ADHD co-morbidities: A review of implication of gene × environment effects with dopamine-related genes
Graphical Abstract
Section snippets
ADHD and comorbidity; genes and environments
Attention deficit hyperactivity disorder (ADHD) is a growing public health concern, addressed in multiple genetic studies. This review has the objective to summarize the findings with focus on two aspects: on the dopaminergic system where the culprit of ADHD, according to correlative and experimental studies in animals and humans, is likely to lie, and on the role of environment(s) that may mold the genetic predispositions into pathogenetic process. To that end the major dopamine system shaping
ADHD and dopamine
As the genetic studies reveal a contribution of multiple genes to ADHD, the underlying pathogenesis of the disorder remains unknown. One of the most plausible hypotheses implies that genes with impact on the central dopamine system are implicated in the etiopathology of ADHD, and that might interact with environmental conditions. This gains support from multiple, converging lines of evidence. Drugs used to treat ADHD act on catecholaminergic neurotransmission, and both cortical and subcortical
Dopamine gene variants and G × E with particular reference to ADHD
The general theme of G × E in ADHD will receive limited treatment here as it is extensive on its own and has been recently reviewed elsewhere (Franke and Buitelaar, 2018, Nigg et al., 2010). The reports on candidate gene variants and environmental factors moderating each other in the development of ADHD represent a large variety of genotypes and environmental factors, and herewith the focus will be on the dopamine system. Indeed, dopamine-related genes have been examined most often, and DRD4,
Co-morbidity of ADHD with depression and negative emotionality, addiction and substance use disorders (SUD), and obesity and eating disorders
In community samples the rate of major depressive disorder in youths with ADHD is 5.5 times higher than in youths without ADHD; rates in different studies have been in the range of 12.5–50% (Angold et al., 1999). In clinical samples the comorbidity rate is even higher (Daviss, 2008). The prevalence of clinical depression is more than nine times higher in adults with ADHD (Chen et al., 2018). Depression, similarly to ADHD, is a dimensional state, and persistent negative emotionality, including
Caveats and perspectives
In summary, the role of dopamine neurons and genes encoding the pivotal proteins for dopaminergic neurotransmission in ADHD, depression, substance use disorders and obesity is beyond doubt, and that they are involved in the frequently occurring co-morbidity of ADHD with these other conditions is highly likely. Nonetheless, direct evidence for this mostly remains to be produced. A large number of factors that has placed limitations to relevant studies exist and these have to be addressed in
Acknowledgments
This research was supported by the Estonian Research Council (PRG1213) and the European Commission Horizon 2020 Programme Projects CoCA (No 667302) and Eat2beNICE (No 728018).
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