Which neurotransmitter system dysfunction is considered the primary neurobiological basis of Attention-Deficit/Hyperactivity Disorder (ADHD)?

Explanation

## Neurobiological Basis of ADHD **Key Point:** The catecholamine hypothesis of ADHD implicates dysregulation of dopamine (DA) and norepinephrine (NE) in the prefrontal cortex (PFC) and striatum as the primary neurobiological mechanism. ### Dopamine and Norepinephrine Dysfunction 1. **Prefrontal cortex involvement** - DA and NE regulate executive functions (working memory, inhibition, attention) - Hypoactivity in PFC → poor impulse control and inattention 2. **Striatum involvement** - DA dysregulation → impaired reward processing and motivation - Affects motor control and habit formation 3. **Neurochemical basis of medication response** - Stimulants (methylphenidate, amphetamines) increase DA and NE availability - Atomoxetine (non-stimulant) selectively increases NE - Both classes improve core ADHD symptoms, confirming catecholamine hypothesis **High-Yield:** The catecholamine hypothesis explains why stimulants and atomoxetine are effective treatments — they restore DA/NE balance in PFC and striatum. **Clinical Pearl:** Neuroimaging studies show reduced activation in dorsolateral PFC and anterior cingulate cortex in individuals with ADHD, supporting the catecholamine model. ### Why Other Systems Are Secondary | System | Role in ADHD | Evidence | |--------|-------------|----------| | Serotonin | Mood, impulse control | Not primary; SSRIs ineffective for core ADHD symptoms | | Acetylcholine | Attention, memory | Not primary mechanism; anticholinergics worsen ADHD | | GABA | Inhibition | Secondary; involved in comorbid anxiety, not core ADHD |