From the Guidelines
The pathophysiology of ADHD is characterized by dysregulation in brain neurotransmitter systems, particularly dopamine and norepinephrine, leading to executive function deficits and structural and functional abnormalities in brain regions such as the prefrontal cortex, basal ganglia, and cerebellum. According to the most recent study 1, ADHD is a complex neurological condition that affects brain development and function, with a strong genetic component and heritability estimated at 70-80%. The disorder is associated with reduced volume and activity in brain regions responsible for executive functions, including attention, impulse control, and working memory.
Key Findings
- The study 1 highlights the importance of considering the heterogeneity of ADHD symptoms and the need for individualized treatment approaches.
- The evidence suggests that ADHD is not limited to childhood or adolescence, but rather shows a high persistence into adulthood, with an estimated prevalence of 2.5% in adults 1.
- The diagnostic process for ADHD is challenging and relies on a comprehensive clinical interview, behavioral observation, and assessment tools such as rating scales and semi-/structured interviews 1.
Pathophysiology
The pathophysiology of ADHD involves dysregulation in brain neurotransmitter systems, particularly dopamine and norepinephrine, which are crucial for executive functions like attention, impulse control, and working memory. Neuroimaging studies show reduced volume and activity in brain regions responsible for these functions, including the prefrontal cortex, basal ganglia, and cerebellum. The disorder has a strong genetic component, with specific genes affecting dopamine receptors and transporters (like DAT1 and DRD4) implicated. Environmental factors such as prenatal exposure to toxins, premature birth, and low birth weight may also contribute.
Treatment
The most effective treatments for ADHD, such as stimulant medications like methylphenidate (Ritalin) and amphetamine compounds (Adderall), work by increasing dopamine and norepinephrine availability in the synaptic cleft, improving signal transmission between neurons and enhancing executive function 1. Non-stimulants like atomoxetine (Strattera) work primarily on norepinephrine pathways. The optimal management approach for ADHD is individualized and may include behavior therapies, academic accommodations, pharmacotherapy, and psychological interventions to manage associated features and comorbid diagnoses.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Pathophysiology of ADHD
The pathophysiology of Attention-Deficit Hyperactivity Disorder (ADHD) is complex and involves multiple neural networks and systems. Key aspects include:
- Impairment of executive functions, such as behavioral inhibition, attention, self-regulation, working memory, planning, and cognitive flexibility 2
- Involvement of the frontostriatal network, including the lateral prefrontal cortex, dorsal anterior cingulate cortex, caudate nucleus, and putamen 2
- Abnormalities in other cortical regions, such as the temporal lobe, parietal lobe, occipital lobe, and lateral ventricles 2
- Widespread reductions in volume throughout the cerebrum and cerebellum, as well as hypoactivation of certain brain areas, including the dorsal anterior cingulate cortex, frontal cortex, and basal ganglia (striatum) 2
Neurochemical Basis
The neurochemical basis of ADHD is thought to involve a dopamine/norepinephrine deficit, as medications such as methylphenidate, amphetamine, and atomoxetine, which target these neurotransmitters, are effective in treating the disorder 3
Heterogeneity of ADHD
ADHD is a heterogeneous disorder, with different subtypes (inattentive, hyperactive-impulsive, and combined) and associated problems, such as oppositional defiant/conduct or tic disorder 4
- The disorder can also be characterized by cognitive and motivational problems, as well as resting-state abnormalities associated with impaired brain activity in distinct neuronal networks 4
Current Understanding
Current understanding of the pathophysiology of ADHD is based on scientific and clinical studies that have challenged traditional conceptions of the disorder 5
- Research has highlighted the importance of considering the broader clinical needs of individuals with ADHD, particularly over the longer term, and the potential benefits of non-pharmacological approaches to treatment 5