Genetics in the ADHD Clinic: How Can Genetic Testing Support the Current Clinical Practice?

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with a childhood prevalence of 5%. In about two-thirds of the cases, ADHD symptoms persist into adulthood and often cause significant functional impairment. Based on the results of family and twin studies, the estimated heritability of ADHD approximates 80%, suggests a significant genetic component in the etiological background of the disorder; however, the potential genetic effects on disease risk, symptom severity, and persistence are unclear. This article provides a brief review of the genome-wide and candidate gene association studies with a focus on the clinical aspects, summarizing findings of ADHD disease risk, ADHD core symptoms as dimensional traits, and other traits frequently associated with ADHD, which may contribute to the susceptibility to other comorbid psychiatric disorders. Furthermore, neuropsychological impairment and measures from neuroimaging and electrophysiological paradigms, emerging as potential biomarkers, also provide a prominent target for molecular genetic studies, since they lie in the pathway from genes to behavior; therefore, they can contribute to the understanding of the underlying neurobiological mechanisms and the interindividual heterogeneity of clinical symptoms. Beyond the aforementioned aspects, throughout the review, we also give a brief summary of the genetic results, including polygenic risk scores that can potentially predict individual response to different treatment options and may offer a possibility for personalized treatment for the therapy of ADHD in the future.

Disrupted structural connectivity and less efficient network system in patients with the treatment-naive adult attention-deficit/hyperactivity disorder

“…Although there were no obvious psychiatric comorbidities in our sample, adult ADHD is often associated with psychiatric comorbidities and a high prevalence of depression has also been reported ( 39 ). Common genetic factors for ADHD and depression have been reported as contributing to this phenomenon ( 40 ). Therefore, we speculate that abnormalities of these regions seem to be associated with not only cognitive disability but also susceptibility to depressive disorder in adult ADHD.…”

“…The corticostriatal projections are critical components of forebrain circuits that are extensively involved in motivated behavior ( 28 ). Not only decreased connectivity but also overconnectivity may also disrupt structural connectivity and information transfer, and some studies demonstrated overconnectivity in patients with ASD ( 40 ). The corticostriatal circuits have been linked to dopaminergic pathways that connect the striatum to the prefrontal cortex and other areas, and dysfunction of these circuits has been linked to impairments in cognitive functions and the ability to adapt behavior to changing circumstances ( 44 ).…”

Aggressiveness in Italian Children with ADHD: MAOA Gene Polymorphism Involvement

“…Genes encoding the dopamine receptors (e.g., DRD2 and DRD4), dopamine transporter (DAT1), and monoamine oxidase (MAOA) enzymes, such as catechol-Omethyltransferase (COMT) and dopamine beta-hydroxylase (DBH), are the most studied [12][13][14]. However, the influence of genetics on disease risk needs to be better understood [15]. Children with ADHD can also exhibit hostility or anger and aggressive behavior.…”

Characteristics of Attention-Deficit/Hyperactivity Disorder Subtypes in Children Classified Using Quantitative Electroencephalography

“…14 Neuroimaging, genetic, and electrophysiological studies have been conducted aiming to discover pathophysiological and biological markers for ADHD. 15,16 Quantitative electroencephalography (QEEG) can detect subtle changes in EEG that are difficult to discriminate visually, and it is known to have greater accessibility and safety compared with other examination methods. 17,18 Accordingly, there have been attempts to use QEEG to distinguish between normal children and children with ADHD.…”