From: Ben Houston (ben_houston@hotmail.com)
Date: Thu Jun 06 2002 - 21:00:49 MDT
Hi all,
During the weekend IRC session the topic turned to ADHD. Unfortunately I
though that since I have spent a lot of time studying topics related to ADHD
-- the dopaminergic system and its relationship to working memory,
intelligence and drug addiction --that I could discuss ADHD in general with
some authority. I was mistaken and my knowledge of ADHD before and during
the IRC session was very inadequate.
In order to make up for my mistake I have interpreted and transcribed
portions of an authoratative ADHD chapter from my neuropharmacology
textbook: Charney, D.S. et al. 1999. Neurobiology of Mental Illness.
Oxford Press.
If there are any specific questions in regards to this overview I would be
happy to answer them. This time I'll make an effort to base my answers in
established research rather than just resorting to personal pet hypotheses
or my favorite subsystem interaction for this month. ;-)
Kind Regards,
Ben Houston
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ATTENTION DEFICIT / HYPERACTIVITY DISORDER *
* Interpreted and transcribed from: Charney, D.S. et al. 1999. Neurobiology
of Mental Illness. Oxford Press.
Attention deficit disorder (ADHD) is an early onset, clinically heterogenous
disorder of inattention, hyperactivity and impulsivity.
Diagnostic History
Its recognition from a clinical perspective dates at least as far back as
the 1930s. The modern definition of ADHD could be seen in the ancient
clinical definitions of 'minimal brain damage', 'minimal brain dysfunction',
and 'hyperactive child syndrome.' It first entered the standard DSM in 1968
under the heading of 'hyperkinetic reaction of childhood.' The modern
definition of ADHD in DSM-IV lists 3 subtypes: (1) predominantly inattentive
type, predominantly hyperactive-impulsive type, and combined type. The
diagnostic criteria in DSM-IV require clinically significant impairment in
social, academic or occupational functioning.
Childhood, Teenage and Adulthood
Children with ADHD are easily recognized. Their inattention leads to
daydreaming, distractability and difficulties with sustained attention
tasks. Their impulsivity makes them accident prone, creates problems with
peers, and disruptive in classroom settings.
In their teenage years, symptoms of hyperactivity and impulsivity will
deminish, but in the majority of casese the symptoms and impairments of ADHD
will persist. The ADHD teen is at high risk for low selfesteem, poor peer
relationships, conflict with parents, delinquency, smoking and substance
abuse.
Although there is controversy surrounding the question of adult ADHD in the
popular media, longitudinal studies have shown that as much as two thirds of
ADHD children will have impairing ADHD symptoms in adulthood.
Genetic Components
Based on family studies, twin studies, adoption studies, and segregation
analysis studies it seems that there is a large genetic component to ADHD.
The influence of genetics in the development of ADHD varies from between 0.6
and 0.8 in studies. The data suggests that there is no one ADHD gene but
that ADHD results from the interaction of several genes.
Biological relatives of individuals diagnosed with ADHD have shown
consistently poorer than normal scores on standardized tests of attention
than do adopted relatives. (Alberts-Corush et al., 1986)
Biological Adversity
As a result of many claims in the popular media that ADHD results from
specific foods or diets a series of systematic scientific studies have been
conducted on this topic. These studies concluded both that that food
additivies do not cause ADHD and that 'the Feingold diet' was not effective
in treating ADHD (Conners, 1980).
Toxins though have been implicated in the etiology of ADHD. Lead
containmination can lead to distractiability, hyperactivity, restlessness
and lower intellectual functioning. But it does not seem to be a factor in
most ADHD cases and many children exposed to lead do not develop ADHD.
(Needleman, 1982)
Literature concerning pregnancy and delivery complications in assocation
with ADHD has not be conclusive. Some evidence suggests that toxemia,
eclampsia, poor maternal health, maternal age, fetal postmaturity, duration
of labor, fetal distress, low birthweight, and antepartum hemorrhage can
dispose children to ADHD. (Sprich-Buckminster et al. 1993)
Smoking during pregnancy can can damage to the fetus's brain at critical
times in the developmental process. Animal studies have linked chronic
fetal nicotine exposure to hyperactive offspring. (Johns et al., 1992; Van
De Kamp and Collins, 1994)
Neurobiology
At least as early at 1971 (Satterfield and Dawson, 1971) it was proposed
that ADHD results from frontolimbic dysfunction. They suggested that weak
frontal cortical inhibitory control over limbic functions might lead to
ADHD. The success of stimulant medications implicated the dopamine pathway
and lead to more support for the frontolimbic dysfunction hypothesis. (Camp
and Winsberg, 1984) Further support was found in studies that compared
symptomology between adults with frontal lobe damage and ADHD children.
ADHD children perform poorly on standardized tests that require: (1)
organization of cognitive information, (1) inhition of motor responses, (3)
planning, (4) complex problem solving, and (5) the learning and recall of
verbal material. Deficits were found to remain consistent into adulthood.
Orbital frontal (ofPFC) lesions predict social disinhibition and
implusivity. Dorsolateral (dlPFC) lesions affect organizational abilities,
planning, working memory and attention. Thus observed deficits in ADHD from
standardized tests and from observation in social situations implicate both
orbitofrontal and dorsolateral prefrontal cortex dysfunction. The mesial
prefrontal region, where lesions predict dysfluency and slowing of
spontaneous behavior, is not implicated in ADHD.
Because of the limitations of modern neuropsychological inference it is not
clear whether the dysfunction of the prefrontal cortex is due to
abnormalities in the prefrontal cortex itself or due to adnormalities in the
related subcortical circuitry.
Various brain regions are involved in the circuitry underlying the
prefrontal cortex. The cingulate cortex is important in the motivational
aspects of attention and in response selection and inhibition. The right
prefrontal and parietal cortex are activated in sustained and directed
attention across sensory modalities. The inferior parietal cortex and
superior temporal sulcus are polymodal sensory convergence areas that
provide a representation of extrapersonal space which is important in
focusing and selecting target simuli. The reticular activiting system
regulates attentional tone. The regicular thamaic nuclei filter sensory
interference. Working memory deficits implicate various regions including
the anterior hippocampus, ventral anterior and dorsolateral thalamus,
anterior cingulate, parietal cortex and the dorsolateral prefrontal cortex.
CT and MRI studies of ADHD children have found sulci widening and cerebellar
atrophy -- this supports the hypothesis that ADHD is a subcortical syndrome.
Regional cerebral blood flow (rCBF) studies have noted hypoperfusion in
the frontal cortex and hyperperfusion in the pareital cortex. Glucose
metabolism PET studies have found lower glucose metabolism in various brain
regions associated with the attentional networks.
Because of the efficacy of stimulant treatment studies have tried to find
support for a catecholamine hypothesis of ADHD. Such studies that looked at
catecholamine metabolites have found conflicting results -- thus suggesting
that no one single catecholamine neurotransmitter system can account for the
available data.
Pharmacotherapy Treatment of ADHD
The drugs that effectively treat ADHD are known to modulate catecholamine
pathways. These include both methylphenidate, pemoline and
dextroamphetamine. Many studies have documented stimulant-induced
improvements in measures of vigilance, cognitive impulsivity, reaction time,
short-term memory, learning of verbal and nonverbal material in children
with ADHD. Effects seem to be dose dependent.
In addition to stimulants, tricyclic antidepressants (TCAs) also play a role
-- specifically imipramine. Although most studies of TCAs in relation to
ADHD have been brief (< 2 years) they suggest that TCAs produce moderate to
strong treatment effects. Neuropsychological tests, in contrast to positive
clinician ratings, shows varied response. In comparison to stimulants 3
studies have shown TCAs to be inferior, 5 studies showed TCAs were equal in
effectiveness and 2 studies shows that TCAs were superior to stimulants.
Nicotine has shown some effectiveness in attenuating ADHD symptoms. This
positive effect of nicotine may explain why individuals diagnosed with ADHD
have a higher than average probability of smoking.
Drugs that have not been effective in the treatment of ADHD include:
lithium, meprobamate, hydroxyzine, fenfluramine, dopamine agonists, amino
acid precursors and caffieine.
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