1. Overview

Attention-Deficit/Hyperactivity Disorder (ADHD) is a complex neurodevelopmental disorder characterized by patterns of inattention, hyperactivity, and impulsivity. Prevalence estimates suggest that ADHD affects approximately 5–7% of children and 2.5% of adults worldwide. The disorder persists across the lifespan and is associated with significant functional impairment.

2. Neurobiological Basis

2.1 Brain Structure and Function

  • Prefrontal Cortex: Reduced volume and activity, especially in the dorsolateral prefrontal cortex (DLPFC), which is critical for executive function.
  • Basal Ganglia: Abnormalities in the caudate nucleus and putamen, affecting motor control and behavioral inhibition.
  • Cerebellum: Smaller posterior inferior vermis, impacting timing and coordination.

ADHD Brain Differences

Figure: Brain regions implicated in ADHD (highlighted)

2.2 Neurotransmitter Systems

  • Dopamine: Dysregulation in mesocortical and mesolimbic pathways; reduced dopamine transporter density.
  • Norepinephrine: Altered signaling in prefrontal cortex circuits.
  • Glutamate/GABA: Imbalance may contribute to cortical excitability and inhibition deficits.

3. Genetic and Environmental Factors

3.1 Genetics

  • Heritability: Twin studies estimate heritability at 70–80%.
  • Candidate Genes: DRD4, DAT1, SNAP-25, and others linked to dopamine regulation.

3.2 Environmental Influences

  • Prenatal: Maternal smoking, alcohol use, and stress.
  • Postnatal: Lead exposure, low birth weight, early psychosocial adversity.

4. Cognitive and Behavioral Features

  • Inattention: Difficulty sustaining focus, disorganization, forgetfulness.
  • Hyperactivity: Fidgeting, inability to stay seated, excessive talking.
  • Impulsivity: Interrupting, risk-taking, poor self-control.

5. Diagnostic Criteria (DSM-5)

  • Symptoms: ≥6 symptoms of inattention and/or hyperactivity-impulsivity for at least 6 months.
  • Onset: Several symptoms present before age 12.
  • Impairment: Symptoms interfere with social, academic, or occupational functioning.
  • Exclusion: Not better explained by another disorder.

6. Case Studies

Case 1: Adult ADHD

A 22-year-old university student reports chronic disorganization, missed deadlines, and difficulty focusing during lectures. Neuropsychological assessment reveals deficits in working memory and response inhibition. Stimulant medication and cognitive behavioral therapy (CBT) improve academic performance.

Case 2: Pediatric ADHD with Comorbidity

An 8-year-old presents with hyperactivity and impulsivity, alongside oppositional defiant disorder (ODD). Multimodal treatment—behavioral interventions, parent training, and low-dose methylphenidate—reduces both ADHD and ODD symptoms.

Case 3: ADHD and Substance Use

A 17-year-old with untreated ADHD develops cannabis use disorder. After initiation of non-stimulant therapy (atomoxetine) and motivational interviewing, substance use decreases and executive function improves.

7. Mnemonic for ADHD Symptoms

“FIDGETS”

  • Fails to give close attention
  • Impulsivity
  • Difficulty sustaining attention
  • Goes off task
  • Easily distracted
  • Talks excessively
  • Squirms/fidgets

8. Treatment Approaches

8.1 Pharmacological

  • Stimulants: Methylphenidate, amphetamines (increase synaptic dopamine/norepinephrine).
  • Non-stimulants: Atomoxetine, guanfacine, clonidine.

8.2 Non-Pharmacological

  • CBT: Focuses on executive dysfunction and coping strategies.
  • Psychoeducation: For patients, families, and educators.
  • Neurofeedback: Modest evidence for effectiveness.

9. Surprising Facts

  1. ADHD and Creativity: Recent studies suggest higher divergent thinking and creative potential in some individuals with ADHD traits.
  2. Delayed Brain Maturation: Cortical thinning and delayed peak thickness in the prefrontal cortex can lag by up to 3 years in children with ADHD.
  3. Sleep Disorders: Up to 70% of individuals with ADHD experience sleep disturbances, such as delayed sleep phase syndrome, independent of medication effects.

10. Ethical Issues

  • Overdiagnosis and Medicalization: Concerns about labeling normal childhood behavior as pathological.
  • Stimulant Misuse: Non-prescribed use of ADHD medication among students for cognitive enhancement.
  • Access and Equity: Disparities in diagnosis and treatment based on socioeconomic status, race, and gender.
  • Informed Consent: Ensuring patients and families understand benefits and risks of medication.

11. Recent Research

A 2023 study in Nature Genetics identified over 27 risk loci for ADHD, supporting a polygenic model and implicating synaptic and neurodevelopmental pathways (Demontis et al., 2023). This advances understanding of the genetic architecture and potential for personalized interventions.

Reference:
Demontis, D., Walters, R.K., Martin, J. et al. (2023). Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several causal genes. Nature Genetics, 55, 198–207. https://www.nature.com/articles/s41588-022-01221-4

12. Unique Insights

  • Neurodevelopmental Trajectory: ADHD is increasingly viewed as a spectrum disorder with variable persistence and outcomes, influenced by gene-environment interplay.
  • Digital Phenotyping: Use of smartphones and wearables to monitor attention and behavior in real time is an emerging research area.
  • Transdiagnostic Overlap: Shared genetic risk with autism, mood disorders, and learning disabilities suggests overlapping neurobiological pathways.

13. Diagram: ADHD Pathophysiology

ADHD Pathophysiology

Figure: Schematic of neurobiological pathways in ADHD

14. Conclusion

ADHD is a multifactorial disorder with complex neurobiological, genetic, and environmental underpinnings. Advances in genomics, neuroimaging, and digital health are reshaping diagnosis and intervention. Ethical considerations remain central to responsible care and research.