In this cross-sectional study, we found that mothers who reported having a child with ADHD had a modestly increased risk of having RLS, relative to those who did not report this condition. Our results are consistent with previous studies which reported co-occurrence of RLS and ADHD (1
). For example, in a study including adult patients (n=171, mean age 61–63 y) with RLS, insomnia and healthy controls, ADHD, as assessed by DSM-IV ADHD scores, were found in 26% of RLS patients, relative to 6% of insomnia patients, and 5% of controls (3
). In a large-scaled cross-sectional study including 10523 children and adolescents high prevalence of ADHD/ADD was found among 206 children or adolescents who met the diagnostic criteria for definite RLS (14.8% among 8 to 11-year-olders and 17.6% among 12 to 17-year-olders) (11
). In a study including 18 children and adolescents with RLS, 13 of them were found to have ADHD and 10 with both ADHD and a family history of RLS (12
). However, the high proportion of ADHD found in this study could be partly due to the investigators’ initial interest in researching RLS patients who were referred for ADHD (12
). It is worth noting that, unlike previous published studies, the current study is the first to examine the connections between RLS and ADHD across generations.
A possible interpretation for the observed association between having a child with ADHD and risk of RLS is that these two conditions share common genetic determinants. BTBD9, which has been identified by two recent GWASs to be associated with risk of RLS (6
), could be a potential candidate (5
). Interestingly, the RLS risk allele of BTBD9 is associated with decreased serum ferritin concentration (7
). Iron deficiency has been suggested as a risk factor of RLS (13
) and ADHD (14
). Other potential candidate genes include the protein tyrosine phosphatase gene(16
) and nitric oxide synthase 1 (18
), which have also been found to be associated with risk of both ADHD and RLS. Also of interest is the observation that both ADHD and RLS have been reported in patients with Tourette’s syndrome.(1
). In a recent case-control study of three RLS-related BTBD9 single-nucleotide polymorphisms were found to be significantly associated with Tourettes’s syndrome risk.(20
It is also possible that as sleep deprivation or depression is caused by RLS, women with RLS may exaggerate the ADHD-like behaviors in their child. However, we adjusted for use of antidepressants in our main analyses. Further adjustment for anxiety score, as well as exclusion of women reporting use of antidepressants also did not materially change the significance of the observed association.
A limitation of the current study is that we did not collect ADHD status among nurses. Because the heritability of ADHD has been suggested to be high (~60–80%) (5
), it is likely that nurses who reported having a child with ADHD were also at high risk of having ADHD. Similar concerns are raised because we did not assess for the presence or absence of RLS in the ADHD children and other family members. Some misclassification in RLS due to some RLS-like symptoms is also likely. Another limitation is that assessment of ADHD in offspring relied on self-reports, and some degree of misdiagnosis is thus inevitable. However, the validation study suggests that the accuracy is rather high; further, this is a sample of medically trained nurses who have been shown to provide reliable and valid information on diseases. Limitations of the current study also include that lack of information on subtype of ADHD, date of ADHD onset, other clinical information (e.g., iron deficiency), and birth order among offspring, as well as the number of affected children in each family.
In conclusion, in this large investigation we found that mothers of children with ADHD have an increased risk of RLS. Because of potential limitations as described above, our study should be considered preliminary. Nevertheless, these results confirm and extend previous observations and are consistent with the existence of a shared genetic susceptibility between RLS and ADHD.