Attention-deficit hyperactivity disorder (ADHD), or hyperkinetic disorder (HKD), is acknowledged to have an underlying genetic component.1,2
- Pooled data from 20 twin studies estimated the mean heritability of ADHD to be 76% (study data from the United States, the European Union, Scandinavia and Australia), indicating that ADHD has a high rate of heritability.3
- Using data from the Swedish Twin Registry (n=37,714 adult twins), researchers estimated that the genetic contribution to ADHD was 72% in adult twins.1
Furthermore, in a second Swedish study, 52% of the correlation between inattentive and hyperactive-impulsive symptoms is accounted for by genetic influences, and 48% by non-shared environmental influences (n=15,198 adult twin pairs).2
A study of 25 children and adolescents with ADHD (aged 5–18 years) who were adopted within the first year of life reported that rates of ADHD are significantly higher between biological relatives (parent–child or sibling) compared with adoptive relatives.4
- In the adopted ADHD group, 6% of adoptive parents and 8% of adoptive siblings had symptoms of ADHD.
- In a control group of 101 children and adolescents with ADHD who had not been adopted and lived with their biological families, 18% of parents and 31% of siblings had symptoms of ADHD.
Molecular genetics of ADHD
The molecular genetics of ADHD is an evolving field; nevertheless, studies have reported many candidate genes to be associated with the disorder.
Potential biomarkers of ADHD
From the available literature, a hypothetical pyramid representation of possible signature sets of biomarkers for ADHD diagnosis has been developed.5
Genomic, neurophysiological/neuropsychological, neuroimaging, pharmacogenomic and proteomic data were reviewed and used to build the pyramid, where the best candidate biomarkers are at the top, and the least promising biomarkers are at the bottom (Figure).5 The putative set of biomarkers included:
- Useful biomarkers5
- Variants in DAT1 and DRD4 genes are the best candidates for useful biomarkers due to their associations with neuropsychological tasks, activation in specific brain areas, methylphenidate response and gene expression levels.
- Noradrenergic system (norepinephrine transporter, norepinephrine, 3-methoxy-4-hydroxyphenylglycol, monoamine oxidase, neuropeptide Y) due to their altered peripheral levels, their association with neuropsychological tasks, symptomatology drug effect and brain function.
- Dopamine beta hydroxylase and catechol-O-methyltransferase.
- Probably not useful biomarkers5
- Endophenotype biomarkers: in particular, working memory, selective attention vigilance/sustained attention, theta/beta ratio, reaction-time variability and neuropsychological endophenotypes.
Figure: A hypothetical pyramid representation of possible signature sets of biomarkers for ADHD diagnosis. Reproduced with kind permission from Faraone SV et al. Curr Psychiatry Res 2014; 6: 497.5
- Larsson H, Chang Z, D’Onofrio BM, et al. The heritability of clinically diagnosed attention deficit hyperactivity disorder across the lifespan. Psychol Med 2014; 44: 2223-2229.
- Larsson H, Asherson P, Chang Z, et al. Genetic and environmental influences on adult attention deficit hyperactivity disorder symptoms: a large Swedish population-based study of twins. Psychol Med 2013; 43: 197-207.
- Faraone SV, Perlis RH, Doyle AE, et al. Molecular genetics of attention-deficit/hyperactivity disorder. Biol Psychiatry 2005; 57: 1313-1323.
- Sprich S, Biederman J, Crawford MH, et al. Adoptive and biological families of children and adolescents with ADHD. J Am Acad Child Adolesc Psychiatry 2000; 39: 1432-1437.
- Faraone SV, Bonvicini C, Scassellati C. Biomarkers in the diagnosis of ADHD–promising directions. Curr Psychiatry Rep 2014; 16: 497.