Adult attention-deficit hyperactivity disorder is associated with alterations in circadian rhythms at the behavioural, endocrine and molecular levels

Mol Psychiatry. 2012 Oct;17(10):988-95. doi: 10.1038/mp.2011.149. Epub 2011 Nov 22.

Abstract

Attention-deficit hyperactivity disorder (ADHD) in adults is associated with impaired sleep, and it has been postulated that this impairment may contribute to the psychopathology of this common condition. One key driver of sleep/wake cycles is the circadian system, which at the molecular level consists of a series of transcriptional feedback loops of clock genes, which in turn produce endocrine, physiological and behavioural outputs with a near 24 h periodicity. We set out to examine circadian rhythms at the behavioural, endocrine and molecular levels in ADHD. Adults with ADHD as well as age- and sex-matched controls were recruited. Circadian rhythms were measured by means of actigraphy for the determination of gross motor patterns, by self-sampling of oral mucosa for assessment of rhythmic expression of the clock genes BMAL1 and PER2, and by estimation of salivary cortisol and melatonin levels. Actigraphic analysis revealed significant diurnal and nocturnal hyperactivity in the ADHD group, as well as a significant shorter period of best fit for the locomotor circadian rhythm in ADHD. BMAL1 and PER2 showed circadian rhythmicity in controls with this being lost in the ADHD group. Cortisol rhythms were significantly phase delayed in the ADHD group. These findings indicate that adult ADHD is accompanied by significant changes in the circadian system, which in turn may lead to decreased sleep duration and quality in the condition. Further, modulation of circadian rhythms may represent a novel therapeutic avenue in the management of ADHD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ARNTL Transcription Factors / genetics*
  • Actigraphy
  • Adult
  • Attention Deficit Disorder with Hyperactivity* / genetics
  • Attention Deficit Disorder with Hyperactivity* / metabolism
  • Attention Deficit Disorder with Hyperactivity* / physiopathology
  • Case-Control Studies
  • Circadian Rhythm / physiology*
  • Diagnostic and Statistical Manual of Mental Disorders
  • Endocrine System / physiopathology*
  • Female
  • Humans
  • Hydrocortisone / metabolism
  • Male
  • Melatonin / metabolism
  • Middle Aged
  • Period Circadian Proteins / genetics*
  • Psychometrics
  • Retrospective Studies
  • Saliva / metabolism
  • Self Report
  • Statistics, Nonparametric
  • Surveys and Questionnaires
  • Time Factors
  • Young Adult

Substances

  • ARNTL Transcription Factors
  • BMAL1 protein, human
  • PER2 protein, human
  • Period Circadian Proteins
  • Melatonin
  • Hydrocortisone