Overweight in family members of probands with ADHD

Is there a relationship between attention-deficit/hyperactivity disorder (ADHD) and being overweight? This has been the central question for many small- and large-scale studies during the last 2 decades. Two recent meta-analyses concluded that people with ADHD have a 20–30% increased chance of being overweight compared to population prevalence rates [1, 2]. Inconsistent conclusions were drawn regarding gender effects [1, 2]. Vice versa, it has also been shown that overweight individuals—compared to individuals with a healthy weight—are more likely to show ADHD symptoms [3‐5].

Various mechanisms have been proposed to explain the association between ADHD and overweight. ADHD may causally lead to overweight through impulsive (binge) eating [6] since ADHD is often characterized by emotional lability, impulsivity, and disturbances in sleep and circadian rhythm [7, 8]. There is no direct evidence for this hypothesis, but there is a substantial amount of indirect evidence. The prevalence of binge eating symptoms and bulimia nervosa is higher in patients with ADHD [9]. Similarly, patients with bulimia nervosa have an increased chance of having (a childhood history of) ADHD and executive control problems [10‐12]. Alternatively, instead of a causal association between ADHD and overweight, shared etiologies between ADHD and overweight may be key to understanding the association between both. Currently, to the best of our knowledge, one twin and sibling study has directly tested the contribution of shared genetic and environmental factors for both phenotypes in young and older adulthood [13]. They found a significant role for unique environmental influences explaining the association between both phenotypes in males and genetic influences contributing to the association between both phenotypes in females. Similarly, another study also suggested that the association between ADHD and binge eating in females was largely explained by shared genetic risk factors [14], suggesting the mechanisms underlying the association between ADHD and overweight may be different in males and females. Several molecular genetic studies have reported common candidate genes for ADHD and increased BMI [15‐17]. In addition, a large-scale genetic correlation between both phenotypes was reported based on genome-wide association studies of common genetic variants, but potential sex moderating effects were not reported [18]. Apart from a shared genetic background, both phenotypes also show very similar relationships with adverse environmental factors such as low socio-economic status, parental psychopathology, and poor nutritional and exercise habits [19‐23]. A recent report even argued that the link between ADHD symptoms and increased body weight could be completely explained by cumulative psychosocial risks, and highlighted the importance of chronic stress as a trigger for both conditions [19]. In a recent comprehensive review on potential mechanism explaining the association between ADHD and overweight [24], including genetic factors, fetal programming, executive dysfunctions, psychosocial stress, factors directly related to energy balance, and sleep patterns alterations, it was concluded that physical activity and eating patterns as possible and most direct causes of weight gain do not seem to fully explain the link and need to be integrated in a broader biopsychosocial model. It was proposed that ADHD and obesity might have a common neurocognitive phenotype, characterized by deficits in hot executive functions, associated with impulsivity and difficulties in postponing gratification [24]. Fetal programming is proposed to be an important element in this model, with environmental agents such as maternal stress, maternal smoking, and drinking alcohol during pregnancy disrupting the development of executive functions.

To test this model, this study employs a within-family design to examine mechanisms underlying the association between ADHD and being overweight in ADHD-affected and -unaffected family members taking into account age, gender, and medication use since these have been reported as moderating factors [25‐28]. A family-based study design including unaffected family members of patients with ADHD provides unique opportunities. It allows to investigate whether overweight in ADHD is associated with the presence of ADHD or with shared familial factors. If the association between ADHD and overweight is indeed primarily linked to deficits in hot executive functions, characterized by impulsivity and difficulties in postponing gratification, it is expected that overweight will be primarily present in family members meeting criteria for ADHD. However, if the association between ADHD and overweight is primarily explained by factors shared by family members with and without ADHD, a similar increased prevalence of being overweight in family members affected and unaffected by ADHD is expected compared to population prevalence rates. In addition, the predictive effect of parental BMI on child BMI is expected to be larger than the predictive effect of parental ADHD on child BMI. Remarkably and to the best of our knowledge, only one prior study addressed this issue in a family design, albeit indirectly [29]. In a large population-based sample (N = 11,159), the association between children’s (6–17 years) ADHD symptoms and body mass index (BMI) status was strongly attenuated when parental BMI was accounted for [29]. This may indicate that the association between ADHD symptoms and overweight/obesity is due to confounding by family background. However, parental ADHD symptoms were not taken into account, preventing a direct comparison of the effects of parental BMI and parental ADHD status on offspring weight status. One previous study included unaffected siblings for studying the relationship between overweight and ADHD within families [5]. However, parental overweight and ADHD symptoms were not included in this study.

Demographics of the sample are shown in Table 1. Compared to the unaffected siblings’ assessments, ADHD-affected youth were younger than their unaffected siblings, had lower IQ scores, were more likely male and had—as expected—higher ADHD symptom scores. Parental variables, except for maternal age, were similar for both groups of youth (Table 1). Point prevalence rates of overweight uncorrected for age and sex were 17.6% (ADHD-affected youth), 22.0% (unaffected siblings), 60.4% (mothers) and 72.3% (fathers).

In relation to the main objective whether or not ADHD is associated with overweight within families, the first step (default youth model) showed no main effect of ADHD status on overweight status (OR 0.92, 95% CI 0.78–1.09), i.e., youth with and without ADHD were equally likely to be overweight. In the second step (extended youth model), we found a small ADHD status by age interaction effect such that the risk for being overweight increased with age in youth with ADHD but not in unaffected youth (OR 1.04, 95% CI 1.01–1.07); however, this effect did not survive correction for multiple testing. No other significant or near-significant two-level interactions among predictors were found in the extended model.

In the third step (parental youth model), adding parental variables to the model predicting youth overweight status did not change the predictive value of the default model variables (ADHD diagnosis, gender, age, age², and IQ). Both maternal and paternal overweight predicted overweight in their offspring (mothers OR 1.40; 95% CI 1.14–1.73, fathers OR 1.83; 95% CI 1.41–2.36) (Table 2). Maternal education was predictive of offspring overweight (OR 1.05; 95% CI 1.00–1.10), but this effect did not survive correction for multiple testing. Parental age and ADHD above cut-off were not predictive of being overweight in offspring. In the last step (affected youth medication model), the use of psychostimulants, antipsychotics, or melatonin did not change the predictive value of the default model variables and was not predictive of being overweight in ADHD-affected youth (OR 0.98, 95% CI 0.76–1.26; OR 0.81, 95% CI 0.49–1.34; OR 0.74, 95% CI 0.50–1.07, respectively), nor were interactions between them.

Parental overweight (default parent model) was predicted by gender but not age: fathers were found to be more often overweight than mothers (OR 1.40; 95% CI 1.19–1.66; Table 3). ADHD above cut-off did not predict overweight in parents.

As shown in Figs. 1 and 2 (separately shown for males and females), compared to the national population prevalence estimates, a higher prevalence of being overweight was measured in all groups compared to the normative data: ADHD-affected youth (OR 1.33, 95% CI 1.13–1.59); unaffected siblings (OR 1.73, 95% CI 1.45–2.08); fathers (OR 1.74, 95% CI 1.40–2.17); mothers (OR 1.78, 95% CI 1.46–2.15). Findings were similar (albeit less significant) when ADHD-affected youth and unaffected siblings were compared to a consecutively measured control cohort of youth (ADHD: OR 1.12, 95% CI 0.91–1.38; unaffected siblings: OR 1.73, 95% CI 1.27–2.34; Tables S4a, S4b, available online).

In a large family-based cohort, we investigated the extent to which associations between ADHD and being overweight are attributable to shared familial factors or specifically linked to ADHD status. We compared the risk of being overweight in individuals with ADHD, their unaffected siblings, and their parents with population normative data and a control family-based cohort. The three assessment waves yielded N = 1828 youth assessments and N = 998 parent assessments from N = 447 unique families. Results indicated that individuals with ADHD showed overweight at an increased prevalence when compared to the general population and the control cohort, but not when compared to their unaffected siblings. Unaffected siblings, mothers, and fathers of individuals with ADHD were just as likely to be overweight as their family member with ADHD. Parental overweight—but not parental ADHD—was predictive of offspring overweight. Age, gender, use of psychostimulants, antipsychotics, and melatonin did not predict the risk for being overweight in ADHD-affected individuals.

Results of the current study suggest that increased prevalence rates of being overweight in ADHD-affected individuals [1, 2, 45‐47] are likely based on factors shared in families. Similar to the results of a large case registry study which showed increased risk for ADHD in families with at least one family member being overweight [5], our study showed an increased risk for overweight in families with at least one family member with ADHD. Thus, there seems to be a common cause in the family environment rather than a causal relationship between ADHD and overweight. This is not in line with a recent review on ADHD and overweight [24], hypothesizing that the association between ADHD and overweight may be primarily linked to deficits in hot executive functions, characterized by impulsivity and difficulties in postponing gratification. The results are in line with another study suggesting the association between ADHD and overweight was completely explained by cumulative psychosocial risks [19]. Prime candidate environmental factors that increase the risk for both ADHD and overweight and that are shared by family members include inadequate health behaviors, foremost poor nutritional habits and lack of physical activity [48‐51] as well as chronic stress [19]. Poor nutritional habits, lack of physical activity, and chronic stress tend to cluster with each other and within families [19], particularly in families with disadvantaged backgrounds [52]. Each of these factors is known to have direct (enhanced eating) and indirect detrimental effects on weight, and more broadly on physical and mental health [21, 29, 53], e.g., by impacting inflammatory and immune systems and subcellular metabolism [54].

In addition to inadequate health behaviors, genetic factors shared by family members may also account for the link at a population level between ADHD and overweight. Candidate gene studies [15‐17] and large-scale genetic correlation based on genome-wide association studies of common genetic variants [18] have shown that genetic factors influencing, e.g., food responsiveness, cognitive and emotional control, dopamine neurotransmission, and circadian rhythm may increase the risk for ADHD and overweight. These variants are likely more prevalent in families where ADHD and/or overweight are present and may explain why some family members develop ADHD, others overweight and others a combination of both. So common genes may be partly responsible for an obesogenic family environment (e.g., lack of parental structuring and guidance [55]) and this same environment increases the risk for ADHD [56, 57]. A recent study suggest that potential genetic mechanisms underlying the association between ADHD and overweight may be sex specific and more pronounced in females than males [13]. However, the current findings were not moderated by sex and suggest that there is a risk of overestimating the association between ADHD and weight since no association between ADHD and overweight was present when correcting for the combined genetic and environmental factors that are shared between affected and unaffected family members. Future work in twin studies may further tease apart the genetic and shared environmental influences accounting for the association between the two phenotypes. It has further been shown recently that gene × environment interactions are of increasing importance for BMI with increasing age [58]. Taking into account both the genetic background and environmental influences in future studies is crucial for a better understanding of the development of overweight and ADHD within families.

Although previous studies reported a negative association between psychostimulant use and BMI [26, 27], our study did not find support for this association. This may suggest that reducing ADHD symptoms with pharmacological treatment is not an effective treatment for overweight status as has been hypothesized previously [59]. Unexpectedly, the use of antipsychotics (known obesogenic medication [60, 61]) was not associated with an increased risk for being overweight either. A potential explanation is that weight gain is a well-known side effect of this medication [28]; individuals at risk for being overweight might, therefore, be less likely to be prescribed antipsychotic or sleep medication, and/or their nutritional patterns might be more strictly monitored. In this study, medication use covered the 4 months prior to assessment but not the time period before, making it possible that the effect of medication on overweight may have been underestimated. It may also be argued that the effect of medication on BMI is small and not likely to make the difference between overweight versus a healthy weight; our dichotomous outcome measure may have reduced the chance of finding an association.

Strengths of the study include the large, family-based cohort allowing for within-family comparisons of the relationship between ADHD and being overweight. Thorough diagnostic data were available for all youth; height and weight were obtained through reliable direct measurements rather than through self-report. Both population prevalence data and a control group were used for comparisons, yielding similar results. As a potential weakness, fewer parental data than offspring data were available since parents were not assessed at all time points. However, results for the subsample with parent data available were fully consistent with the results of the larger sample, indicating that the subsample with parental data was representative of the full sample. Parental ADHD was recorded using self-report, which is less optimal compared to structured diagnostic assessment. Nevertheless, results for parental ADHD data on overweight (i.e., no relationship) were fully in line with the absence of an association between ADHD and overweight in youth using thorough diagnostic procedures for ADHD. Also, several predictors (diagnosis, medication) as well as the outcome measure (overweight) were dichotomized for the purpose of potentially having a clear-cut message based on clinically meaningful variables. Dichotomous predictors and outcome may reduce the chances of finding more subtle effects due to loss of information, yet the large sample size makes it unlikely that this explains the absence of an association between ADHD and being overweight within families. Thereby, comorbid conditions (like depression) associated with overweight were not included in the analyses. However, this does not alter the absence of an association between ADHD and overweight within families.

In conclusion, our results indicate that being overweight runs in ADHD families, yet is not specifically linked to ADHD within these families. Inadequate health behaviors such as poor nutritional habits, lack of physical activity, or chronic stress as well as genetic factors shared by family members likely explain the findings. Gene × environment interaction studies including inadequate health behaviors and chronic stress on mental and physical health should be an important research priority. Given the profound negative health consequences of being overweight, more attention to intervention strategies targeting inadequate health behaviors in families of children with ADHD is a clinically important issue.