Attention-Deficit Hyperactivity

Disorder

By
Chris Golner

April 19, 1999

Biochemistry/Molecular Biology Seminar
 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.
 Outline
History of ADHD
Symptoms and Diagnosis: DSM-IV criteria
Possible causes
Treatments
Stimulants

Outcome
 History of ADHD
Mid-1800s: Minimal Brain Damage
Mid 1900s: Minimal Brain Dysfunction
1960s: Hyperkinesia
1980: Attention-Deficit Disorder
 With or Without Hyperactivity

1987: Attention Deficit Hyperactivity Disorder

1994-present: ADHD
 Primarily Inattentive
 Primarily Hyperactive
 Combined Type
 Diagnosing ADHD: DSM-IV
 Lacks attention to detail;
makes careless mistakes
 Inattentiveness:  has difficulty sustaining
attention
 doesn’t seem to listen
Has a minimum of 6
 fails to follow through/fails
symptoms regularly for to finish projects
the past six months.  has difficulty organizing
tasks
Symptoms are present at  avoids tasks requiring
mental effort
abnormal levels for stage
 often loses items necessary
of development
for completing a task
 easily distracted
 is forgetful in daily activities
 Diagnosing ADHD: DSM-IV
Hyperactivity/
Impulsivity:
Has a minimum of 6
symptoms regularly for the
past six months.
Symptoms are present at
abnormal levels for stage of
development
 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
 Diagnosing ADHD: DSM-IV
 Symptoms causing impairment
Additional present before age 7
Criteria:  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 Brain
Diminished arousal of
the Nervous System
Decreased blood flow
to prefrontal cortex
and pathways
connecting to limbic
system (caudate
nucleus and striatum)
PET scan shows
Comparison of normal brain (left) and brain
decreased glucose of ADHD patient.
metabolism
throughout brain
 ADHD and the Brain II
Similarities 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 callosum
 decreasedcommunication 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
studies
Strong evidence of genetic component
Predominant theory: Catecholamine
neurotransmitter dysfunction or imbalance
 decreased dopamine and/or norepinephrine
uptake in brain
 theory supported by positive response to
stimulant treatment
Recent study indicates possible lack of serotonin
as a factor in mice
 Dopamine in the Brain

Scientific American
Http//www.sciam.com/1998/0998issue/0998barkely.html#link1
 Genetic Linkages to ADHD
Twin studies by Stevenson, Levy et al, and
Sherman et al indicate an average heritability
factor of .80
Biederman et al reported a 57% risk to offspring if
one parent has ADHD.
Dopamine genes
 DA type 2 gene
 DA 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
 Treatment
Counseling of individual and family
Stimulants
Tricyclic antidepressants
Bupropion
Clonidine
 Stimulants
Exact 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
and pemoline
 Methylphenidate
Is a piperidine Taken orally, 2-3 times
derivative commonly a day as needed
known as Ritalin® Behavioral effects start
Is believed to act as within 1/2 hour to hour
dopamine agonist in after ingestion, peaking
synaptic cleft at 1 and 3 hours
Stimulates frontal- Also comes in
striatal regions Sustained-Release
Dosage (5-20 mg) must form, whose effects last
be adjusted to each approximately twice as
patient long.
 Effects of MPH
Elevates mood
Raises arousal of CNS and cerebral blood
flow
Increases productivity
Improves social interactions
Increases heart rate and blood pressure
Has little or no abuse potential
 Side Effects
 Common:  Mild:
 decreased appetite  anxiety/
 insomnia depression
 behavioral  irritability
rebound  Rare:
 head and stomach  tics (Tourette’s
aches Syndrome)
 overfocussing
 Also thought to cause  liver problems or
temporary height and rash (Pemoline
weight suppression only)
 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
 References
Barkley, R. Attention-Deficit Hyperactivity Disorder, 2nd Ed. New York: Guilford Press. 1998. 628
pp.

Shaywitz, B. and Shaywitz, S. Attention Deficit Disorder Comes of Age: Toward the 21st Century.
Austin, TX: Hammill Foundation. 1992. 366 pp.

Rie, H.E. and Rie, E.D., Eds. Handbook of Minimal Brain Dysfunctions: A Critical View. New
York: John Wiley & Sons. 1980. 744 pp.

Faigel, H. Attention Deficit Disorder: A Review. J. of Adolesc. Health, Mar 1995 Vol. 16: 174-84.

Cantwell, D.P. Attention Deficit Disorder: A Review of the Past Ten Years. J. of the Am. Acad. Of
Child Adolesc. Psychiatry. 1996, Vol 35: 978-87.

Seideman, L., Biederman, J., and Faraone, S.V. A Pilot Study of Neuropsychological Function in
Girls with ADHD. J. of Am. Acad. of Child Adolesc. Psychiatry, 1997. Vol. 36: 366-73.

Seideman, L., Biederman, J., and Faraone, S.V. A Pilot Study of Neuropsychological Function in
Girls with ADHD. J. of Am. Acad. of Child Adolesc. Psychiatry, 1997. Vol. 36: 366-73.
 References
Levy, F., Hay D.A., McStephen, M., Wood, C., and Waldman, I. Attention-Deficit Hyperactivity
Disorder: A Category or Continuum? Genetic Analysis of a Large Scale Twin Study. J. of Am.
Acad. Of Child Adolesc. Psychiatry, 1997, Vol 36: 737-44.

Sherman, D.K., Iacono, W.G., McGue, M.K. Attention-Deficit Hyperactivity Disorder Dimensions:
A Twin Study of Inattention and Impulsivity-Hyperactivity. J. of Am. Acad. Of Child Adolesc.
Psychiatry, 1997, Vol 36: 737-44.

Scientific American Online: http://www.sciam.com/1998/0998issue/0998barkley.html#link1

Ritalin Action on Hyperactivity Explained By New Theory

http://pharmacology.tqn.com/library/99news/bl9n0155d.htm

Approaching a Scientific Understanding of what Happens in the Brain in AD/HD

http://www.chadd.org/attnv4n1p30.htm

Marx, J. How Stimulant drugs May Clam Hyperactivity. Science, 1999, Vol. 283: 306-08.
http://www.sciencemag.org/cgi/content/full/283/5400/306?maxtoshow=&HITS=10&hits=10&RES
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