Shining a light on sleep in ADHD: ADHD, sleep, circadian rhythm, and health

Attention-Deficit/Hyperactivity Disorder (ADHD) is a neuropsychiatric condition characterised by a persistent pattern of inattention, hyperactivity, and/or impulsivity. Many adults with ADHD experience sleep problems that have often been present since childhood. A delayed circadian rhythm may be a shared underlying mechanism between ADHD and sleep problems. Up to 78% of adults with ADHD have a delayed rhythm characteristic of Delayed Sleep Phase Syndrome (DSPS). The general aim of this thesis is to shine a light on sleep in ADHD to gain more insight into the complex relationship between ADHD and sleep problems, with a particular focus on a delayed circadian rhythm and the effects of DSPS treatment. Insomnia is a common sleep problem in ADHD and may be a symptom of a delayed circadian rhythm. Using data from the large epidemiological study NEMESIS-2, we showed that mental functioning and productivity were more negatively affected if ADHD and insomnia symptoms co-occurred, even after controlling for comorbidities and other confounders. Further studies were based on data from the Phase Shift in ADHD of Sleep and Appetite (PhASE) study, a placebo-controlled randomised clinical trial investigating the effects of DSPS treatment in adults with ADHD and DSPS on circadian rhythm, ADHD symptoms, sleep, and physical health. In PhASE, 51 participants received sleep education followed by 3 weeks of placebo, melatonin, or melatonin plus bright light therapy (BLT); interventions targeted at advancing the circadian rhythm. The circadian rhythm advanced by 1.5-2 hours after treatment with melatonin or melatonin plus BLT, respectively. Furthermore, melatonin-only treatment reduced the ADHD symptoms by 14%: a clinically relevant finding. Unexpectedly, ADHD symptoms did not change in the melatonin + BLT group despite the rhythm advance. This was probably due to the fixed, early timing of BLT (between 07:00h-08:00h), which most participants found difficult and may have prevented any improvements in ADHD symptoms. Contrary to expectations, interventions did not advance sleep/wake times, lengthen or improve sleep, or strengthen the sleep-wake rhythm, despite improved sleep hygiene. So participants were physiologically able to fall asleep earlier, but this was not reflected by changes in sleep timing. Targeting the biology alone thus seems insufficient for changing long-standing sleep behaviours. ADHD and DSPS have been associated with chronic diseases such as obesity, diabetes, and cardiovascular diseases (CVDs). Despite a high occurrence of smoking and hypertension, the majority of participants had normal heart rate variability (HRV; a biomarker for cardiovascular risk). We thus found no evidence for current high risk of developing CVDs in our study population. Next, we focused on hormones involved in the regulation of appetite and glucose metabolism. Baseline appetite was low, which could be because measurements took place at 08:00h and thus during the biological night of these late-sleeping participants. Melatonin seemed to subtly increase appetite, possibly reflecting the advance in circadian rhythm. However, no such changes were seen in the melatonin + BLT group, despite the 2-hour advancement of the rhythm, which could again be due to the timing of BLT. By shining a light on sleep in ADHD, this thesis contributes to the growing insight into the intriguing relationship between ADHD, sleep, and the circadian rhythm. The findings underscore the importance of proper assessment and treatment of sleep problems in ADHD and vice versa. Treatment of DSPS in ADHD is probably most effective when tailored to the individual and consisting of a combination of individually timed chronotherapy and psychobehavioural interventions that target sleep specifically. Though there is still a lot more to learn, the current findings may help pave the way towards more effective diagnostics and treatment focusing on both ADHD and sleep.