Attention-Deficit/Hyperactivity Disorder (ADHD) Andrea Chronis-Tuscano, Ph.D. Associate Professor of Psychology Director, Maryland ADHD Program University of Maryland

Maryland ADHD Program Mission To conduct clinical research that advances our knowledge about the assessment and treatment of ADHD To provide comprehensive, evidence-based assessment and treatment of ADHD and associated problems to children and their families To train the next generation of clinical psychologists in evidence-based assessment and treatment practices To educate parents, schools, health professionals and the community about evidence-based assessment and treatment for ADHD

Overview Definition & Features Etiological Factors Evidence-Based Assessment & Treatment Professional Practice Parameters

Prevalence & Impact Prevalence rate of 6-10% More prevalent in males than females Male:female ratio is 3:1 in epidemiological samples Ranges from 3:1 - 9:1 in clinical samples 50% of children referred to mental health clinics are referred for ADHD-related problems Annual societal cost of illness for ADHD estimated to be between $36 - 52 billion $12,005 -- $17,458 annually per individual www.cdc.gov

Definition & Features

DSM-IV Diagnostic Criteria Inattention Symptoms (at least 6 symptoms required) Fails to give close attention to details or makes careless mistakes in schoolwork, work, etc. Difficulty sustaining attention Does not seem to listen when spoken to directly Does not follow through on instructions and fails to finish schoolwork, chores, etc. Difficulty organizing tasks and activities Avoids tasks requiring sustained mental effort Loses things necessary for tasks or activities Easily distracted by extraneous stimuli Forgetful in daily activities Primary deficit in ADHD is sustained attention, particularly for repetitive, structured, and uninteresting tasks. Attention problems may be in alerting and preparing for the task from the outset, as well as, the ability to sustain attention. Variety of “attention deficits” – attentional capacity, selective attention (DISTRACTABILITY), and sustained attention. APA, 2000

ADHD Diagnostic Criteria (cont.) Hyperactivity-Impulsivity Symptoms (at least 6 symptoms required) Difficulty playing or engaging in activities quietly Always "on the go" or acts as if "driven by a motor” Talks excessively Blurts out answers Difficulty waiting in lines or awaiting turn Interrupts or intrudes on others Runs about or climbs inappropriately Fidgets with hands or feet or squirms in seat Leaves seat in classroom or in other situations in which remaining seated is expected Some have suggested that both hyperactivity and impulsivity part of a more fundamental deficit in behavioral regulation. Hyperactive-impulsive behavior is activity that is excessively intense, inappropriate, and NOT GOAL DIRECTED. Impulsivity – difficulty stopping ongoing behavior, difficulty awaiting turn, inability to resist immediate gratification (DELAY AVERSION), and interrupting others’ conversations APA, 2000

ADHD Diagnostic Criteria (cont.) Symptoms present before age 7 Clinically significant impairment in social or academic/occupational functioning Some symptoms that cause impairment are present in 2 or more settings (e.g., school/work, home, recreational settings) Not due to another disorder (e.g., Autism, Mood Disorder, Anxiety Disorder) APA, 2000

Subtypes Combined Type Predominantly Inattentive Subtype Clinical levels of both inattention and hyperactivity/impulsivity Most common subtype Predominantly Inattentive Subtype Clinical levels of inattention only Often not identified until middle school Sluggish cognitive tempo Predominantly Hyperactive/Impulsive Subtype Clinical levels of hyperactivity/impulsivity only More common among very young children prior to school entry Predominately inattentive type – frequently described as drowsy, confused, “in a fog”. May be comorbid with learning disorders, slow processing speed, difficulties with information retrieval, anxiety, and mood disorder. Some debate as to whether this should be thought of as a separate disorder.

Controversial Issues with DSM-IV Criteria Developmentally insensitive Symptoms based on field trials conducted with elementary school aged boys (Lahey et al., 1994) Categorical (not continuous) view Requirement of onset before age 7 arbitrary Requirement of 6 months duration too brief Requirement that symptoms be demonstrated across 2 settings

Associated Problems Peer problems Family dysfunction/parental issues Inattentive symptoms  ignored Hyperactive/impulsive symptoms  actively rejected Not deficient in social reasoning/understanding, but rather the execution of appropriate social behavior Family dysfunction/parental issues No clear causal relationship between family problems and ADHD Family problems can impact the severity and developmental course/outcomes of ADHD Self-esteem Inflated: Positive illusory bias (Hoza) Low self esteem associated with comorbid depression There are some other problems that are associated with (but not caused by ADHD). Also, every child with ADHD is different and may have any combination of these difficulties or none of them. As I just mentioned, they may have difficulties making and keeping friends. This is particularly important as peer relationships are an important predictor of relationships with adults. Children with poor peer relationships are more likely to have poor relationships as adults. Children with ADHD often come from families where there is more stress or parents may have ADHD themselves. Due to the impairment caused by their symptoms, children with ADHD often don’t feel very good about themselves. I work part-time at Children’s National Medical Center and just last week I heard a child being tested in the room next door to where I was testing a child. This child was yelling, “I can’t do it. I always fail.” These thoughts are not uncommon in children with ADHD. Fifty percent of children with ADHD also have oppositional or aggressive difficulties. They may be arguing with adults often or misinterpreting something a peer does as hostile and impulsively hitting them when they feel threatened.

Developmental Course ADHD is persistent across lifespan in most cases Methodological issues impact estimates of persistence ADHD severity, psychiatric comorbidity, and parental psychopathology predict persistence (Biederman et al., 2011) Inattention remains stable; hyperactivity declines with age DSM-IV criteria may not capture adolescent/adult manifestations of impulsivity Adult outcomes including psychiatric comorbidity When ADHD co-occurs with conduct disorder, chronic criminality and serious substance use can result When ADHD co-occurs with depression, risk of suicide Probable that ADHD is present at birth, but difficult to identify in infancy; hyperactivity-impulsivity usually appears first. Onset often in preschool years, but usually by school age. Deficits in attention increase as school demands increase. In early school years oppositional and socially aggressive behaviors often develop.Most children still have ADHD as teens, although hyperactive-impulsive behaviors decrease. Problems often continue into adulthood – those adults with ADHD may experience a great deal of boredom, work difficulties, impaired social relations, depression, low self-concept, and substance abuse Better outcomes for youth with less severe symptoms, support, supervision, and access to resources

Etiological Factors

Etiological Factors Average heritability of .80 - .85 Environmental factors are not the cause, but may contribute to the expression, severity, course, and comorbid conditions Dysfunction in prefrontal lobes Involved in inhibition, executive functions Genes involved in dopamine regulation Dopamine transporter (DAT1) gene implicated 7 repeat of dopamine receptor gene (DRD4) implicated Gene x environment interactions Possible differences in size of brain structures Prefrontal cortex, Corpus callosum, caudate nucleus Abnormal brain activation during attention & inhibition tasks Kieling, Gondaves. Tannock. & Castellanos. 2008; Mick &. Faraone, 2008

Brain Structure & Function Differences in brain maturation, structure, function (particularly abnormalities in frontostriatal circuitry): Prefrontal cortex Basal ganglia Cerebellum These areas of the brain are associated with executive function abilities: Attention, spatial working memory, and short-term memory Response inhibition and set shifting Specific brain findings (neuro-imaging studies): --Neuro-imaging studies suggest the importance of the frontostriatal region of the brain in ADHD and the pathways connecting this region with the limbic system (via the striatum) and the cerebellum. --Children with ADHD have smaller right prefrontal cortex, structural abnormalities in areas of the basal ganglia (e.g., caudate nucleus), smaller total and right cerebral volumes, smaller cerebellum, and delay in brain maturation in the prefrontal cortex (children with ADHD lag 2-3 years behind children without ADHD in development of the PFC). Attention = the ability to focus or filter information, including attentional alerting and sustained attention. Memory = the ability to hold information in mind (spatial refers to how things are ordered in space relative to one another), which depends on attention. Response inhibition = the ability to interrupt a response during dynamic moment-to-moment behavior (i.e., maintaining focused behavior requires continually suppressing alternate behaviors that may be activated by context). *Most well-studied executive function skill in ADHD. Set shifting = The ability to shift one’s mental focus within a task such as sorting by color vs. sorting by number (i.e., task switching). **Note that spatial working memory and response inhibition are the most researched, and have moderate to large effect sizes (i.e., differences between ADHD kids and non-ADHD kids in spatial working memory and response inhibition are moderate to large).

Neurotransmitters Neurotransmitter differences, particularly in levels of: Dopamine Norepinephrine Epinephrine Serotonin Dopamine has been associated with approach and pleasure-seeking behaviors Norepinephrine plays a role in emotional/behavioral regulation Most research evidence suggests deficiencies in the availability of dopamine and norepinephrine among children with ADHD relative to comparison children, although epinephrine and serotonin have also been implicated.

Executive Functioning Deficits Cognitive processes which activate, integrate, and manage other brain functions Examples: Cognitive: working memory, planning, use of organizational strategies Language: verbal fluency, communication Motor: response inhibition, motor coordination Emotional: self-regulation of emotion, frustration tolerance But… EF deficits overlap with ADHD symptoms EF deficits are not unique to ADHD Not all children with ADHD have EF deficits

Barkley’s Theory “ADHD is not a problem with knowing what to do; it is a problem of doing what you know.” -Barkley, 2006 Behavioral disinhibition is the basis of executive functioning deficits in ADHD A performance, rather than knowledge, deficit

A Possible Developmental Pathway for ADHD From Mash & Wolfe, 2007

Evidence-Based Assessment & Treatment of ADHD

Evidence-Based Assessment Teacher- and parent-completed questionnaires Structured clinical interview with parent(s) IQ/Achievement testing to screen for learning disabilities (50% comorbidity) Behavioral observations at home and school No medical screen, cognitive test, or brain imaging technique can detect ADHD Children with ADHD can focus long enough to watch TV, play videogames or sit still at the doctor’s office. How do children get assessed for ADHD? Well, when they present to a professional, they should receive a comprehensive, evidence-based assessment. scales are often used to compare children to the norm. A clinical interview with parents is another way to clarify particular concerns that a parent may have or to follow-up on information gathered on these questionnaires. Also, many children with low IQs or learning disabilities have difficulty achieving at grade level, so IQ/Achievement testing is often part of a comprehensive assessment for ADHD. ADHD and learning disabilities co-occur frequently, so many children with ADHD have disorder of written expression or a math LD. Finally, behavioral observations are a very useful clinical tool in that we can see how a child performs in a one-on-one very structured situation with a lot of consistent praise and direct commands as well as the parent-child and teacher-child interaction. Pelham, Fabiano & Massetti, 2005

Well-Established ADHD Treatments Stimulant Medications Behavioral Interventions Behavioral parent training Behavioral classroom management Intensive summer treatment programs Pelham & Fabiano, 2008

Medication: Stimulants Most well-researched, effective, and commonly used medication treatment for ADHD. Methylphenidate (Ritalin, Concerta, and Metadate) Dextroamphetamine (Adderall) These medications reduce ADHD symptoms by: Blocking the reuptake of norepinephrine (NOR) and dopamine (DOP) and facilitating their release  Enhances NOR and DOP availability in in certain brain regions: PFC and basal ganglia Stimulants work by increasing norepinephrine and dopamine actions by blocking their reuptake and facilitating their release. This leads to enhancement of norepinephrine and dopamine in certain brain regions including the prefrontal cortex and basal ganglia.

Stimulant Medications Research has shown that stimulants: Are highly effective in reducing ADHD symptoms in the short term Decrease disruption in the classroom Increase academic productivity and on-task behavior Improve teacher ratings of behavior Different formulations work best for different children Common side effects: insomnia, decreased appetite Strattera (atomoxetine) A non-stimulant alternative that works well for some children Has not been studied as long or as intensively as the stimulants Smaller effect size relative to the stimulants

Limitations of Stimulant Treatment Individual differences in response Not all children respond (approximately 80%) Limited impact on domains of functional impairment Primary reason for treatment seeking Does not normalize behavior Family problems beyond the scope of medication No long-term effects established Long-term use rare Limited parent/teacher satisfaction Some families are not willing to try medication

How do we identify evidence-based, non-pharmacological treatments?

“Evidence-based treatment” implies that studies have been conducted with the following features: Careful specification of the target population Diagnostic, demographic, recruitment, selection Random assignment to conditions Comparison could be to placebo but ideally to established tx Use of treatment manuals Ensures reliability of administration and facilitates replication Multiple outcome measures with blind raters Statistically significant differences between the tx and comparison group at post-tx Replication, ideally by independent researchers Chambless et al., 1996; Silverman & Hinshaw, 2008

Well-Established Non-Pharmacological Treatments Behavioral parent training 33 well-conducted studies Behavioral classroom management 45 well-conducted studies Pelham, Wheeler & Chronis, 1998; Pelham & Fabiano, 2008

Behavioral Treatment Components Psychoeducation about ADHD Structure/routines Clear rules/expectations Attending/rewards Planned ignoring Effective commands Time out/loss of privileges Point/token systems Daily school-home report card Intensive summer treatment programs

Behavioral Treatment Considerations Need to address cross-situational impairments Poor generalization from treatment setting to real-world Implement treatments in all settings in which child shows impairment School behavior 504 Plan/Individualized Education Plan (IEP) Academic interventions needed in addition to behavioral interventions (Raggi & Chronis, 2006) Environmental contingencies must be delivered consistently, which is difficult to maintain Parental psychopathology can interfere with implementation

Multi-Modal Treatment Study for ADHD (MTA) 6 sites 579 Children, 7-9 y/o ADHD, Combined Type Assigned to 14 months of: Med management Intensive Behavior Therapy Combined treatment Treatment as Usual in the Community (TAU) 2/3 received medication MTA Cooperative Group, 1999

Overall Results All groups showed reductions in ADHD sx over time On primary outcome measure (ADHD sx), medication alone and combined tx did better than behavioral tx alone and tx as usual (TAU) in the community On many measures, combined tx was not significantly better than medication alone Only combined tx was better than TAU on oppositional symptoms, aggression, depression/anxiety symptoms, social skills, parent-child relationship, and reading achievement Higher medication doses were needed in the medication only group relative to the combined treatment group MTA Cooperative Group, 1999

Combined Treatment was superior in terms of: Parent and teacher satisfaction with treatment Normalization of child behavior Improvements in functional outcomes Family interactions Peer relationships Academic functioning Connors et al., 2001; Hinshaw et al., 2000; Pelham et al., 2004; Swanson et al., 2001; Wells et al., 2006

MTA 6-8 Year Follow-Up Original treatment assignment not associated with any of the 24 outcomes 6-8 yrs later ADHD symptom trajectory in the first 3 years predicted 55% of the outcomes Children with the best initial tx response and most favorable clinical presentation at baseline fared best over time Children with behavioral and sociodemographic advantage, with the best response to any tx, had the best long-term prognosis As a group, children with combined-type ADHD exhibit significant impairment in adolescence (on 9 of 21 measures) This suggests a need for sustained treatment over the long term Molina et al., 2009

Practice Parameters

American Medical Association (AMA) “encourages the use of individualized therapeutic approaches…which may include pharmacotherapy, psychoeducation, behavioral therapy, school-based and other environmental interventions, and psychotherapy, as indicated by clinical circumstances and family preferences.” (p.1106)” American Academy of Pediatrics (AAP) “the clinician should recommend medication (strength of evidence: good) and/or behavior therapy (strength of evidence: fair), as appropriate, to improve target outcomes in children with ADHD (strength of recommendation: strong)” (p. 1037)

American Academy of Child & Adolescent Psychiatry (AACAP) Treatment “may consist of pharmacological and/or behavior therapy” but that “pharmacological intervention for ADHD is more effective than a behavioral treatment alone” and that “behavioral intervention alone might be recommended as an initial treatment if the patient’s ADHD symptoms are mild with minimal impairment…or parents reject medication” (p.902)…”if a child has a robust response and shows normative functioning…then psychopharmacological treatment alone is satisfactory” (p. 912)… If the child does not show a robust response to all FDA-approved medications, the clinician should “consider behavior therapy and/or the use of medications not approved by the FDA for treatment of ADHD” (p.907)

Summary ADHD is a highly prevalent, brain-based disorder which is associated with lifelong impairment in functioning Environmental factors can contribute to the expression, severity, course, and comorbid conditions Long-term developmental outcomes for individuals with ADHD can include serious substance abuse, chronic criminality, depression and suicide Stimulant medications and behavior therapy are currently the only established evidence-based treatments for ADHD Combined behavioral-pharmacological treatment has the greatest impact on functional outcomes, is preferred by parents and teachers, and is most likely to result in normalization of behavior