Attention Deficit Hyperactivity Disorder

Attention deficit hyperactivity disorder is a neurodevelopmental disorder characterized by a pattern of inattention and/or hyperactivity-impulsivity that occurs in at least 2 different settings for more than 6 months. Although the patient has normal intelligence, the disease causes functional decline. The onset usually occurs before 12 years of age and often persists into adulthood. The 1st line of treatment is stimulant medications but may include non-stimulant medications and behavioral therapy.

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Overview

Definition

Attention-deficit hyperactivity disorder is a neuropsychiatric condition marked by a pattern of decreased attention and hyperactivity or impulsivity.

Epidemiology

  • Affects about 8%–12% of children 
  • 70% will carry the disease into adolescence and 50% into adulthood.
  • Prevalence in adulthood is 4%–5%.
  • Male:female prevalence: 5:1 
  • Risk factors:
    • 1st-degree relative who had a similar disease
    • Exposure to lead in early childhood
    • Maternal exposure to drugs, alcohol, or cigarette smoke
    • Premature birth and associated perinatal hypoxic injury
    • Acquired traumatic brain injury
    • Environmental risk factors: 
      • Low socioeconomic status
      • Parental mental disorder

Classification

Major subtypes:

  • Predominantly inattentive:
    • Most common among girls
    • Deficient in attention to activities
    • Disorganized 
    • Leave tasks rapidly
    • Lack of focus
    • Don’t follow instructions
  • Predominantly hyperactive/impulsive:
    • Most common among boys
    • Restless or fidgety (nervous)
    • Impulsive
    • Talk a lot and are disruptive
  • Combined:
    • Most common form
    • Variety of symptoms from both inattentiveness and impulsivity

Etiology and Pathophysiology

Etiology

  • Genetics and mutations: 
    • Children born to affected parent have 2x–8x risk of developing the disease.
    • 55%–90% monozygotic twin concordance
    • Possible genetic mutations in dopamine receptors (DRD4, DRD5, DAT, DRH, 5-HTT, and 5 HTR1B)
    • Genetic syndromes with increased risk: 
      • Klinefelter syndrome
      • Turner syndrome
      • Fragile X syndrome
      • Neurofibromatosis type 1
      • Williams syndrome
      • DiGeorge syndrome
  • Neurotransmitter deficiency: 
    • Decrease in dopamine and norepinephrine in areas of the brain responsible for attention and control of activity and behavior (frontal and prefrontal cortex)
    • Supported by positive response to stimulant medications and functional magnetic resonance imaging (fMRI) studies showing reduced neurotransmission in these areas
  • Structural brain changes:
    • Changes in areas that control attention, behavior, and emotions (basal ganglia and cerebellum): smaller anterior cingulate gyrus and dorsolateral prefrontal cortex 
    • May be due to perinatal hypoxic-ischemic injury that destroys converging glutaminergic neurons, or fetal circulatory insufficiency

Pathophysiology

  • Exact pathophysiology is unknown.
  • Associated with functional and cognitive deficits related to structural changes in brain:
    • Areas of brain involved include frontal cortex, subcortical structures, and anterior cingulate gyrus.
  • Involves dysregulation of dopamine and norepinephrine in brain

Clinical Presentation

Differs depending on age of child:  

  • Preschool:
    • Hyperactive
    • Impulsive
    • Inflexible
    • May be aggressive with peers
    • Decreased sleep 
  • Elementary school: 
    • Struggles with listening in class
    • Poor organizational skills
    • Struggles with social interaction
    • Difficulty functioning independently
  • Adolescence:
    • Academic demands become overwhelming.
    • Struggles with attention, learning, executive functioning

Diagnosis

Symptoms

  • Onset of symptoms before the age of 12
  • Symptoms occur in 2 or more settings, e.g., school, home, or work.
  • Duration: > 6 months 
  • Symptoms should cause decline in function or development.

Symptoms of inattention:

Six or more of the following symptoms in childhood (5 symptoms sufficient in adolescents and adults):

  • Lack of attention to details, repeatedly making careless mistakes
  • Inability to focus or remain on task
  • Inattention when spoken to
  • Inability to follow instructions and failing to finish work on time
  • Disorganization in completing tasks
  • Avoidance of tasks that require continuous mental effort or attention (e.g., homework)
  • Frequent misplacement and loss of personal things (e.g., pencil, books)
  • Frequently forgetting to complete daily activities

Symptoms of hyperactivity and impulsivity:

Six or more of the following symptoms in childhood (5 symptoms sufficient in adolescents and adults):

  • Fidgeting and restlessness  
  • Leaving seat in situations where remaining seated is expected (e.g., in classroom)
  • Running or climbing in inappropriate situations
  • Difficulty engaging in activities
  • Uncomfortable with remaining still (often “on the go,” acting as if “driven by a motor”)
  • Excessive talking 
  • Excessive outbursts (shouting out answers before completion of question)
  • Difficulty standing in line or waiting their turn
  • Often interrupts others

Mental status and physical exam

  • Children with hyperactivity are more likely to be referred for evaluation than those with the inattentive type. 
  • Obtaining interviews from teachers as well as school reports is critical.
  • History taking should include detailed records from parents to screen for risk factors, e.g., substance use or their own symptoms of ADHD.
  • Initial clinical evaluation should include height/weight, blood pressure, and pulse. 
  • Validated rating scale, such as Vanderbilt ADHD rating scale, may be used to assist with diagnosis.

Exclusion of other causes

Rule out other potential causes for abnormal behavior.

  • Symptoms due to other psychiatric disorder: 
    • Oppositional defiant disorder (ODD)
    • Schizophrenia
    • Major depressive disorder
    • Bipolar disorder
    • Anxiety disorder
    • Tourette syndrome
    • Dissociative disorder
    • Personality disorder
    • Substance intoxication or withdrawal
  • Screen for specific learning disability to ensure that symptoms are not due to failure to understand tasks or instructions.
  • For those with inattentive symptoms, evaluation for petit mal epilepsy is recommended. 
  • Neuroimaging is not recommended or required for diagnosis. 

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Management

Pharmacotherapy

  • Stimulant medication: 
    • 1st-line therapy in school-aged children
    • More effective than non-stimulant
    • Includes: methylphenidate, amphetamines 
    • Mechanism of action: 
      • Blockage of dopamine and norepinephrine transporters 
      • Reduction of monoamine oxidase activity 
    • Preparations with sustained release are preferred due to less of a need for interruptions for medications, as well as avoiding periods of rebound or irritability. 
    • Side effects:
      • Decreased appetite, insomnia, headache
      • Potentially significant increases in blood pressure and/or heart rate
      • Modest stunting in growth 
      • May exacerbate comorbid tics 
      • Has potential for misuse
      • Recommend obtaining electrocardiogram prior to start, especially for patients with personal or family history of cardiovascular disease 
  • Non-stimulant medications:  
    • No potential for misuse and do not cause euphoria, unlike psychostimulants 
    • Atomoxetine:
      • Usually 2nd-line therapy 
      • Mechanism of action via norepinephrine reuptake inhibitor 
      • Indicated with comorbid anxiety, tic disorder, or insomnia 
      • Side effects: increased suicidal ideation in children 
    • Alpha agonists: 
      • Include: guanfacine, clonidine
      • Efficacy significantly lower than psychostimulants 
      • Used if patients cannot tolerate stimulants or develop new-onset tics
      • Side effects: drowsiness, dizziness, headache
  • Antidepressants: 
    • 3rd-line therapy
    • May be used for adults with comorbid substance use or mood disorders
    • Bupropion commonly used

Psychotherapy

  • 1st-line treatment for preschool-aged children (4–5 years of age) 
  • Involves education for family/teachers, as well as patient, to reach short- and long-term goals 
  • Educational accommodation can be helpful in terms of academic performance.
  • Psychotherapy supplements, but may not replace, medication therapy.

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Differential Diagnosis

  • Specific learning disorder: neurodevelopmental disorder with both environmental and genetic factors that causes an impairment of the brain’s ability to perceive or process either verbal or nonverbal information. The disorder is an umbrella of diagnoses that includes academic difficulties in domains such as reading, writing, and mathematics. Specific learning disorders may be present alongside ADHD. Key difference from ADHD is a lack of inattention or hyperactivity. 
  • ODD: Continuous pattern of angry/irritable mood, argumentative/defiant behavior, or vindictiveness that is present for at least 6 months. The diagnosis is frequently found in those with ADHD. While ADHD is present in numerous settings and among peers, symptoms of ODD are mostly directed toward authority figures, such as parents or teachers.  
  • Major depressive disorder (MDD): a mood disorder marked by depressed mood, sleep disturbance, anhedonia, feelings of guilt or worthlessness, loss of energy, reduced ability to concentrate, weight or appetite changes, psychomotor retardation or agitation, and suicidal ideation. While the decrease in concentration overlaps in both diagnoses, ADHD is distinguished from MDD by the lack of other depressive mood features.

References

  1. Krull, K. (2020). Attention deficit hyperactivity disorder in children and adolescents: overview of treatment and prognosis. UpToDate. Retrieved May 5, 2021, from https://www.uptodate.com/contents/attention-deficit-hyperactivity-disorder-in-children-and-adolescents-overview-of-treatment-and-prognosis
  2. Magnus W, Nazir S, Anilkumar AC, et al. Attention Deficit Hyperactivity Disorder. [Updated May 4, 2021]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021. https://www.ncbi.nlm.nih.gov/books/NBK441838/
  3. Sadock BJ, Sadock VA, Ruiz, P. (2014). Kaplan and Sadock’s synopsis of psychiatry: Behavioral sciences/clinical psychiatry (11th ed.). Chapter 31, Child psychiatry, pages 1169-1181. Philadelphia, PA: Lippincott Williams and Wilkins.

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