2 Neuroscience2.11 Integrated neurobiology of syndromes and states
2.11.2 ADHD
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Written by Resident Doctor Committee · Published
Genetics
Heritability from twin studies is about 0.7 to 0.9, and it is similar in males and females.
ADHD is polygenic. Genome-wide significant loci explain only part of the heritability, and the rest lies mainly in very many common variants of tiny individual effect, not rare large-effect variants or single genes.
ADHD polygenic risk is negatively associated with several cognitive domains, most strongly attention (Demontis genome-wide study, 2023).
Polygenic scores are research tools, not diagnostic tests.
Rare variants and copy number changes overlap with autism, intellectual disability, epilepsy and schizophrenia.
Candidate genes
Gene | What it encodes | Point to remember |
|---|---|---|
DRD4 | A D2-like dopamine receptor | The seven-repeat allele of its exon 3 48-base-pair variable number tandem repeat makes it the best-replicated candidate gene |
SLC6A3 (DAT1) | The dopamine transporter | Methylphenidate binds and blocks it, which stops dopamine reuptake |
Candidate gene effects are small and do not support diagnostic testing.
Environmental risk
The established environmental risk factors are prenatal and perinatal insults, such as prematurity and very low birth weight, and early adversity.
Dietary and biochemical factors are not established risk factors.
Brain development
Prefrontal cortical thickness peaks two to three years late, the greatest delay, while primary motor cortex peaks on time.
Hyperactivity often lessens with age, but inattention and executive difficulties may persist into adulthood.
Comorbidity and diagnosis
Oppositional defiant disorder (about 30 to 50%) is the commonest co-occurring psychiatric disorder in childhood, ahead of conduct disorder, bipolar disorder and substance misuse.
Anxiety, autism, tics and learning disorders also commonly co-occur.
Clinicians diagnose ADHD from developmental history, symptoms across settings and impairment, because scans, genes and cognitive tasks cannot establish it.