Khaldy-Belkadi, H., & Muñoz-Hoyos, A. (2013) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2012.09.020 · Cited by 43 · see citing works
Clock genes, ADHD and aggression
Mogavero, F., Jager, A., & Glennon, J. C. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.11.002 · Cited by 44 · see citing works
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“Furthermore, disease states with altered dopaminergic neurotransmission, such as Parkinson’s disease (PD) and attention deficit hyper-activity disorder (ADHD), are often associated with disturbed rest-activity profiles and sleep problems (Van Veen et al., 2010; Whitehead et al., 2008).”
The noradrenaline reuptake inhibitor atomoxetine phase-shifts the circadian clock in mice
O'Keeffe, S., Thome, J., & Coogan, A. N. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.11.002 · Cited by 43 · see citing works
“Circadian abnormalities, including phase-delays of the melatonin rhythms and delayed sleep-onset insomnia have been described in ADHD, as well as association with clock gene polymorphisms (Van Veen et al., 2010; Van der Heijden et al., 2005; Kissling et al., 2008).”
BackgroundBonvicini, C., Faraone, S. V., & Scassellati, C. (2016) · Molecular Psychiatry · doi:10.1038/mp.2016.128 · Cited by 42 · see citing works
Lee, S.-H., Kim, H.-B., & Lee, K.-W. (2019) · Journal of Affective Disorders · doi:10.1016/j.jad.2019.05.071 · Cited by 41 · see citing works
Circadian aspects in the aetiology and pathophysiology of insomnia
Lack, L. C., Micic, G., & Lovato, N. (2023) · Journal of Sleep Research · doi:10.1111/jsr.13976 · Cited by 41 · see citing works
Sciberras, E., Song, J. C., Mulraney, M., Schuster, T., & Hiscock, H. (2017) · European Child & Adolescent Psychiatry · doi:10.1007/s00787-017-1000-4 · Cited by 41 · see citing works
“There is evidence that sleep onset problems in children with ADHD are related to a delay in dim light melatonin onset, a marker of delayed circadian rhythms [11].”
BackgroundADHD 24/7: Circadian clock genes, chronotherapy and sleep/wake cycle insufficiencies in ADHD
Korman, M., Palm, D., Uzoni, A., Faltraco, F., Tucha, O. M., Thome, J., & Coogan, A. N. (2018) · The World Journal of Biological Psychiatry · doi:10.1080/15622975.2018.1523565 · Cited by 42 · see citing works
“Exogenous melatonin and melatoninergic agonists are shown to entrain the sleep–wake cycle, advance endogenous melatonin secretion and enhance total time asleep in children with ADHD and chronic SOI (Van der Heijden et al. 2007; Chamorro et al. 2017).”
BackgroundInfluentialHigh Prevalence of Self-Reported Photophobia in Adult ADHD
Kooij, J. J. S., & Bijlenga, D. (2014) · Frontiers in Neurology · doi:10.3389/fneur.2014.00256 · Cited by 40 · see citing works
“In the Van Veen study, there was a prevalence of 78% delayed sleep phase in a group of adults with ADHD (7).”
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Excessive Daytime Sleepiness in Patients With ADHD—Diagnostic and Management Strategies
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“If ADHD is not only associated with ID with predominant DIS and DMS, but also with predominant EMA, then ADHD could be viewed as an insomnia-related disorder rather than as a disorder related to a delayed sleep phase [10], which is characterized by DIS only [6].”
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Genetic deletion of MT1/MT2 melatonin receptors enhances murine cognitive and motor performance
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“Similarly to childhood ADHD, adult ADHD is also associated with sleep disturbances or circadian abnormalities.(1,2) Therefore, adult ADHD may also be related to the preference of morning/day activity (i.”
BackgroundMartín-Martínez, D., Casaseca‐de‐la‐Higuera, P., Alberola-López, S., Andrés-de-Llano, J., Villalobos, J. A. L., Ardura‐Fernandez, J., & Alberola‐López, C. (2012) · Medical Engineering & Physics · doi:10.1016/j.medengphy.2011.12.023 · Cited by 37 · see citing works
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Self-citationZerón-Rugerio, M. F., Carpio-Arias, T. V., Ferreira, E., Dı́ez-Noguera, A., Cambras, T., Alda, J. A., & Izquierdo-Pulido, M. (2020) · European Child & Adolescent Psychiatry · doi:10.1007/s00787-020-01659-5 · Cited by 35 · see citing works
- Authors
- Van Veen, M. M., Kooij, J. J. S., Boonstra, A. M., Gordijn, M. C. M., & Van Someren, E. J. W.
- Affiliations
- PsyQ (NL)
- University of Groningen (NL)
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2010-06
- Volume
- 67
- Issue
- 11
- Pages
- 1091-1096
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2105759166
- Cited by
- 300
- References
- 52
- Citations by year
- 2026: 10 · 2025: 21 · 2024: 19 · 2023: 16 · 2022: 16 · 2021: 27 · 2020: 21 · 2019: 19 · 2018: 18 · 2017: 16 · 2016: 25 · 2015: 17 · 2014: 18 · 2013: 14 · 2012: 22
- FWCI
- 22.89
- Type
- journal article
- Language
- en
- Open access
- green
- research.rug.nl
- Licence
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- VU Research Portal (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- Janssen Cilag BV
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Keywords
- attention deficit hyperactivity disorder, sleep onset insomnia, circadian rhythm, melatonin onset, sleep latency, sleep efficiency, rest-activity rhythm, actigraphy, salivary melatonin, adult ADHD
- MeSH terms
- Adolescent, Adult, Attention Deficit Disorder with Hyperactivity, Circadian Rhythm, Humans, Sleep Initiation and Maintenance Disorders, Melatonin, Middle Aged, Surveys and Questionnaires, Saliva, Sleep, Chi-Square Distribution, Actigraphy
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