## Neurotransmitter Basis of ADHD **Key Point:** ADHD is fundamentally a disorder of catecholamine (dopamine and noradrenaline) dysregulation, particularly affecting the prefrontal cortex and striatum — brain regions critical for executive function, impulse control, and attention. ### Neurobiological Mechanism 1. **Prefrontal cortex involvement**: Dopamine and noradrenaline deficiency impairs working memory, planning, and inhibitory control. 2. **Striatum involvement**: Reduced dopaminergic signalling disrupts reward processing and motivation. 3. **Default mode network**: Abnormal connectivity due to catecholamine imbalance leads to inattention and distractibility. ### Why This Matters for Treatment **High-Yield:** Stimulant medications (methylphenidate, amphetamines) and non-stimulant noradrenaline reuptake inhibitors (atomoxetine) all work by **increasing dopamine and/or noradrenaline availability** in these circuits — validating the catecholamine hypothesis. **Clinical Pearl:** The monoamine hypothesis of ADHD explains why SSRIs (which target serotonin) are NOT first-line agents, despite their use in comorbid depression or anxiety. ### Supporting Evidence - Neuroimaging studies show reduced grey matter volume in prefrontal and striatal regions in ADHD. - Genetic studies implicate genes encoding dopamine receptors (DRD4, DRD5) and the dopamine transporter (DAT). - Catecholamine-enhancing drugs are the most effective pharmacological interventions. [cite:Harrison 21e Ch 387]
Sign up free to access AI-powered MCQ practice with detailed explanations and adaptive learning.