ADHD and metabolic-cardiovascular outcomes: Investigating links, underlying mechanisms and risk factors

Attention-deficit/hyperactivity disorder (ADHD) is a common and persistent neurodevelopmental disorder that causes substantial impairment in approximately 5% of children and 3% of adults(1,2). Individuals with ADHD are also likely to display elevated levels of other psychiatric disorders in young and middle adulthood(2,3). Emerging evidence from recent studies also suggests a link between ADHD and serious physical health conditions in older age, such as metabolic and cardiovascular disease (3-5). However, an understanding of why there is an increased risk of these conditions in ADHD is currently while quantitative and molecular genetic research have consistently shown that the co-occurrence of ADHD with psychiatric conditions is largely due to shared genetic factors(6,7), there are only a few studies investigating the aetiological factors underlying the co-occurrence with physical health conditions. Recent genetic studies reveal novel, weak-to-moderate genetic correlations between ADHD and obesity, diabetes, and low HDL cholesterol levels(7,8), but conclusive and well-powered studies are lacking. 
Some lifestyle factors and health conditions are putative consequences of ADHD as well as established risk factors for metabolic and cardiovascular disease, such as smoking, depression, poor diet, sleep problems and physical inactivity(2,3,9). However, there is a lack of studies outlining the extent to which lifestyle factors and comorbid health conditions mediate the link of ADHD with metabolic and cardiovascular disease. 
The main goal in this proposal is to investigate the underlying mechanisms and mediating risk factors that contribute to metabolic and cardiovascular disease in individuals with ADHD. Firstly, we propose to estimate the genetic associations between ADHD and metabolic-cardiovascular disease and related objective risk indicators (e.g. cholesterol and glucose levels, blood pressure, body mass index, heart rate, heart rate variability), and explore the specific gene sets and pathways that are driving any identified genetic overlap. Secondly, we will investigate which specific lifestyle factors and comorbid conditions increase risk for metabolic-cardiovascular disease in ADHD. We aim to exploit the large-scale and detailed phenotypic and genetic data in Lifelines and make use of its family design to tackle these research questions. 
It is of great importance to increase our knowledge of ADHD across adulthood and to better understand the mechanisms that contribute to physical health problems in these individuals. If we know how to predict individuals with ADHD at risk of later-onset health issues, and can identify the risk factors that are at play, we will be in a much better position to prevent and treat such health issues in ADHD.