Circadian rhythm disruption as a link between Attention-Deficit/Hyperactivity Disorder and obesity?
Introduction
Globally, obesity is a growing problem with serious health consequences, such as diabetes mellitus, cardiovascular diseases, musculoskeletal disorders, and cancer [1]. Worldwide, the prevalence of obesity has nearly doubled since 1980, with a current prevalence of 10% among men and 14% among women [2]. Obesity is more prevalent in psychiatric populations, including in patients with Attention-Deficit/Hyperactivity Disorder (ADHD) [3], [4]. ADHD is a disorder characterized by hyperactivity, impulsivity, and/or inattention [5]. A large population-based study showed that obesity was prevalent in 29% of adult ADHD patients in the US [6]. Vice versa, around 30% of obese adults have ADHD as observed in cross-sectional studies [7]. Moreover, longitudinal studies have found an association between childhood ADHD and obesity in adolescence or adulthood [8], [9].
Circadian rhythm disruption, more specifically a delayed circadian rhythm, may be a mechanism linking ADHD symptoms to obesity. In humans, behavioral and physiological processes, such as sleep and appetite hormones release, display approximately 24-hour rhythms, i.e., circadian rhythms [10]. Disturbances of these rhythms cause sleep disorders and disrupted eating patterns, among others [11], [12].
ADHD has been related to a delayed circadian rhythm, as indicated by an increased prevalence of Delayed Sleep Phase Syndrome (DSPS) in comparison to controls [13]. About 78% of adults with ADHD have sleep-onset insomnia, a condition that is often present from childhood [14], [15]. Some of these ADHD patients fulfill criteria for a diagnosis of DSPS, which include difficulty falling asleep at night and waking up in the morning causing impaired social and occupational functioning [16], [17], [18].
In the long term, DSPS may result in obesity in ADHD patients. DSPS often results in chronic sleep debt, especially when persons have social or work obligations in the early morning [19]. Epidemiological and clinical studies indicate that chronic short sleep is associated with a higher prevalence of obesity [20]. Specifically, a meta-analysis of 17 studies showed that adults who slept five hours or less per night had a 55% higher odds for obesity [21]. Furthermore, lower levels of the appetite-reducing hormone leptin and higher levels of the appetite-stimulating hormone ghrelin have been found in short sleepers, leading to increased food craving and appetite [22]. Clinically, we have observed that ADHD patients with comorbid DSPS exhibit unstable eating patterns, characterized by skipping breakfast and binge eating later in the day, which may be mediated by a disrupted release of appetite hormones. An unstable eating pattern has a prominent role in weight gain and obesity [23].
In short, there are associations between ADHD symptoms, delayed sleep, and obesity. We recently compared these relationships in adults with ADHD and a control group [24]. Associations were found between hyperactivity, delayed sleep, binge eating, and high body mass index (BMI), both in the ADHD group as well as in the control group. In the present study, we extend our previous research by adding a group of participants with obesity. Given the high prevalence of DSPS in ADHD patients, and the association of this circadian rhythm disturbance with obesity, we hypothesized that circadian rhythm disruption may be a mechanism linking ADHD symptoms to obesity. Therefore, we expect to find that (1) the obesity group will have a higher prevalence of ADHD symptoms, sleep problems, and an unstable eating pattern than the control group, but a lower prevalence of these factors than the ADHD group; and that (2) circadian rhythm disruption, as indicated by sleep duration and an unstable eating pattern, is a mechanism linking ADHD symptoms to obesity, even after controlling for known confounders such as sociodemographics and current depression/anxiety symptoms [25], [26]. Although previous researchers [27], [28] have hypothesized that short sleep disruption may play a role in the association between ADHD symptomatology and obesity, no one has tested this hypothesis in adult ADHD patients. If circadian rhythm disruption is involved in the association between ADHD symptoms and obesity, this may provide clinical opportunities for the development of new chronobiological treatment strategies in patients with obesity and/or ADHD, hence improving health in the long term.
Section snippets
Obesity group
Participants were included with a diagnosis of obesity, defined as a BMI ≥ 30 kg/m2, based on self-reported weight and height [2]. Participants who were not fluent in Dutch were excluded from the study. We recruited 114 participants with obesity aged 18 to 65 years old, between February 2011 and April 2013 from the PsyQ outpatient clinics for eating disorders and obesity, in The Hague and Rotterdam (n = 13), from the Center for Obesity Europe in Heerlen (n = 77), from a XL Fair, a lifestyle event for
ADHD symptoms
Severity of ADHD symptoms was measured using the Dutch self-report version of the ADHD-Rating Scale (ADHD-RS) [30]. The validated ADHD-RS is based on the DSM-IV criteria for ADHD, and consists of 23 items on current ADHD symptoms and 23 items on childhood ADHD symptoms, all rated on a 4-point Likert scale ranging from 0 (never or rarely) to 3 (very often) [31]. A score of ≥ 23 in adulthood indicated high ADHD symptoms [24].
Manifestations of circadian disruption
We used manifestations of sleep problems and an unstable eating pattern
Obesity group
We calculated BMI using self-reported weight and height [2]. The participants filled out the questionnaires on paper.
ADHD and control groups
During diagnostic assessment, the ADHD group filled out the questionnaires with pen and paper. The control group completed an online version of the questionnaires. A more detailed procedure for the inclusion of the ADHD and controls groups has been described in Bijlenga et al. (2013) [24]. According to the prevailing Dutch Medical Research Involving Human Subjects Act, medical
General characteristics
Table 1 compares the general characteristics between the obese, ADHD, and control groups (total N = 470). Participants with obesity were significantly older and contained more females than the ADHD and control group. Compared to ADHD patients, obese subjects more often had a higher vocational status, were less often current smokers, less often consumed over 15 alcoholic beverages per week, and performed less physical activity. Compared to controls, participants with obesity were more often
Discussion
In this study, we found that participants with obesity had a higher prevalence of ADHD symptoms and short sleep on free days as compared to controls, but a lower prevalence of ADHD symptoms, short sleep duration, and an unstable eating pattern as compared to ADHD patients. However, contrary to our expectations, participants with obesity had a comparable prevalence rate of an unstable eating pattern as compared to controls. Therefore, these results only partially support our first hypothesis
Conflict of interest
All authors have completed the Unified Competing Interest form at http://www.icmje.org/coi_disclosure.pdf and declare that Dr. Beekman has been a speaker for Lundbeck and Eli Lily in the past three years that could be perceived to constitute a conflict of interest. The other authors have no competing interests to report.
Acknowledgments
We thank all participants of the study, and the PsyQ outpatient clinics, Program Eating Disorders and Obesity in The Hague and Rotterdam, CO-Eur in Heerlen, Prof. Dr. A. Jansen and her team from the Maastricht University, and the staff of PsyQ Program Adult ADHD in The Hague for their time and effort to include patients in the study. We also thank Dr. D. Wynchank for checking the English language of the manuscript. This study was funded by the PsyQ Research Fund. The funding sources had no
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