attention-deficit hyperactivity disorder. adhd statistics 3-5% of all u.s. school-age children are...
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ADHD Statistics
3-5% of all U.S. school-age children are estimated to have this disorder.
5-10% of the entire U.S. population
Males are 3 to 6 times more likely to have ADHD than are females.
At least 50% of ADHD sufferers have another diagnosable mental disorder.
ADHD: Etiology
ADHD is a heterogeneous behavioral disorder with multiple possible etiologies
ADHD
NeuroanatomicNeuroanatomicNeurochemicalNeurochemical
CNS CNS insultsinsults
Genetic Genetic originsorigins
Environmental Environmental factorsfactors
History of ADHDMid-1800s: Minimal Brain Damage
Mid 1900s: Minimal Brain Dysfunction
1960s: Hyperkinesia
1980: Attention-Deficit DisorderWith or Without Hyperactivity
1987: Attention Deficit Hyperactivity Disorder
1994-present: ADHD
Primarily Inattentive
Primarily Hyperactive
Combined Type
What is ADHD?
“The unifying abstraction that currently best encompasses the faculties principally affected in ADHD has been termed executive function (EF), which is an evolving concept…there is now impressive empirical support for its importance in ADHD”
– Castellanos FX. (1999) The psychobiology of attention-deficit/hyperactivity disorder. In HC Quay, AE Hogan (Eds), Handbook of Disruptive Behavior (pp. 179-198). Kluwer Academic
Executive Functions
Wide range of central control processes of the brain
Connect, prioritize and integrate cognitive functions – moment by moment
Like a conductor of a symphony orchestra
“Focus” and Executive Functioning
Intention symptoms in the DSM-IV – Do not mean
• Unable to focus…as in holding the camera still to take a photo of an unmoving object
– Do mean• Unable to focus…as in focusing on the task of
driving a car.
Development of Brain Structures that Support EF
Structures and functions that support EF are not fully developed at birth
Neural networks underlying EF control begin at 2-4 years of age, but don’t fully develop until the 20’s.
Development of EF capacities continues into early adulthood.
Continuing Brain Development in Late Childhood and Adolescence
6-15 years of age: extreme growth (80%) occurs at the collosal isthmus that supports associative relay, while considerable synaptic pruning occurs
Brain myelination increases 100% during the teenage years
Dopamine (DA), norepinephrine (NE) and Serotonin (5-HT) transmitter systems in the brain continue to develop into one’s 20’s
EF: Development & Demands
EF capacity develops through childhood/teens to adulthood – it is not totally present in early childhood.
Environmental demands for EF increase with age
EF impairments are frequently unnoticeable by age 7
How can EF become impaired?
Developmentally (eg, ADHD etc.) Trauma (eg, TBI) Disease (eg, Alheimer’s) In trauma & disease, the patient usually
has adequate EF, then loses it. In ADHD, EF has not developed
adequately.
Diagnosing ADHD: DSM-IV Inattentiveness:
Has a minimum of 6 symptoms regularly for the past six months.
Symptoms are present at abnormal levels for stage of development
Lacks attention to detail; makes careless mistakes
has difficulty sustaining attention
doesn’t seem to listen
fails to follow through/fails to finish projects
has difficulty organizing tasks
avoids tasks requiring mental effort
often loses items necessary for completing a task
easily distracted
is forgetful in daily activities
Diagnosing ADHD: DSM-IV
Hyperactivity/ Impulsivity:
Fidgets or squirms excessively
leaves seat when inappropriate
runs about/climbs extensively when inappropriate
has difficulty playing quietly
often “on the go” or “driven by a motor”
talks excessively
blurts out answers before question is finished
cannot await turn
interrupts or intrudes on others
Has a minimum of 6 symptoms regularly for the past six months.
Symptoms are present at abnormal levels for stage of development
Diagnosing ADHD: DSM-IV
Additional Criteria:
Symptoms causing impairment present before age 7
Impairment from symptoms occurs in two or more settings
Clear evidence of significant impairment (social, academic, etc.)
Symptoms not better accounted for by another mental disorder
Problems of Diagnosis
Subjectivity of Criteria
Inconsistent evaluations--presence of symptoms usually given by teacher or parent
Study by Szatmari et al (1989) showed that the number of diagnosed cases of ADHD decreased 80% when observations of parent, teacher and physician were used rather than just one source
Symptoms in females more subtle---leads to underdiagnosis
ADHD and the BrainDiminished arousal of the Nervous System
Decreased blood flow to prefrontal cortex and pathways connecting to limbic system (caudate nucleus and striatum)
PET scan shows decreased glucose metabolism throughout brain Comparison of normal brain (left) and brain
of ADHD patient.
ADHD and the Brain IISimilarities of ADHD symptoms to those from injuries and lesions of frontal lobe and prefrontal cortex
MRIs of ADHD patients show:Smaller anterior right frontal lobe
abnormal development in the frontal and striatal regions
Significantly smaller splenium of corpus callosumdecreased communication and processing of information between hemispheres
Smaller caudate nucleus
What causes ADHD?Underlying cause of these differences is still unknown; there is much conflicting data between studiesStrong evidence of genetic componentPredominant theory: Catecholamine neurotransmitter dysfunction or imbalance
decreased dopamine and/or norepinephrine uptake in braintheory supported by positive response to stimulant treatment
Recent study indicates possible lack of serotonin as a factor in mice
Genetic Linkages to ADHD
Twin studies by Stevenson, Levy et al, and Sherman et al indicate an average heritability factor of .80Biederman et al reported a 57% risk to offspring if one parent has ADHD. Dopamine genes
DA type 2 geneDA transporter gene (DAT1)Dopamine receptor (DRD4, “repeater gene”) is over-represented in ADHD patients
DRD4
DRD4 is most likely contributor
DRD4 affects the post-synaptic sensitivity in the prefrontal and frontal cortex
This region of cortex affects executive functions and attention
Executive functions include working memory, internalization of speech, emotions, motivation, and learning of behavior
TreatmentCounseling of individual and family
Stimulants
Tricyclic antidepressants
Bupropion
Clonidine
SSRIs
Sedating Antihistamines
Benzodiazepines
-SNRI – atomoxetine HCL (Strattera)
StimulantsExact mechanism unknown
Raise activity level of the CNS by decreasing fluctuations of activity or lowering threshold needed for arousal
Similar in structure to NE and DA, and may mimic their actions
At least 75% have positive response with single dose
95% respond well to stimulant treatment
Include methylphenidate, dextroamphetamine, amphetamine-dextroamphetamine and pemoline
Methylphenidate
Is a piperidine derivative commonly known as Ritalin®
Is believed to act as dopamine agonist in synaptic cleft
Stimulates frontal-striatal regions
Dosage (5-20 mg) must be adjusted to each patient
Taken orally, 2-3 times a day as needed
Behavioral effects start within 1/2 hour to hour after ingestion, peaking at 1 and 3 hours
Also comes in Sustained-Release forms:
Concerta
Metadate
Effects of MPHElevates mood
Raises arousal of CNS and cerebral blood flow
Increases productivity
Improves social interactions
Increases heart rate and blood pressure
Side EffectsCommon:
decreased appetiteinsomniabehavioral reboundhead and stomach aches
Also thought to cause temporary height and weight suppression
Mild:anxiety/ depressionirritability
Rare:tics (Tourette’s Syndrome)overfocussingliver problems or rash (Pemoline only)
Storagevesicle
DA Transporter
Cytoplasmic DA
Methylphenidateinhibits
Presynaptic Neuron
Synapse
Probable Mechanism of Action of Methylphenidate
Wilens and Spencer. Handbook of Substance Abuse: Neurobehavioral Pharmacology. 1998;501-513.
Neurotransmitters
CH2 CH2 NH2OH
OH
DopamineDopamineOH
CH CH NH2OH
OH
NorepinephrineNorepinephrine
CH2 CH NH2
CH3
AmphetamineAmphetamine
O
NH2
N
O
PemolinePemolineMethylphenidateMethylphenidate
COCH3
O
NH
MRI in Adults with ADHD
MGH-NMR Center & Harvard- MIT CITP
Bush G, et al. Biol Psychiatry. 1999;45(12):1542-1552.
Neurotransmitters
CH2 CH2 NH2OH
OH
DopamineDopamineOH
CH CH NH2OH
OH
NorepinephrineNorepinephrine
CH2 CH NH2
CH3
AmphetamineAmphetamine
O
NH2
N
O
PemolinePemolineMethylphenidateMethylphenidate
COCH3
O
NH
The Mechanisms of Action of AmphetamineThe Mechanisms of Action of AmphetamineWilens and Spencer. Handbook of Substance Abuse: Neurobehavioral Pharmacology. 1998;501-513.
AMPH Inhibits
AMPH is taken up into cell causing DA release into synapse
AMPH diffuses intovesicle causing DA release into cytoplasm
Presynaptic Neuron
Storagevesicle
DA TransporterProtein
Cytoplasmic DA
AMPH
AMPH
Synapse
AMPH blocks uptake into vesicle
Dopamine Neurotransmission Relative to ADHD
Enhances signal Improves attention
– Focus– On-task behavior– On-task cognition
Solanto. Stimulant Drugs and ADHD. Oxford; 2001.
Nigrostriatal Pathway
Mesolimbic Pathway
Substantia nigra
Ventral tegmental area
Mesocortical Pathway
DopamineDopamine
Locus Ceruleus
Frontal
Limbic
Norepinephrine Neurotransmission Relative to ADHD
• Dampens noise
• Executive operations
• Increases inhibition
Solanto. Stimulant Drugs and ADHD. Oxford; 2001.
NorepinephrineNorepinephrine
Catecholaminergic Neurotransmission Relative to ADHD
Striatal - Prefrontal Enhances Signal Improves Attention
– Focus– Vigilance– Acquisition – On-task behavior– On-task cognitive– Perception(?)
Prefrontal Dampens Noise
– Distractibility– Shifting
Executive operations Increases Inhibition
– Behavioral– Cognitive– Motoric
NorepinephrineNorepinephrineDopamineDopamine
Solanto. Stimulant Drugs and ADHD. Oxford; 2001.
MRI in Adults with ADHD
MGH-NMR Center & Harvard- MIT CITP
Bush G, et al. Biol Psychiatry. 1999;45(12):1542-1552.
Atomoxetine HCl
Strattera has recently been approved by the FDA as the only non-stimulant first line treatment for ADHD.
blocks norepinephrine transporter, especially in frontal lobes
no insomnia though some reduced weight gain with growth in first 12 months of use
non-controlled
Outcome ADHD can persist into adulthood, but usually symptoms
gradually diminish When it persists into adulthood, it usually requires ongoing
treatment and counseling most will develop another disorder (especially learning disability,
ODD, depression, and/or conduct disorder) Without treatment:
antisocial and deviant behavior increased rates of divorce, moving violations, incarceration,
and institutionalization