TY - JOUR
T1 - Impact of adult attention deficit hyperactivity disorder and medication status on sleep/wake behavior and molecular circadian rhythms
AU - Coogan, A. N.
AU - Schenk, M.
AU - Palm, D.
AU - Uzoni, A.
AU - Grube, J.
AU - Tsang, A. H.
AU - Kolbe, I.
AU - McGowan, N. M.
AU - Wandschneider, R.
AU - Colla, M.
AU - Oster, H.
AU - Thome, J.
AU - Faltraco, F.
N1 - Funding Information:
Johannes Thome has received financial support from pharmaceutical companies (Actelion, Astra Zeneca, Bristol–Myers Squibb, EVER Neuro Pharma GmbH, Janssen-Cilag, Lilly, Lundbeck, MEDICE, Merz, Novartis, Pfizer, Roche, Servier, Shire, Trommsdorff) some of which manufacture medication used in the treatment of ADHD patients. Michael Colla received lecture fees from Eli Lilly, Janssen-Cilag, and Shire, acted as a consultant to Eli Lilly, Janssen-Cilag, and Shire, and received grants from the BMBF (Federal Ministry of Education and Research), the BMWi (Federal Ministry of Economics and Technology), and the EU (European Union). Andrew Coogan, Maria Schenk, Denise Palm, Adriana Uzoni, Jana Grube, Anthony Tsang, Isa Kolbe, Niall McGowan, Roland Wandschneider, Henrik Oster, and Frank Faltraco have no potential conflicts of interest to disclose.
Publisher Copyright:
© 2019, American College of Neuropsychopharmacology.
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2019/6/1
Y1 - 2019/6/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85065726676&partnerID=8YFLogxK
U2 - 10.1038/s41386-019-0327-6
DO - 10.1038/s41386-019-0327-6
M3 - Journal articles
C2 - 30758328
AN - SCOPUS:85065726676
SN - 0893-133X
VL - 44
SP - 1198
EP - 1206
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
IS - 7
ER -
