Table 2.

Neurobiologic Mechanisms of ADHD.

Anatomical correlates

Smaller total brain volume (including frontal lobe, caudate nucleus, and cerebellum)

Reduced thickness of prefrontal and other cortical regions

Functional correlates

Alterations in connectivity in frontostriatal, frontoparietal, frontocerebellar, and parieto-occipital pathways and in the cingulate cortex

Decreased activity in the networks involved with executive function and with attention, and increased activity in the default mode network, which is deactivated during cognitive tasks and is implicated in mind wandering and interoception

Delayed brain maturation

Neurochemical factors

Dysregulation of dorsal striatal and ventral striatal dopamine systems

Dysregulation of noradrenaline systems

Genetic risk factors

Heritability of approximately 0.8

At least 18 ADHD-susceptibility genes (including the dopamine receptors D4 (DRD4) and D5, dopamine transporter (DAT1), serotonin receptor 1B, and synaptosomal-associated protein 25), but without specificity; 7-repeat allele of DRD4 most strongly implicated

Small effect sizes in molecular genetic analyses and genomewide association studies

Environmental and clinical risk factors

Prenatal exposure to alcohol, tobacco, and lead

Complications of pregnancy and birth

Neonatal anoxia, seizures, and brain injury

Obesity and diabetes

Gene–environment interactions

Interaction between genetic variants (DRD4 and DAT1) and environmental factors such as maternal smoking during pregnancy