ATTENTION DEFICIT/HYPERACTIVITY DISORDER (ADHD)

Attention Deficit/Hyperactivity defined

Attention Deficit/Hyperactivity Disorder (ADHD) was first described by Sir George F. Still (1902) as a condition persisting in children with a problem associated with “moral control”. The American Academy of Pediatrics (AAP, 1994) defines ADHD as a prevalent and debilitating disorder for which the diagnosis is based on persistent and developmentally inappropriate levels of over-activity, inattention, and impulsivity. The Diagnostic and Statistical Manual of Mental Disorders (DSM) – 5 version defines ADHD by clinical presentation before 12 years of age, with the symptoms of inattention and/or hyperactivity/impulsivity present in 2 or more settings that cannot be better explained by another condition.


Prevalence

ADHD imposes an enormous burden on society in terms of psychologic dysfunction, adverse vocational outcome, and stress on family members of the ADHD patients. A meta-analysis conducted in 2015 suggested there are approximately 129 million children (ages 5 – 19) suffering from ADHD. The Center for Disease Control and Prevention (CDC) provided statistics on ADHD for the year 2016 wherein it was reported that 6 out of 10 children were taking medication for ADHD (which represents 1 in 20 of all the children in the U.S.) for the age group 2 – 17 years. Of that number, 47% of ADHD patients received various behavioral treatments (within one year) and nearly 64% of ADHD patients had comorbidities such as conduct disorder, anxiety, depression, and Tourette syndrome.


Etiopathogenesis

ADHD has a complex etiology with multiple genetic and environmental factors, and the complex interactions between these factors create this spectrum of neurobiological lability. In recent years, the prefrontal cortex (PFC), caudate, and cerebellum areas of the brain have been identified as the primary areas where ADHD presents. The interrelationship among these regions is overly sensitive to the neurochemical environment, maintained by the neurotransmitters (NTs), dopamine (DA), and norepinephrine (NE). ADHD presents with a lower-than-normal density of DA. Most studies on ADHD report a reduction in size of the prefrontal and the precentral areas of the brain in these patients. In addition, in the temporal lobe, the cortical thickness differs significantly in ADHD patients, affecting language abilities, visual perception, multimodal sensory integration, and semantic memory processing. Delayed cortical maturation (at age 3 years, or later) has also been reported in children with ADHD as compared to typically developing children. Individuals with ADHD present with emotional dysregulation, that may arise as deficiencies in orienting towards, recognizing and/or allocating attention to emotional stimuli. ADHD is hypothesized to occur due to a mixture of dominant & recessive major genes with complex polygenic transmission patterns. Twin and family studies on ADHD report a strong heritability (60%-90%). Large, rare, chromosomal deletions and duplications called copy numbers are highly prevalent in ADHD. Polymorphisms of the genes that encode DAD4, DRD4, DAD5, SLC6A3, SNAP-25, HR1B, and DAT-1 receptors cause reduced functionality of the neurotransmitters in ADHD.


Symptoms & Diagnosis

The diagnosis of ADHD requires a psychiatrist/child psychiatrist, pediatrician, or other appropriately qualified, trained, and experienced specialists. The DSM-5 criteria require the symptoms to last for at least 6 months, with 6 or more symptoms, in 2 or more settings (home, school, workplace, extracurricular and/or social activities, etc.) that are inappropriate for the developmental level, and impair academic and/or social progression, and that cannot be better described in any other terminology relating to any other disease/disorder. An altered sensitivity to reward/punishment is also present in patients with ADHD. The symptoms of ADHD in adults include difficulty in concentration, procrastination, hyper-focalization, excessive distractibility, mind-wandering/daydreaming, easily overwhelmed with thoughts not necessarily negative (unlike anxiety). Impulsivity in adult-ADHD is prominent in the verbal sphere.

Individuals with ADHD have difficulty with regulation of their emotions, which is prevalent throughout their lifespan. Emotional dysregulation may arise as deficits in orienting towards, recognizing and/or allocating attention to emotional stimuli. These deficits implicate a dysfunction within striato-amygdalo-medial prefrontal cortical network. A focus on this aspect of ADHD could guide novel therapeutics. The diagnosis of ADHD employs a clinical interview with the parents/family of the patient (who maybe a child/adult), that documents a detailed developmental history including medical or psychiatric antecedents (if any), information on family functioning, behavioral difficulties, and strengths of the patient in peer relationships, school/workplace, and leisure time. In this context, informant rating scales such as the Conner’s Rating Scales – 3rd edition, or the Strengths and Difficulties Questionnaire are useful. Neuroimaging is an adjunctive diagnostic tool for ADHD. Magnetic resonance imaging (MRI) gives a detailed insight into the brain microstructure including gray matter volume, density, cortical thickness, and white matter integrity.


Functional MRI (fMRI) allows recording of physiologic parameters of a functioning brain through activation and connectivity measures with a high-spatial resolution. Studies have also identified several biomarkers for ADHD, in the areas of neurophysiology, neurochemistry, neuroimaging, and genetics. The differential diagnosis for ADHD includes disorders presenting with learning disabilities, speech problems, anxiety, vision and hearing problems, and oppositional defiant disorder (ODD). ADHD may co-exist with mood disorders, impulse control disorders, substance abuse disorders, and sleep disorders.

Treatment

Neuroimaging (MRI & fMRI), Intelligence Quotient (IQ) & other neuropsychologic tests, and Electroencephalogram (EEG) maybe used as adjunct diagnostic tools but are not recommended for routine use. Several national and international guidelines on management of ADHD exist. For pre-school aged children with ADHD, behavioral therapy is the first line of treatment, however, pharmacotherapy is the mainstay of treatment for older children and adults. The FDA-approved drugs for treating ADHD include stimulants – amphetamine & methylphenidate. Additionally, atomoxetine, α-2 agonists, and tricyclic antidepressants (TCAs) are used, off-label to treat ADHD. The non-pharmacologic treatment modalities have demonstrated a considerable success rate in the management of ADHD, especially in pre-school aged children. These comprise: Behavior management interventions (parent-training, classroom intervention, and peer-based intervention); Training interventions (cognitive behavioral therapy/CBT, neurofeedback, virtual- and augmented reality-based training educational games/programs, organizational & skills training); Physiologic interventions (physical exercise, and yoga); Integrative medicine (mindfulness, Tai Chi, hypnosis, dietary intervention, and meditation). Studies report a significant negative impact of ADHD on the quality of life in the affected individuals including both children and adults. However, benefits of early therapeutic intervention in children and pharmacotherapy in adults have been proven to improve the quality of life of ADHD patients.


Written By: Manasa Tata, M.D.S. & Lawrence D. Jones, Ph.D