From the Guidelines
The pathogenesis of ADHD involves complex interactions between genetic, neurobiological, and environmental factors, primarily stemming from dysregulation in neurotransmitter systems, particularly dopamine and norepinephrine, which are crucial for attention, motivation, and executive functioning. The disorder is characterized by symptoms of inattention, hyperactivity, and impulsivity, which can be categorized into different types, including predominantly inattentive type, predominantly hyperactive-impulsive type, and combined type, as outlined in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition 1. Key factors contributing to ADHD include:
- Genetic factors, with heritability estimates of 70-80%, involving multiple genes that affect neurotransmitter regulation, receptor sensitivity, and neural development
- Neuroimaging studies revealing structural and functional differences in ADHD brains, particularly in the prefrontal cortex, basal ganglia, and cerebellum—regions responsible for impulse control, attention, and motor coordination
- Environmental factors such as prenatal exposure to toxins, premature birth, low birth weight, and psychosocial adversity, which can increase ADHD risk, particularly in genetically susceptible individuals These abnormalities lead to deficits in executive functions like working memory, inhibitory control, and cognitive flexibility, as discussed in various studies 1. The disorder manifests as a developmental delay in self-regulation and executive function rather than a complete absence of these abilities, explaining why symptoms often improve with age as brain development continues, though many individuals continue to experience challenges into adulthood. According to recent guidelines, a comprehensive treatment approach, including pharmacological and non-pharmacological interventions, is recommended for managing ADHD, with the goal of improving symptoms and quality of life 1.
From the Research
Pathogenesis of ADHD
The pathogenesis of Attention-Deficit/Hyperactivity Disorder (ADHD) is a complex process that involves multiple factors, including genetic, environmental, and neurobiological components.
- Genetic studies have shown that ADHD has a heritability of ∼60-75%, suggesting that a plethora of genes, each with a small but significant effect, interact with environmental factors to increase the susceptibility to ADHD 2.
- Neurobiological research has identified alterations in brain structure and function, including developmentally abnormal brain networks related to cognition, attention, emotion, and sensorimotor functions 2, 3.
- At a molecular level, alterations in multiple neurotransmitter systems, including the dopaminergic, adrenergic, serotoninergic, and cholinergic pathways, have been linked to ADHD 2, 4.
Neurobiological Factors
Neurobiological factors, such as brain functioning alterations, have been confirmed by neurophysiological findings, showing that individuals with ADHD have elevated theta/beta power ratios, and less pronounced responses and longer latencies of event-related potentials, compared with controls 2.
- Functional MRI has documented a specific deficit of frontostriatal networks in ADHD 3.
- The volume of both the total brain and various regions, including the prefrontal cortex, the caudate nucleus, and the vermis of the cerebellum, is smaller in ADHD 3.
Clinical Heterogeneity
ADHD is a heterogeneous disorder, with considerable clinical heterogeneity resulting from frequent associations with various co-morbidities, the impact of the disorder on psychosocial functioning, and gender effects 5, 3.