The Biology of ADHD: What Science Tells Us

stephaniekustner
Oct 6
3 min read

Attention-Deficit/Hyperactivity Disorder (ADHD) is one of the most researched neurodevelopmental conditions. While its symptoms—such as distractibility, impulsivity, and restlessness—are easily observed, the underlying biology is more complex. Advances in genetics, neuroimaging, and neuroscience have provided clearer insights into how ADHD develops and why it presents differently across individuals.

Genetic Foundations

ADHD is strongly heritable. Twin studies estimate heritability at 70–80%, making genetics a major contributor to risk.

Polygenic nature: No single “ADHD gene” exists. Instead, hundreds of common genetic variants each contribute a small effect.
Neurotransmitter genes: Variants linked to dopamine regulation (e.g., DRD4, DAT1/SLC6A3) and norepinephrine function are consistently associated with ADHD.
Genetic overlap: Large genome-wide association studies (GWAS) reveal overlap between ADHD and conditions such as autism, depression, and learning disorders, helping to explain common comorbidities.

Brain Structure

Mega-analyses combining MRI scans from thousands of participants have highlighted subtle but consistent differences in brain structure in people with ADHD.

Subcortical regions: Reduced volumes in the caudate nucleus, putamen, nucleus accumbens, and hippocampus have been reported in children with ADHD. These regions play roles in attention, reward processing, and memory.
Cortical development: Studies suggest delayed cortical maturation, particularly in the prefrontal cortex, which supports executive functions like planning and inhibition.
Asymmetry: Some findings indicate atypical hemispheric asymmetry, especially in fronto-striatal circuits, which may contribute to attentional control difficulties.

Importantly, these differences are small at the group level—brain scans cannot “diagnose” ADHD in individuals.

Brain Function and Connectivity

Beyond structure, functional brain activity and connectivity patterns are altered in ADHD.

Frontostriatal circuitry: Underactivation of the prefrontal cortex and basal ganglia is consistently observed in tasks requiring sustained attention and inhibition.
Default mode network (DMN): People with ADHD often show difficulty suppressing DMN activity during tasks, leading to mind-wandering and distractibility.
Network variability: Resting-state fMRI reveals increased variability in connectivity, particularly in attention-related networks. This “instability” may underpin fluctuations in focus.

Neurochemistry

ADHD has long been linked to alterations in neurotransmitter systems:

Dopamine: Plays a central role in motivation, reward processing, and reinforcement learning. Evidence suggests reduced dopamine transporter availability and dysregulated dopamine signaling in ADHD.
Norepinephrine: Involved in alertness and arousal. Imbalances may contribute to impaired sustained attention.
Glutamate and GABA: Emerging studies suggest that excitatory–inhibitory imbalance in cortical circuits may also play a role, though findings are less consistent than with dopamine/norepinephrine.

The effectiveness of stimulant medications (e.g., methylphenidate, amphetamines) supports these findings—they increase dopamine and norepinephrine availability in key brain regions, improving regulation of attention and behavior.

Environmental Interactions

While biology plays a major role, environment interacts with genetic vulnerability:

Prenatal risks: Low birth weight, prematurity, and maternal smoking or alcohol use during pregnancy are associated with increased ADHD risk.
Toxins: Lead exposure and certain early-life stressors may exacerbate risk.
Protective factors: Stable environments, supportive parenting, and access to early interventions can reduce impairment even in children with biological vulnerabilities.

Putting It Together

ADHD is best understood as a neurodevelopmental condition with strong genetic underpinnings and identifiable brain differences. These biological factors interact with life experiences to shape how symptoms appear in each person. Recognizing ADHD as rooted in biology helps reduce stigma—it is not a matter of laziness or poor discipline, but of brain development and function.

References

Faraone, S. V., & Larsson, H. (2019). Genetics of attention deficit hyperactivity disorder. Molecular Psychiatry, 24(4), 562–575.

Demontis, D., et al. (2019). Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder. Nature Genetics, 51, 63–75.

Hoogman, M., et al. (2017). Subcortical brain volume differences in participants with attention deficit hyperactivity disorder in children and adults: a cross-sectional mega-analysis. The Lancet Psychiatry, 4(4), 310–319.

Shaw, P., et al. (2007). Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation. Proceedings of the National Academy of Sciences, 104(49), 19649–19654.

Castellanos, F. X., & Proal, E. (2012). Large-scale brain systems in ADHD: beyond the prefrontal–striatal model. Trends in Cognitive Sciences, 16(1), 17–26.