What are the causes of hyperactivity‑restlessness‑attention‑deficit (HRAD) in children?

Causes of Hyperactivity-Restlessness-Attention-Deficit (HRAD) in Children

ADHD in children is a highly heritable neurobiological disorder with genetic factors accounting for the majority of cases, but environmental factors—including prenatal exposures (maternal smoking, alcohol, prematurity), perinatal complications (hypoxic-ischemic injury), and postnatal insults (head trauma, infections, toxins)—contribute significantly and may be preventable. 1, 2, 3

Primary Etiologic Categories

Genetic Factors (Predominant Cause)

• ADHD demonstrates strong heritability, with genetic factors playing the fundamental role in pathogenesis and accounting for the majority of cases in children. 3, 4
• Family studies consistently support the strong familial nature of ADHD, with family history being a significant predictor of the disorder. 5
• Genetic variations influence structural and functional brain changes in ADHD patients, particularly affecting frontostriatal circuitry and dopaminergic pathways. 4, 5
• Multiple genetic studies have observed strong associations with neural abnormalities and delayed neurodevelopment in ADHD. 4

Prenatal Risk Factors

• Maternal smoking during pregnancy is a well-established environmental risk factor that increases ADHD risk in offspring. 2, 5
• Maternal alcohol ingestion during pregnancy contributes to ADHD development. 2
• Prematurity is associated with increased ADHD risk. 2, 4
• Thyroid deficiency during pregnancy may contribute to ADHD pathogenesis. 2
• Genetic factors can determine an individual's responses to environmental exposures, particularly during the prenatal stage. 3

Perinatal Complications

• Hypoxic-ischemic encephalopathy (birth-related oxygen deprivation) is a significant perinatal risk factor. 2
• Pregnancy and delivery complications are considered important risk factors for ADHD development. 5

Postnatal Acquired Factors

• Viral infections, meningitis, and encephalitis can produce ADHD symptoms and have been associated with the disorder since early reports. 2
• Head injury and severe brain trauma can result in ADHD symptomatology. 2, 4
• Exposure to neurodevelopmental toxins, including heavy metals and organohalide pollutants, contributes to ADHD. 6
• Epilepsy and certain medications/drugs are associated with ADHD development. 2
• Neuroinflammation and severe brain injuries are contributing factors. 4

Environmental and Dietary Factors (More Controversial)

• Adverse responses to food additives and food intolerances may contribute to ADHD symptoms in some children. 6
• Sensitivities to environmental chemicals, molds, and fungi have been implicated. 6
• Iron deficiency is a controversial but potentially relevant factor. 2
• Nutrient deficiencies are common in ADHD and may contribute to symptomatology. 6

Neurobiological Mechanisms

• Dysfunction in frontostriatal brain circuitry is apparent in ADHD and underlies core symptoms. 6, 5
• Hypofunctioning of dopaminergic and noradrenergic pathways contributes to ADHD pathophysiology. 6, 5
• MRI studies have demonstrated brain volumetric changes involved in the syndrome's pathophysiology. 2
• Imbalances in dopaminergic and noradrenergic systems are central to ADHD neurobiology. 5

Psychosocial Risk Factors

• Adverse family environment variables are considered important risk factors for ADHD. 5
• Psychosocial adversity is a predictor of ADHD persistence. 5
• Consanguineous marriages may increase risk in certain populations. 4

Critical Clinical Considerations

It is essential to distinguish ADHD from other conditions that can mimic hyperactivity-restlessness-attention-deficit symptoms:

• Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) presents with behavioral disorders but is a distinctly different syndrome from ADHD, typically appearing between ages 1.5-7 years with rapid obesity followed by hypothalamic dysfunction. 1
• Anxiety, depression, oppositional defiant disorder, conduct disorders, learning disabilities, language disorders, sleep disorders (particularly sleep apnea), and tics must be systematically assessed as coexisting or alternative diagnoses. 1
• Environmental influences on behavior must be considered in the diagnostic evaluation. 1

Preventive Implications

Early prenatal recognition, prevention, and treatment of environmental etiologies may reduce reliance on symptomatic medication management, addressing parental concerns about pharmacotherapy. 2