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research-article2015

JADXXX10.1177/1087054714561291Journal of Attention DisordersRoy et al.

Article

Association Between Restless Legs Syndrome and Adult ADHD in a German Community-Based Sample

Journal of Attention Disorders 1­–9 © 2015 SAGE Publications Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1087054714561291 jad.sagepub.com

Mandy Roy1, Martina de Zwaan1, Inka Tuin2, Alexandra Philipsen3, Elmar Brähler2,4, and Astrid Müller1

Abstract Objective: Previous research in clinical samples indicated a significant association between ADHD and restless legs syndrome (RLS). The present study examined the association between adult ADHD and RLS in the German population. Method: Self-rating instruments to assess RLS, childhood ADHD, and adult ADHD were administered to a communitybased sample (N = 1,632). In addition, current depression and anxiety, sleep disturbances, weight, and height were assessed by self-report. Results: Adult ADHD was associated with statistically significant increases in the odds of meeting diagnostic criteria for RLS even when adjusting for potential confounding variables such as weight (odds ratio [OR] = 3.18, 95% confidence interval [CI] = [1.29, 7.63], p< .001). However, the association did not hold true after adjusting for the presence of sleep disturbances (OR = 2.02, 95% CI = [0.82, 4.96], p = .13). Conclusion: The findings suggest a strong link between RLS and adult ADHD symptoms. Clinicians should be aware of RLS among adult ADHD patients, especially as there might be a negative interactive effect. (J. of Att. Dis. XXXX; XX(X) XX-XX) Keywords adult ADHD, restless legs syndrome, sleep disturbances, general population

Introduction Restless legs syndrome (RLS) is a sensorimotor disorder characterized by an irresistible inner urge to move the legs and by sensory discomfort in the lower legs. The paresthetic or dysesthetic limb sensations are worse at rest and in the evenings or nights, which leads to sleep disturbances (Allen et al., 2003; Walters, 1995). Idiopathic RLS affects patients without any other comorbid disorder that can explain the symptoms. Symptomatic forms of RLS can appear due to several other somatic conditions, for example, anemia, renal failure, iron deficiency, polyneuropathies, or during pregnancy (Symvoulakis, Anyfantakis, & Lionis, 2010). There is no significant difference between the idiopathic and symptomatic forms of the disease in terms of clinical symptomatology or phenotype indicating a similar underlying pathophysiology (Ondo & Jankovic, 1996). Prevalence rates of RLS in community-based samples range between 5% and 14% (Ohayon, O’Hara, & Vitiello, 2012). For example, the prevalence of RLS in a representative northeastern German community-based sample (N = 4,310) aged 20 to 79 years was found to be 10.6%, increasing with age (Berger, Luedemann, Trenkwalder, John, & Kessler, 2004). RLS is known to be highly comorbid with sleep disturbances (Allen et al., 2003; Ohayon et al., 2012). Furthermore, RLS appears to be strongly linked to depression and/or anxiety

(Hornyak, 2010; Ohayon et al., 2012; D. Picchietti et al., 2007). Also, an association between RLS and obesity has been found in many studies; however, less consistently (Gao, Schwarzschild, Wang, & Ascherio, 2009; Phillips et al., 2000). Furthermore, previous research has shown that RLS appears to be more frequent in patients with ADHD than in controls and, in turn, that patients with ADHD commonly suffer from RLS (Cortese et al., 2005; Lewin & Di Pinto, 2004; D. Picchietti et al., 2007; M. A. Picchietti & Picchietti, 2010; Walters, Silvestri, Zucconi, Chandrashekariah, & Konofal, 2008). It should be emphasized that in children, RLS can also be associated with oppositional behaviors, such as bedtime refusal, which may confound its relationship with ADHD (Cortese, Lecendreux, Mouren, & Konofal, 2006). There exists evidence that childhood as well as adult ADHD is associated with high psychiatric comorbidity, 1

Hannover Medical School, Germany University of Mainz, Germany 3 University of Oldenburg, Germany 4 University of Leipzig, Germany 2

Corresponding Author: Mandy Roy, Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany. Email: [email protected]

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including depression and anxiety (Cumyn, French, & Hechtman, 2009; Sobanski et al., 2007). Also, obesity (Cortese et al., 2008; de Zwaan et al., 2011; Gruss, Mueller, Horbach, Martin, & de Zwaan, 2012; Sobanski et al., 2007) and sleep disturbances (Konofal, Lecendreux, & Cortese, 2010; Philipsen, Hornyak, & Riemann, 2006; Schredl, Alm, & Sobanski, 2007; Yoon, Jain, & Shapiro, 2012) are common among individuals with ADHD. While most studies have focused on the association between RLS and ADHD in childhood, so far, only few studies have examined this topic in adults. Wagner et al. (2004) described increased ADHD symptoms in 62 adult patients with RLS compared with 32 patients with insomnia and 77 healthy controls. In contrast, in the study published by Gamaldo et al. (2007), the prevalence of ADHD was not increased among adults with RLS. They had examined the co-occurrence of RLS and specific adult behaviors and childhood factors, potentially related to the development of RLS, in a case-controlled family history study (N = 973, 27% with RLS). These results should be interpreted carefully as they may have been influenced by the fact that the diagnosis of ADHD in this study was based solely on one item from a retrospective telephone interview clearly limiting the validity of the conclusion. Steinlechner (2011) found increased prevalence rates of RLS and psychiatric disorders including ADHD in parents of 26 children with ADHD. Philipsen et al. (2005) reported increased nocturnal motor activity among 20 adult ADHD patients using polysomnography and sleep encephalogram spectral power analysis. These findings were confirmed by others reporting elevated prevalence rates of RLS symptoms based on selfratings and interviews in adult ADHD patients (Schredl et al., 2007; Zak, Fisher, Couvadelli, Moss, & Walters, 2009). Taken together, previous findings suggest an association between RLS and ADHD not only among children but also among adults. However, most studies were conducted in clinical samples of patients with RLS or patients with ADHD. To date, little is known about this relationship in the general population. Therefore, the present study aimed to examine the postulated association between RLS and adult ADHD in a large representative population-based sample. We expected to find a similar relationship in the community as in clinical samples. Given the knowledge regarding the link between RLS and ADHD to depressive and anxiety symptoms, to sleep disturbances as well as to obesity, we also assessed these variables and carried out regression analyses adjusting for them.

Method Recruitment and Sample A random sample of the German general population was selected with the assistance of a demographic consulting company (USUMA, Berlin, Germany). The sample was

selected to be representative in terms of age, sex, and education. The area of Germany was separated into 258 sample areas representing the different regions of the country. Households of the respective area and members of the household fulfilling the inclusion criteria (age at or above 14, able to read and understand the German language) were selected randomly. The household respondent was selected using a random process (Kish selection grid). A first attempt was made for 4,091 addresses, of which 4,069 were valid. If not at home, a maximum of three attempts was made to contact the selected person. All participants were visited by a study assistant, who informed them about the investigation, obtained written informed consent, and presented them with the self-rating questionnaires (see below). The assistant waited until participants answered all questionnaires and offered help if persons did not understand the meaning of questions. A total of 2,520 people between the ages of 14 and 93 years agreed to participate and completed the selfrating questionnaires (participation rate: 61.9% of valid addresses) between November 27 and December 16, 2009. Given the assumed inaccuracy in terms of retrospective recall of childhood symptoms and the reduced validity of the self-rating instruments for childhood and current ADHD symptoms in older adults, we decided to exclude all respondents whose age was above 64 years (n = 695) for the present study. As this study focused on adult ADHD, we further excluded data from all participants aged below 18 years (n = 100). In addition, participants who did not fully complete the central diagnostic instruments concerning ADHD and RLS symptoms and those who did not present weight and height data were excluded from analyses. This provided a final sample of 1,632 individuals for analysis. The population-based survey met the ethical guidelines of the international Code of Marketing and Social Research Practice by the International Chamber of Commerce and the European Society for Opinion and Marketing Research. The study was approved by the Ethics Committee of the University of Leipzig.

Assessment In accordance with earlier studies (Berger et al., 2004; Hogl et al., 2005; Ohayon & Roth, 2002), RLS symptomatology was assessed with three questions, adapted from the recommendations established by the International Restless Legs Symptom Study Group (IRLSSG) that were valid in the year 2009 when the survey was carried out. Thus, the minimal criteria of RLS laid down in 1995 were applied (Walters, 1995). Participants were asked to answer the following three questions with “Yes” or “No”: (a) Do you have sensory discomfort such as tingling, crawling with ants, or pain in the legs, associated with an urge to move? (b) Do these symptoms occur at rest, that is, while sitting down or falling asleep, and do they improve when you move? and (c) Are

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Roy et al. these symptoms worse in the evening or at night compared with morning? The “double” criterion in Question 2 was only rated as positive if both aspects were affirmed and all three primary features (Questions 1-3) had to be met to be classified as RLS positive. Participants were asked about the frequency of occurrence and only individuals meeting the minimal requirement of at least five lifetime events were included (Allen, 2014). Thus, the diagnosis of RLS in the present study also fulfilled the revised “essential” criteria for RLS published in 2003 (Allen et al., 2003). Participants were asked to rate their ADHD symptoms in childhood retrospectively, using the German version of the short version of the Wender Utah Rating Scale (WURS-k), which consists of 25 items on a 5-point Likert-type scale (0-4, “not at all” to “severe”; Retz-Junginger et al., 2002; Rösler, Retz-Junginger, Retz, Stieglitz, 2008). The internal consistency in our sample was .92 (Cronbach’s α). As suggested by the authors, we used a cutoff score of ≥30 to indicate the presence of childhood ADHD (age 8-10 years). This cutoff had a sensitivity of 85% and a specificity of 75% in an earlier validation study (Retz-Junginger et al., 2003). Adult ADHD symptoms were assessed with the ADHD self-rating scale (ADHD-SR), which includes the 18 Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV;American Psychiatric Association, 1994) items of inattention, hyperactivity, and impulsivity on a 4-point Likert-type scale (0-3, “not at all” to “severe”; Rösler et al., 2008; Rösler et al., 2004). Cronbach’s alpha in our sample was .92. When comparing self-rating with expert rating, good agreement was found as measured by intraclass coefficients for individual symptoms (0.41-0.92) and for the total score (0.87) in an earlier study (Rösler et al., 2004). Rösler et al. (2004) recommended a cutoff of ≥15 to classify individuals with adult ADHD. They reported a sensitivity of 77% and a specificity of 75% for this cutoff. In the present study, only participants who fulfilled both the WURS-k criteria and the ADHD-SR criteria were diagnosed as probable cases of adult ADHD. Based on the participants’ self-reported height and weight, the body mass index (BMI, [kg/m2]) was calculated. For the purpose of the present study, three BMI categories were created: under/normal-weight (BMI ≤ 25 kg/m2), overweight (BMI = 25.1-29.9 kg/m2), and obesity (BMI ≥ 30 kg/m2). We used the German version (Löwe et al., 2010) of the four-item Patient Health Questionnaire (PHQ-4; Kroenke, Spitzer, Williams, &Löwe, 2009) to assess depression and anxiety symptoms for the last 2 weeks. This self-rating consists of a two-item depression scale (PHQ-2) and a two-item anxiety scale (Generalized Anxiety Disorder [GAD]-2) answered from 0 (“not at all”) to 3 (“nearly every day”). Löwe et al. (2010) reported a cutoff of ≥6 as being indicative for the presence of a depressive or an anxiety disorder, representing a percentile of 95.7% in a large population-based sample (N = 5,030). Therefore, participants who presented with a total

PHQ-4 score equal to or above 6 were classified as suffering from depression/anxiety in the present study. Sleep quality and the presence of sleep complaints were assessed using the German version of the four-item Jenkins Sleep Scale (JSS) that addresses problems with sleep onset, nocturnal or early-morning awakenings, sleep maintenance, and subjective ratings of feeling rested (Jenkins, Stanton, Niemcryk, & Rose, 1988; Salo et al., 2010). Respondents were asked to rate how often they experienced the described symptoms during the last month from 0 (“not at all”) to 5 (“22-31 days”). A cutoff of ≥2 was used to classify individuals with sleep disturbances. The internal consistency of the German translation of the JSS in the current sample was good with Cronbach’s alpha of .92.

Statistics All statistical analyses were conducted using the statistical package PASW 19.0 for Windows. Participants with and without RLS were compared using parametric tests for continuous variables and chi-square tests for categorical variables, as appropriate. Binary logistic regression analyses were conducted with RLS diagnosis as the dependent variable and the presence/absence of adult ADHD as the main independent variable. Given possible mediating effects of variables that were significantly related to the dependent variable (RLS diagnosis) as well as to the main independent variable (adult ADHD), we carried out additional regression analyses adjusting for demographics, BMI, depression and anxiety, and sleep disturbances. An alpha level of .05 was applied for all tests.

Results Study Sample Table 1 presents the detailed description of the total study sample and the distribution by RLS category. With regard to educational level, 15.8% of the total sample had finished high school or attained education beyond high school. The screening for current depression and anxiety using PHQ-4 revealed positive results in 5.6% of the total sample. In accordance with an earlier publication (de Zwaan et al., 2012) which was based on the same sample, the prevalence of adult ADHD was 4.7% (n = 76) in the total sample. Thirteen percent of the total sample reported sleep disturbances.

RLS and Correlates The prevalence of RLS was 3.2% (n = 52). With regard to educational level, only one person in the RLS group (1.9%) had finished high school or attained education beyond high school compared with 16.3% among those without RLS. As can be seen in Table 1, individuals with RLS were older, more

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Table 1.  Sociodemographic Characteristics, BMI, Presence of Adult ADHD, and Depression/Anxiety in the Total Sample and by RLS Category. RLS

Variables Age   Gender  Female   Marital status  Married   Never married  Divorced  Widowed Unemployed   Urbanicity  Urban  Rural BMI categories  Under-/normal-weight  Overweight  Obesity Depression/anxietya   Sleep disturbanceb   Adult ADHDc  

Total sample (N = 1,632)

Absent (n = 1,580)

Present (n = 52)

Statistics

M (SD)

M (SD)

M (SD)

t test

43.2 (12.7)

43.0 (12.7)

51.1 (11.5)

t = −4.55, df = 1,630, p< .001

n (%)

n (%)

n (%)

χ2 test

875 (53.6)

849 (53.7)

26 (50.0)

χ2 = .282, df = 1 n.s.

880 (53.9) 451 (27.0) 239 (14.6) 62 (3.80) 141 (8.6)

853 (54.0) 444 (28.1) 229 (14.5) 54 (3.4) 134 (8.5)

27 (51.9) 7 (13.5) 10 (19.2) 8 (15.4) 7 (13.5)

χ2 = 23.693, df = 3 p< .001     χ2 = 1.582, df = 1 n.s.

1,443 (88.4) 189 (11.6)

1,403 (88.8) 177 (11.2)

40 (76.9) 12 (23.1)

χ2 = 6.932, df = 1 p< .01

897 (55.0) 560 (34.3) 175 (10.7) 92 (5.6)

880 (55.7) 540 (34.2) 160 (10.1) 80 (5.1)

17 (32.7) 20 (38.5) 15 (28.5) 12 (23.1)

217 (13.3)

187 (11.9)

30 (57.7)

76 (4.6)

67 (4.2)

9 (17.3)

χ2 = 21.568, df = 2 p< .001   χ2 = 30.710, df = 1 p< .001 χ2 = 91.669, df = 1 p< .001 χ2 = 19.361, df = 1 p< .001

Note. BMI = body mass index; RLS = restless legs syndrome; n.s. = not significant. a Patient Health Questionnaire–4 total scores ≥6. b Jenkins Sleep Scale total score ≥2 c Short version of the Wender Utah Rating (total score ≥30) and the ADHD self-rating scale (total score ≥15).

often obese, and more often living in a rural area. No significant differences were found for gender and employment status. Positive screening results for depression and anxiety were significantly more prevalent in individuals with RLS.

Association Between RLS and Adult ADHD As reported in Table 1, participants with RLS were more likely to suffer from adult ADHD than those without RLS. Vice versa, RLS was more prevalent among individuals with adult ADHD (11.8%, n = 9) than among those without ADHD (2.8%, n = 43). Table 2 summarizes the results of regression analyses with RLS as the dependent variable. In the crude logistic regression, adult ADHD was strongly associated with statistically significant increases in the odds of having RLS

(odds ratio [OR] = 4.73, 95% confidence interval [CI] = [2.21, 10.09]). The association remained considerable when adjusting for demographics (age, marital status, urbanicity). Also, the results did not change substantially after additional adjusting for BMI, and for the presence of anxiety and depression. However, the association between adult ADHD and RLS was rendered insignificant after adjusting not only for demographics, BMI, and anxiety and depression but also for the presence of sleep disturbances (OR = 2.02, 95% CI = [0.82, 4.96], p = .13).

Discussion To date, the relationship between RLS and adult ADHD has been studied mostly in clinical samples. The present work is the first community-based study to examine the association

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Roy et al. Table 2.  Summary of Binary Logistic Regression Models Concerning the Association Between RLS and Adult ADHD (N = 1,632). RLS (present/absent) odds ratio (95% CI) Unadjusted model   No ADHD 1.0   Adult ADHD 4.73 [2.21, 10.09]** Adjusted for demographicsa   No ADHD 1.0   Adult ADHD 4.72 [2.02, 11.04]** Adjusted for demographics and BMI   No ADHD 1.0   Adult ADHD 4.57 [1.96, 10.44]* Adjusted for demographics and depression/anxietyb   No ADHD 1.0   Adult ADHD 3.09 [1.24, 7.68]* Adjusted for demographics, BMI, and depression/anxietyb   No ADHD 1.0   Adult ADHD 3.18 [1.29, 7.63]* Adjusted for demographics and sleep disturbancec   No ADHD 1.0   Adult ADHD 2.27 [0.93, 5.54] Adjusted for demographics, BMI, depression/anxiety,b and sleep disturbancec   No ADHD 1.0   Adult ADHD 2.02 [0.82, 4.96] Note. RLS = restless legs syndrome; BMI = body mass index; CI = confidence interval. a Age, marital status, rural/urban residency. b Patient Health Questionnaire–4 total scores ≥6. c Jenkins Sleep Scale total score ≥2. *p< .05. **p< .001.

between RLS and ADHD in adults conducted in a large representative European sample. In accordance with our expectations, the findings indeed indicate that adult ADHD appears to be significantly associated with RLS. The association did not become substantially attenuated after adjusting for potential confounding factors such as age, depression and anxiety, and obesity. Thus, this part of the results resembles the findings of earlier studies that consistently found a strong link between RLS and adult ADHD (Schredl et al., 2007; Yoon et al., 2012; Zak et al., 2009). There are several ways to interpret these findings. First of all, the link between RLS and ADHD may suggest a true comorbidity, which might be explained by shared psychophysiology. Several studies have shown that dopaminergic deficiency may play a role in both conditions (Cervenka et al., 2006; Philipsen et al., 2006; Trenkwalder, Paulus, & Walters, 2005; Wagner et al., 2004). Furthermore, relative iron deficiency has been found to be relevant in the pathophysiology of both RLS and ADHD (Cortese, Azoulay, et al., 2012; Cortese, Angriman, Lecendreux, & Konofal, 2012; M. A. Picchietti & Picchietti, 2010; Yeh, Walters, & Tsuang,

2012). Some studies showed that children with ADHD and RLS were at high risk of iron deficiency (Cortese, Angriman, et al., 2012). Another plausible explanation concerns poor quality of sleep in people with RLS, in particular, sleep disruptions and insomnia, that might lead to ADHD-like symptoms or exacerbate the symptoms of ADHD such as inattention, concentration deficits, and impaired impulse-control (Wagner et al., 2004; Yoon et al., 2012; Zak et al., 2009). Although the cross-sectional nature of our data precludes causal conclusions, the second part of our findings indeed supports this hypothesis, given that the aforementioned association between RLS and adult ADHD did no longer hold true after controlling for sleep disturbances. Considering that poor quality of sleep is known to be linked to RLS (Allen et al., 2003; Ohayon et al., 2012) as well as to ADHD (Konofal et al., 2010; Schredl et al., 2007; Yoon et al., 2012), one may assume that sleep disturbances mediate the relationship between RLS and adult ADHD (Baron & Kenny, 1986). Sleep impairment caused by RLS could mimic ADHD symptoms such as inner restlessness and inability to relax that could erroneously be diagnosed as adult ADHD. The presence of these symptoms, in turn, could worsen sleep disturbances. However, a false diagnosis of RLS can appear due to incorrect interpretations of ADHD symptoms such as restlessness. However, Wagner et al. (2004) reported that more RLS patients (26%) than insomnia patients (6%) had ADHD symptoms, indicating that insomnia is not the only link between RLS and ADHD. Nevertheless, the findings may suggest implications for clinical routine and treatment. Considering that ADHD symptoms are associated with RLS and that this relationship might be partly mediated by poor quality of sleep, as mentioned above, it is reasonable to suggest that the diagnosis and the understanding of this relationship can improve the level of medical care of patients suffering from all three conditions. At the same time, it appears worth mentioning that England et al. (2011) in their double-blind, placebo-controlled trial in 29 children indeed found that L-Dopa significantly improved RLS but not ADHD. However, caution regarding this result is warranted due to the relatively small sample size and baseline group differences in severity of ADHD. It is also important to pay attention to the hypothesis of Angriman et al. (2013), suggesting that RLS comorbid with ADHD may be associated with a higher risk for cardiovascular disease because of an imbalance in the activity of the autonomic nervous system. As medication for ADHD can have side effects on the cardiovascular system, for example, elevation in heart rate and blood pressure, the authors recommend to effectively treat RLS before starting treatment for ADHD. However, only few randomized-controlled trials have investigated treatment of ADHD in combination with RLS, further investigation is needed (Cortese et al., 2013).

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The use of a large, population-based sample is a notable strength of the present study. Shortcomings include the use of self-ratings instead of clinical interviews to estimate the prevalence of RLS, adult ADHD, sleep disturbances, and depression and anxiety. However, RLS is a clinical diagnosis without availability of diagnostic tests or a specific laboratory marker (Chokroverty, 2014), and the assessment methods used in this study have been validated and used in several clinical and community-based samples (Berger et al., 2004; de Zwaan et al., 2012; Happe, Vennemann, Evers, & Berger, 2008; Philipsen et al., 2008). Nevertheless, the diagnostic criteria have been updated in the year 2012. The RLS criteria used in our survey (see “Methods” section) remained the same; however, an additional exclusion criterion was added (“The occurrence is not solely accounted for as symptom primary to another medical or behavior condition”; Allen, 2014). As the study was conducted in 2009, it does not include this new item but meets all the other diagnostic criteria. It is therefore not possible to distinguish between idiopathic and symptomatic RLS in our sample. In terms of valid ADHD diagnosis, the ability of adults to recall ADHD symptoms in childhood remains questionable (Mannuzza, Klein, Klein, Bessler, & Shrout, 2002). Therefore, even though RLS seems to be more prevalent in older individuals (Ohayon et al., 2012), we decided not to analyze the data of respondents whose age was above 64 years for the present study to minimize the risk of incorrect ADHD diagnoses. In these individuals, there would have been a higher risk of insecurity of childhood ADHD diagnoses on one hand and of interferences in the case of mild cognitive impairment on the other hand. Another limitation concerns the lack of information on medication that potentially could have influenced the observed associations (Philipsen et al., 2006) as well as other psychiatric and somatic disorders. Especially, cardiovascular disease was not evaluated in our study as it is known to be associated with RLS (Becker & Novak, 2014). Also, based on our data, we were not able to discriminate between idiopathic and symptomatic RLS. Finally we have to point out that height and weight data were self-reported. However, Kuczmarski, Kuczmarski, and Najjar (2001) showed in a large representative U.S. sample that especially in the age group below 60 years, self-reported height and weight data are valid and can be used. In summary, our results confirm that ADHD symptoms in the adult population are linked to RLS in a representative German community sample. For clinical implications, clinicians should be aware about the proposed associations and address them as appropriate. An area of further research relates to the treatment of comorbid ADHD and RLS. Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.

References Allen, R. P. (2014). Restless legs syndrome/Willis Ekbom disease: Evaluation and treatment. International Review of Psychiatry, 26, 248-262. doi:10.3109/09540261.2014.904279 Allen, R. P., Picchietti, D., Hening, W. A., Trenkwalder, C., Walters, A. S., Montplaisi, J., . . . International Restless Legs Syndrome Study Group. (2003). Restless legs syndrome: Diagnostic criteria, special considerations, and epidemiology: A report from the restless legs syndrome diagnosis and epidemiology workshop at the national institutes of health. Sleep Medicine, 4, 101-119. American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders (4th ed.). Washington, DC: Author. Angriman, M., Bruni, O., & Cortese, S. (2013). Does restless legs syndrome increase cardiovascular risk in attention-deficit/hyperactivity disorder? Medical Hypotheses, 80, 39-42. doi:10.1016/j.mehy.2012.10.004 Baron, R. M., & Kenny, D. A. (1986). The moderator-mediator variable distinction in social psychological research: Conceptual, strategic, and statistical considerations. Journal of Personality and Social Psychology, 51, 1173-1182. Becker, P. M., & Novak, M. (2014). Diagnosis, comorbidities, and management of restless legs syndrome. Current Medical Research & Opinion, 30, 1441-1460. doi:10.1185/03007995 .2014.918029 Berger, K., Luedemann, J., Trenkwalder, C., John, U., & Kessler, C. (2004). Sex and the risk of restless legs syndrome in the general population. Archives of Internal Medicine, 164, 196202. doi:10.1001/archinte.164.2.196 Cervenka, S., Palhagen, S. E., Comley, R. A., Panagiotidis, G., Cselenyi, Z., Matthews, J. C., . . .Farde, L. (2006). Support for dopaminergic hypoactivity in restless legs syndrome: A PET study on D2-receptor binding. Brain: A Journal of Neurology, 129(Pt. 8), 2017-2028. doi:10.1093/brain/awl163 Chokroverty, S. (2014). Editor’s perspective: RLS/WED diagnostic criteria: An unfortunate conundrum in search of rectification. Sleep Medicine, 15, 845. doi:10.1016/j.sleep.2014.07.004 Cortese, S., Angriman, M., Lecendreux, M., & Konofal, E. (2012). Iron and attention deficit/hyperactivity disorder: What is the empirical evidence so far? A systematic review of the literature. Expert Review of Neurotherapeutics, 12, 1227-1240. doi:10.1586/ern.12.116 Cortese, S., Angriman, M., Maffeis, C., Isnard, P., Konofal, E., Lecendreux, M., . . .Mouren, M. C. (2008). Attention-deficit/ hyperactivity disorder (ADHD) and obesity: A systematic review of the literature. Critical Reviews in Food Science and Nutrition, 48, 524-537. doi:10.1080/10408390701540124; 10.1080/10408390701540124 Cortese, S., Azoulay, R., Castellanos, F. X., Chalard, F., Lecendreux, M., Chechin, D., . . .Konofal, E. (2012). Brain iron levels in attention-deficit/hyperactivity disorder: A pilot MRI study. The World Journal of Biological Psychiatry: The Official Journal of the World Federation of Societies of

Downloaded from jad.sagepub.com at Apollo Group - UOP on January 28, 2015

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Roy et al. Biological Psychiatry, 13, 223-231. doi:10.3109/15622975.2 011.570376 Cortese, S., Brown, T. E., Corkum, P., Gruber, R., O’Brien, L. M., Stein, M., . . .Owens, J. (2013). Assessment and management of sleep problems in youths with attention-deficit/ hyperactivity disorder. Journal of the American Academy of Child & Adolescent Psychiatry, 52, 784-796. doi:10.1016/j. jaac.2013.06.001 Cortese, S., Konofal, E., Lecendreux, M., Arnulf, I., Mouren, M. C., Darra, F., & Dalla Bernardina, B. (2005). Restless legs syndrome and attention-deficit/hyperactivity disorder: A review of the literature. Sleep, 28, 1007-1013. Cortese, S., Lecendreux, M., Mouren, M. C., & Konofal, E. (2006). ADHD and insomnia. Journal of the American Academy of Child & Adolescent Psychiatry, 45, 384-385. doi:10.1097/01. chi.0000199577.12145.bc Cumyn, L., French, L., & Hechtman, L. (2009). Comorbidity in adults with attention-deficit hyperactivity disorder. Canadian Journal of Psychiatry/Revue Canadienne De Psychiatrie, 54, 673-683. de Zwaan, M., Gruss, B., Muller, A., Graap, H., Martin, A., Glaesmer, H., . . . Philipsen, A. (2012). The estimated prevalence and correlates of adult ADHD in a German community sample. European Archives of Psychiatry & Clinical Neuroscience, 262, 79-86. doi:10.1007/s00406-011-0211-9 de Zwaan, M., Gruss, B., Muller, A., Philipsen, A., Graap, H., Martin, A., . . . Hilbert, A. (2011). Association between obesity and adult attention-deficit/hyperactivity disorder in a German community-based sample. Obesity Facts, 4, 204-211. doi:10.1159/000329565 England, S. J., Picchietti, D. L., Couvadelli, B. V., Fisher, B. C., Siddiqui, F., Wagner, M. L., . . .Walters, A. S. (2011). L-dopa improves restless legs syndrome and periodic limb movements in sleep but not attention-deficit-hyperactivity disorder in a double-blind trial in children. Sleep Medicine, 12, 471477. doi:10.1016/j.sleep.2011.01.008 Gamaldo, C. E., Benbrook, A. R., Allen, R. P., Scott, J. A., Henning, W. A., & Earley, C. J. (2007). Childhood and adult factors associated with restless legs syndrome (RLS) diagnosis. Sleep Medicine, 8, 716-722. doi:10.1016/j.sleep.2006.09.004 Gao, X., Schwarzschild, M. A., Wang, H., & Ascherio, A. (2009). Obesity and restless legs syndrome in men and women. Neurology, 72, 1255-1261. doi:10.1212/01. wnl.0000345673.35676.1c Gruss, B., Mueller, A., Horbach, T., Martin, A., & de Zwaan, M. (2012). Attention-deficit/hyperactivity disorder in a prebariatric surgery sample. European Eating Disorders Review: The Journal of the Eating Disorders Association, 20, e103-e107. doi:10.1002/erv.1128 Happe, S., Vennemann, M., Evers, S., & Berger, K. (2008). Treatment wish of individuals with known and unknown restless legs syndrome in the community. Journal of Neurology, 255, 1365-1371. doi:10.1007/s00415-008-0922-7 Hogl, B., Kiechl, S., Willeit, J., Saletu, M., Frauscher, B., Seppi, K., . . .Poewe, W. (2005). Restless legs syndrome: A community-based study of prevalence, severity, and risk factors. Neurology, 64, 1920-1924. doi:10.1212/01. WNL.0000163996.64461.A3

Hornyak, M. (2010). Depressive disorders in restless legs syndrome: Epidemiology, pathophysiology and management. CNS Drugs, 24, 89-98. doi:10.2165/11317500-000000000-00000 Jenkins, C. D., Stanton, B. A., Niemcryk, S. J., & Rose, R. M. (1988). A scale for the estimation of sleep problems in clinical research. Journal of Clinical Epidemiology, 41, 313-321. Konofal, E., Lecendreux, M., & Cortese, S. (2010). Sleep and ADHD. Sleep Medicine, 11, 652-658. doi:10.1016/j. sleep.2010.02.012 Kroenke, K., Spitzer, R. L., Williams, J. B., & Löwe, B. (2009). An ultra-brief screening scale for anxiety and depression: The PHQ-4. Psychosomatics, 50, 613-621. doi:10.1176/appi. psy.50.6.613 Kuczmarski, M. F., Kuczmarski, R. J., & Najjar, M. (2001). Effects of age on validity of self-reported height, weight, and body mass index: Findings from the third national health and nutrition examination survey, 1988-1994. Journal of the American Dietetic Association, 101, 28-34; quiz 35-36. doi:S0002-8223(01)00008-6 [pii] Lewin, D. S., & Di Pinto, M. (2004). Sleep disorders and ADHD: Shared and common phenotypes. Sleep, 27, 188-189. Löwe, B., Wahl, I., Rose, M., Spitzer, C., Glaesmer, H., Wingenfeld, K., . . .Brahler, E. (2010). A 4-item measure of depression and anxiety: Validation and standardization of the patient health questionnaire-4 (PHQ-4) in the general population. Journal of Affective Disorders, 122, 86-95.doi:10.1016/j. jad.2009.06.019 Mannuzza, S., Klein, R. G., Klein, D. F., Bessler, A., & Shrout, P. (2002). Accuracy of adult recall of childhood attention deficit hyperactivity disorder. The American Journal of Psychiatry, 159, 1882-1888. Ohayon, M. M., O’Hara, R., & Vitiello, M. V. (2012). Epidemiology of restless legs syndrome: A synthesis of the literature. Sleep Medicine Reviews, 16, 283-295. doi:10.1016/j. smrv.2011.05.002 Ohayon, M. M., & Roth, T. (2002). Prevalence of restless legs syndrome and periodic limb movement disorder in the general population. Journal of Psychosomatic Research, 53, 547-554. Ondo, W., & Jankovic, J. (1996). Restless legs syndrome: Clinicoetiologic correlates. Neurology, 47, 1435-1441. Philipsen, A., Feige, B., Hesslinger, B., Ebert, D., Carl, C., Hornyak, M., . . .Riemann, D. (2005). Sleep in adults with attention-deficit/hyperactivity disorder: A controlled polysomnographic study including spectral analysis of the sleep EEG. Sleep, 28, 877-884. Philipsen, A., Hornyak, M., & Riemann, D. (2006). Sleep and sleep disorders in adults with attention deficit/hyperactivity disorder. Sleep Medicine Reviews, 10, 399-405. doi:10.1016/j. smrv.2006.05.002 Philipsen, A., Limberger, M. F., Lieb, K., Feige, B., Kleindienst, N., Ebner-Priemer, U., . . .Bohus, M. (2008). Attentiondeficit hyperactivity disorder as a potentially aggravating factor in borderline personality disorder. The British Journal of Psychiatry: The Journal of Mental Science, 192, 118-123. doi:10.1192/bjp.bp.107.035782 Phillips, B., Young, T., Finn, L., Asher, K., Hening, W. A., & Purvis, C. (2000). Epidemiology of restless legs symptoms in adults. Archives of Internal Medicine, 160, 2137-2141.

Downloaded from jad.sagepub.com at Apollo Group - UOP on January 28, 2015

8

Journal of Attention Disorders 

Picchietti, D., Allen, R. P., Walters, A. S., Davidson, J. E., Myers, A., & Ferini-Strambi, L. (2007). Restless legs syndrome: Prevalence and impact in children and adolescents—The peds REST study. Pediatrics, 120, 253-266. doi:10.1542/ peds.2006-2767 Picchietti, M. A., & Picchietti, D. L. (2010). Advances in pediatric restless legs syndrome: Iron, genetics, diagnosis and treatment. Sleep Medicine, 11, 643-651. doi:10.1016/j. sleep.2009.11.014 Retz-Junginger, P., Retz, W., Blocher, D., Stieglitz, R. D., Georg, T., Supprian, T., . . .Rosler, M. (2003). Reliability and validity of the wender-utah-rating-scale short form. retrospective assessment of symptoms for attention deficit/ hyperactivity disorder/Reliabilitat und Validitat der WenderUtah-Rating-Scale-Kurzform. Retrospektive Erfassung von Symptomen aus dem Spektrum der Aufmerksamkeitsdefizit/ Hyperaktivitatsstorung. Der Nervenarzt, 74, 987-993. doi:10.1007/s00115-002-1447-4 Retz-Junginger, P., Retz, W., Blocher, D., Weijers, H. G., Trott, G. E., Wender, P. H., & Rossler, M. (2002). Wender utah rating scale. The short-version for the assessment of the attentiondeficit hyperactivity disorder in adults/Wender Utah Rating Scale (WURS-k) Die deutsche Kurzform zur retrospektiven Erfassung des hyperkinetischen Syndroms bei Erwachsenen. Der Nervenarzt, 73, 830-838. doi:10.1007/s00115-0011215-x Rösler, M., Retz, W., Retz-Junginger, P., Thome, J., Supprian, T., Nissen, T., . . .Trott, G. E. (2004). Tools for the diagnosis of attention-deficit/hyperactivity disorder in adults. Self-rating behaviour questionnaire and diagnostic checklist/Instrumente zur Diagnostik der Aufmerksamkeitsdefizit-/Hyperaktivitatsstorung (ADHS) im ErwachsenenalterSelbstbeurteilungsskala (ADHS-SB) und Diagnosecheckliste (ADHS-DC). Der Nervenarzt, 75, 888895. doi:10.1007/s00115-003-1622-2 Rösler, M., Retz-Junginger, P., Retz, W., & Stieglitz, R. (2008). Homburger ADHS-skalen für erwachsene (HASE): Untersuchungsverfahren zur syndromalen und kategorialen diagnostik der aufmerksamkeitsdefizit-/ hyperaktivitätsstörung (ADHS) im erwachsenenalter [Homburger ADHD-Scales for Adults (HASE): Investigation procedure for syndromal and categorial diagnostics of adult ADHD]. Göttingen, Germany: Hogrefe. Salo, P., Oksanen, T., Sivertsen, B., Hall, M., Pentti, J., Virtanen, M., . . .Kivimaki, M. (2010). Sleep disturbances as a predictor of cause-specific work disability and delayed return to work. Sleep, 33, 1323-1331. Schredl, M., Alm, B., & Sobanski, E. (2007). Sleep quality in adult patients with attention deficit hyperactivity disorder (ADHD). European Archives of Psychiatry & Clinical Neuroscience, 257, 164-168. doi:10.1007/s00406-0060703-1 Sobanski, E., Bruggemann, D., Alm, B., Kern, S., Deschner, M., Schubert, T., . . .Rietschel, M. (2007). Psychiatric comorbidity and functional impairment in a clinically referred sample of adults with attention-deficit/hyperactivity disorder (ADHD). European Archives of Psychiatry & Clinical Neuroscience, 257, 371-377. doi:10.1007/s00406-007-0712-8

Steinlechner, S., Bruggemann, N., Sobottka, V., Benthien, A., Behn, B., Klein, C., . . .Lencer, R. (2011). Restless legs syndrome as a possible predictor for psychiatric disorders in parents of children with ADHD. European Archives of Psychiatry & Clinical Neuroscience, 261, 285-291. doi:10.1007/s00406010-0140-z Symvoulakis, E., Anyfantakis, D., & Lionis, C. (2010). Restless legs syndrome: Literature review. Sao Paulo Medical Journal/ Revista Paulista De Medicina, 128, 167-170. Trenkwalder, C., Paulus, W., & Walters, A. S. (2005). The restless legs syndrome. Lancet Neurology, 4, 465-475. doi:10.1016/ S1474-4422(05)70139-3 Wagner, M. L., Walters, A. S., & Fisher, B. C. (2004). Symptoms of attention-deficit/hyperactivity disorder in adults with restless legs syndrome. Sleep, 27, 1499-1504. Walters, A. S. (1995). Toward a better definition of the restless legs syndrome. The international restless legs syndrome study group. Movement Disorders: Official Journal of the Movement Disorder Society, 10, 634-642.doi:10.1002/mds.870100517 Walters, A. S., Silvestri, R., Zucconi, M., Chandrashekariah, R., & Konofal, E. (2008). Review of the possible relationship and hypothetical links between attention deficit hyperactivity disorder (ADHD) and the simple sleep related movement disorders, parasomnias, hypersomnias, and circadian rhythm disorders. Journal of Clinical Sleep Medicine: Official Publication of the American Academy of Sleep Medicine, 4, 591-600. Yeh, P., Walters, A. S., & Tsuang, J. W. (2012). Restless legs syndrome: A comprehensive overview on its epidemiology, risk factors, and treatment. Sleep & Breathing/Schlaf & Atmung, 16, 987-1007. doi:10.1007/s11325-011-0606-x Yoon, S. Y., Jain, U., & Shapiro, C. (2012). Sleep in attentiondeficit/hyperactivity disorder in children and adults: Past, present, and future. Sleep Medicine Reviews, 16, 371-388. doi:10.1016/j.smrv.2011.07.001 Zak, R., Fisher, B., Couvadelli, B. V., Moss, N. M., & Walters, A. S. (2009). Preliminary study of the prevalence of restless legs syndrome in adults with attention deficit hyperactivity disorder. Perceptual & Motor Skills, 108, 759-763.

Author Biographies Mandy Roy, MD, is psychiatrist and psychotherapist at the Department of Psychiatry, Hannover Medical School, Germany. Her research interest includes ADHD and autism spectrum disorders in adulthood as well as functional imaging. Martina de Zwaan, MD, professor, is specialist for psychosomatic medicine, psychiatrist and psychotherapist and director of the Department of Psychosomatic Medicine and Psychotherapy, Hannover Medical School, Germany. Her research interests include ADHD, eating disorders, psychosocial aspects of bariatric surgery, and psychotherapy research. Inka Tuin, MD, is specialist for neurology, psychiatrist and psychotherapist and somnologist at the Department of Psychosomatic Medicine and Psychotherapy, University of Mainz, Germany. Her research interests include sleep movement disorders (restless legs syndrome, bruxism) and chronic facial pain.

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Roy et al. Alexandra Philipsen, professor, is psychiatrist and psychotherapist at the Faculty of Medicine and Health Sciences, Carl von Ossietzky University Oldenburg, Germany. Her main research interests include ADHD, borderline personality disorder, nonpharmacological treatment of ADHD and brain imaging. Elmar Brähler, professor, is a mathematician and was director of the Department of Medical Psychology and Medical Sociology, University of Leipzig, Germany. His research interests included

psychological diagnostics, coping with chronic diseases as well as aspects of reproduction medicine and unemployment. Astrid Müller, MD, PhD, is head psychologist at the Department of Psychosomatic Medicine and Psychotherapy, Hannover Medical School, Germany. Her research interests include ADHD, impulse-control disorders, behavioral addictions as well as psychosocial aspects, neurocognitive functions and temperament in extreme obesity.

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