Annual variation in attentional response after methylphenidate treatment

  • Madelon A. VollebregtEmail author
  • J. Leon Kenemans
  • Jan K. Buitelaar
  • Tom Deboer
  • Sean W. Cain
  • Donna Palmer
  • Glen R. Elliott
  • Evian Gordon
  • Kamran Fallahpour
  • Martijn Arns
Original Contribution


Prevalence rates of attention-deficit/hyperactivity disorder (ADHD) differ with geographical areas varying in sunlight intensity. Sun- or daylight reaching the retina establishes entrainment of the circadian clock to daylight. Changes herein, hence, alterations in clock alignment, could be reflected indirectly in inattention via sleep duration. We here studied (1) annual variation in inattention at treatment initiation; (2) annual variation in response to ADHD treatment [methylphenidate (MPH)] by day of treatment initiation; and (3) dose dependence. We predicted least baseline inattention during a period of high sunlight intensity implying more room for improvement (i.e., a better treatment response) when sunlight intensity is low. These hypotheses were not confirmed. High-dose treated patients, however, had significantly better attention after treatment than low-dosed treated patients, only when treated in the period from winter to summer solstice. Change in solar irradiance (SI) during low-dosed treatment period was negatively related to attentional improvement. The above described findings were primarily found in inattention ratings and replicated in omission errors on a continuous performance task. Daylight and inattention have been proposed to be related via mediation of the circadian system. One mechanism of MPH may be to enhance sensitivity to the diurnal entrainment to sunlight and the question can be raised whether appropriate lighting could potentiate the effects of stimulants.


Methylphenidate ADHD Sunlight Inattention Annual variation 



We acknowledge the iSPOT-A Investigators Group, the contributions of iSPOT-A principal investigators at each site, and the central management team (global coordinator Claire Day, PhD).

Compliance with ethical standards

Conflict of interest

MA reports research grants and options from Brain Resource (Sydney, Australia) and shares from neuroCare Group (Munich, Germany); DP has received income and stock options with the role of science and data processing manager as an employee with Brain Resource Ltd.; EG is founder and receives income as Chief Executive Officer and Chairman for Brain Resource Ltd. He has stock options in Brain Resource Ltd. JKB has been a consultant to/member of advisory board of/and/or speaker for Janssen Cilag BV, Eli Lilly, and Servier in the past years. He is not an employee of any of these companies, and not a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents, royalties. MV, LK, TD, and GE report no financial disclosures.

Ethical approval

The study complies with the principles of the “Declaration of Helsinki 2008,” the International Conference on Harmonization (ICH) guidelines, and the laws and regulations of the country in which the research is conducted, including the principles of “Good Clinical Practice” as outlined in the U.S. Code of Federal Regulations. All sites received approval from their Institutional Review Board (IRB)/Independent Ethics Committee (IEC) prior to participant enrollment and each participant (and/or guardian) provided their informed consent to be involved in the study.

Supplementary material

787_2019_1434_MOESM1_ESM.docx (617 kb)
Supplementary material 1 (DOCX 616 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Madelon A. Vollebregt
    • 1
    Email author
  • J. Leon Kenemans
    • 3
  • Jan K. Buitelaar
    • 2
    • 4
  • Tom Deboer
    • 5
  • Sean W. Cain
    • 6
  • Donna Palmer
    • 7
    • 8
    • 9
  • Glen R. Elliott
    • 10
    • 11
  • Evian Gordon
    • 7
    • 8
  • Kamran Fallahpour
    • 12
    • 13
  • Martijn Arns
    • 1
    • 3
    • 14
  1. 1.Research Institute BrainclinicsBrainclinics FoundationNijmegenThe Netherlands
  2. 2.Department of Cognitive Neuroscience, Radboud University Medical CentreDonders Institute for Brain, Cognition and BehaviourNijmegenThe Netherlands
  3. 3.Department of Experimental PsychologyUtrecht UniversityUtrechtThe Netherlands
  4. 4.Karakter Child and Adolescent Psychiatry University CentreNijmegenThe Netherlands
  5. 5.Laboratory for Neurophysiology, Department of Cell and Chemical BiologyLeiden University Medical CenterLeidenThe Netherlands
  6. 6.School of Psychological Sciences and Monash Institute of Cognitive and Clinical NeurosciencesClaytonAustralia
  7. 7.Brain Resource LtdSydneyAustralia
  8. 8.Brain Resource LtdSan FranciscoUSA
  9. 9.Brain Dynamics Center, Sydney Medical School and Westmead Millenium InstituteUniversity of SydneySydneyAustralia
  10. 10.Children’s Health CouncilPalo AltoUSA
  11. 11.Department of Psychiatry and Behavioral SciencesStanford School of MedicineStanfordUSA
  12. 12.Icahn School of Medicine at Mount SinaiNew YorkUSA
  13. 13.Brain Resource CenterNew YorkUSA
  14. 14.neuroCare GroupMunichGermany

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