ADHD Etiology—From Gene to Large Brain Network

1. Inside a Neuron Cell—Genetic Level

  • Heritability: Inherited genetic predisposition

  • Candidate Genes:

    • DAT1 (Dopamine Transporter Gene)

    • DRD4 (Dopamine Receptor D4 Gene)

    • 5-HTTLPR (Serotonin Transporter Gene)

  • GWAS Loci: Genetic risk loci identified through genome-wide association studies

2. Between Neuron Cells—Molecular and Cellular Level

  • Neurotransmitter Dysregulation:

    • Dopamine: Affects reward processing, motivation, and executive functions

    • Norepinephrine: Crucial for attention and arousal

    • Serotonin: Influences mood regulation and impulsivity

  • Neural Development:

    • Delayed maturation of the prefrontal cortex

    • Abnormal synaptic pruning

  • Neuroinflammation: Inflammatory cytokines affecting brain development and neurotransmitter function

3. Large Cluster of Cells—Brain Areas

  • Prefrontal Cortex: Underactivity affects executive functions, attention regulation, and impulse control

  • Basal Ganglia: Structural and functional abnormalities affect motor control and behavioral regulation

  • Anterior Cingulate Cortex (ACC): Dysfunction leads to attentional and emotional dysregulation

  • Cerebellum: Reduced volume affects motor control and cognitive processes

4. Between Brain Areas—Cross Region Neurological Networks

  • Default Mode Network (DMN): Mainly includes medial prefrontal cortex and posterior cingulate cortex. Abnormal activity patterns lead to distractibility

  • Frontostriatal Circuitry: Disruptions lead to difficulties with self-regulation and executive functions

  • Connectivity and Network Models:

    • Hypo-connectivity: Reduced connectivity between the prefrontal cortex and other brain regions

    • Hyper-connectivity: Excessive connectivity within certain networks