Lecture 19; November 19, 2013

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ADHD

Book recommendation

In the Realm of the Hungry Ghosts Gabor Mat

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Die Geschichte vom Zappel-Philipp: An early tale of ADHD?!

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Die Geschichte vom Zappel-Philipp: An early tale of ADHD?!

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Introduction to ADHD
Attention-Deficit/Hyperactivity Disorder (ADHD) is
classified as a developmental disorder by the DSM5.

Disorders that initially present in children tend to be labeled

as developmental disorders.

The essential feature of ADHD is a persistent pattern of

inattention and/or hyperactivity-impulsivity.
Importantly, these factors must be shown to impact
development in a clinically significant manner.
Hyperactivity refers to excessive motor activity at
inappropriate times.

This could include running around, fidgeting, tapping, or

talkativeness.

Impulsivity refers to hasty actions that occur in the

moment without any kind of forethought.

Clinically relevant forms of impulsivity typically involve

possibly harmful behavior (i.e. running into traffic).

ADHD begins in childhood, and the DSM5 requires that

symptoms be present before age 12.
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Introduction to ADHD
Children inevitably have occasional bouts of inattentiveness or
hyperactivity those are part of growing up. A key feature of the ADHD
diagnostic is that manifestations of the disorder must appear in multiple
settings.

This means that ADHD symptoms are not just limited to one place (school, for
example), but appear no matter where the child is.

Context matters. Signs of the disorder may be minimal or absent when the
individual is under close supervision, receiving frequent rewards for good
behavior, in a novel setting, or doing something interesting.
This can make the disorder challenging to diagnose, as the doctors office often
meets all of the above criteria.

The issues associated with ADHD tend to create other problems in the
childs life.

Academic performance tends to suffer. Social rejection is common as well.

ADHD is not considered an intellectual disorder per se. Nevertheless, mild

delays in language, motor and social development are common in children
with ADHD.

This could be a consequence of simply not paying sufficient attention to things.

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Prevalence of ADHD
ADHD can be diagnosed in
approximately 2-5% of children in
the US, 80% of which are boys.

Adult ADHD may have a prevalence

as high as 2.5%. Longitudinal
studies of ADHD show that
symptoms gradually reduce across
the lifespan.
Impulsivity and hyperactivity tend to
drop off more than attention. Many
adults continue to struggle with
attention their entire lives.

ADHD prevalence appears to vary

worldwide, though not by as much
as is often claimed.

North America, when considered as

a whole, has higher rates of ADHD
than most other places (South
America and Africa being
exceptions).

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Worldwide prevalence estimated by meta-analysis of 102

ADHD studies (Polanczyk 2007).

Prevalence of ADHD
Several challenges exist in interpreting ADHD prevalence
data.
Diagnostic criteria can vary between studies. In the
meta-analysis given in the last slide, this was controlled
for statistically.

Studies using the DSM-III or the ICD-10 (a manual of

disease classification published by the World Health
Organization) found lower rates of ADHD than studies that
used the DSM-IV.

DSM diagnostic criteria has changed over time.

ADD was first defined in the DSM-III with three domains:

Inattention, Impulsivity, and Hyperactivity. Children required
several symptoms in each domain to receive a diagnosis.
In the DSM-IV continued with this model, but allowed for
diagnosis of either symptoms of inattention or hyperactive
symptoms. These seem to be less strict diagnostic criteria.
The DSM5 retains similar criteria to the DSM-IV.

These issues can make it dicult to tell whether ADHD

rates are actually increasing, or if its simply a matter of
diagnostic criteria changing.
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Prevalence of ADHD
Even with the same ocial diagnostic criteria, the
diagnosis of ADHD is dicult to separate from the
cultural context.
The current DSM5 diagnostic criteria still seem to be
based largely on elementary school aged North
American boys.
If ADHD occurs everywhere in the world, it would still
only be diagnosable in certain cultural contexts.

If ADHD prevalence is roughly the same

worldwide, would it be noticed in huntergatherer children?

Hyperactivity and inattentiveness would not be as

much of a concern in times and places where children
do not go to school.
On the other hand, in areas where academic
achievement is prized above all else, even minor levels
of inattentiveness and hyperactivity would seem
pathological.

The rich interaction between cultural factors and

ADHD is not unique.
As we have seen, disorders such as anorexia nervosa
are also highly dependent on cultural context.
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Or would it only be seen when children

are subjected to extremely high
academic standards from an early age?

Comorbidity of ADHD

Only about 1/3 of children are diagnosed with ADHD alone. The
majority are diagnosed with at least one other DSM disorder.
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Genetics of ADHD
ADHD is elevated in first-degree biological
relatives of individuals with ADHD.
First-degree biological relatives are relatives that
share 50% of their genetic material. Your siblings
are your first-degree relatives, as are your parents.

The etiology of ADHD has been suggested to

be up to 80% genetic. This makes it one of the
most heritable disorders.
In spite of the strong evidence for a genetic link,
research has not yet uncovered much in the way
of specific genes that might be to blame.
Weak associations have been found with genes for
the dopamine reuptake transporter and the D4
dopamine receptor.
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Environmental/developmental risk factors

There is evidence for gene-environment interactions in
ADHD.
Children with a specific mutation in the dopamine
reuptake transporter (DAT1) are more likely to exhibit
symptoms of ADHD if their mothers smoked during
pregnancy.
Perinatal hypoxia a temporary shortage of oxygen
around the time of birth has also been linked to the
development of ADHD.
There is no convincing evidence that ADHD in the general
population can be caused by exposure to food coloring or
preservatives.

Children who are known to be sensitive to these things do

show some hyperactivity when they are exposed, but they are
not reflective of all ADHD cases.

There is also no evidence that ADHD is caused by, or
exacerbated by sugar.
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The Stanford marshmallow experiment

In the late 1960s, psychologist Walter Mischel
came up with an experiment to test childrens ability
to delay gratification.
In this experiment, children (ages 4-6) were brought
into the lab and oered a treat of some kind, usually
a marshmallow.
They were told that they could eat the marshmallow
right away, or they could wait 15 minutes and get
two marshmallows instead.
The experimenter would then leave the room, and
observe the child through a two-way mirror.
Children would struggle to resist their urge to eat the
marshmallow. This level of self-control is quite difficult
for a young child.
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The Stanford marshmallow experiment

When re-examined years later, it turned out that the childs
ability to delay gratification in this simple test was very
predictive of their future success in life.
Academic success, motivation, self-control, planning,
executive function, and SAT scores were all correlated with
performance on the marshmallow test.

Grownup children from the study, 40 years after the fact,

were subjected a to a go/no-go experiment that tests
response inhibition, a form of impulse control while in an
fMRI brain scanner.

The authors of this study found that performance on this task

was still worse in those who had given in to marshmallow
temptation as youngsters.
They also found that people who had been tempted showed
increased ventral striatum activity and decreased prefrontal
cortex activity relative to those who had resisted temptation.

The results of these studies seem to suggest that the ability

to delay gratification is a skill that persists over the
lifetime, and has a neurobiological basis.
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Behavioral markers of ADHD

Children with ADHD will usually opt for immediate
reward in psychological studies (such as the
marshmallow study).
This seems to happen regardless of previous
experience in the experiment.

Rewards apparently have less of an influence over

the behavior of children with ADHD.
Childrens performance in various cognitive tasks
(tests of reaction time, accuracy, etc.,) improves
when a reward is offered. This is not the case in
children with ADHD their performance remains low
irrespective of reward.

Children with ADHD have impaired performance in

go/no-go tasks.
Interestingly, relatives of children with ADHD also
show impaired performance on these tasks, even if
they dont have the disorder themselves. This
suggests a possible endophenotype.

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Behavioral markers of ADHD

There is some evidence showing that
children with ADHD take more risks in
gambling experiments.

So it seems that children with ADHD,

despite their best intentions, make poor
choices with respect to rewarding
situations.
These deficits point to issues with either
executive function (frontal lobe) or reward
function (mesocorticolimbic dopamine
system), or perhaps both at the same
time.
The Dual Pathway Model is a theory about
ADHD suggesting dysfunctions in both
systems are to blame.

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Neuroimaging findings in ADHD

Numerous studies have shown evidence
for structural and functional brain
abnormalities in children with ADHD.
Children with ADHD often have reduced
volume of certain parts of the prefrontal
cortex (PFC), striatum, cerebellum, and
corpus callosum.
Problems with the PFC and striatum are
perhaps not surprising, given the deficits
in executive function and reward
processing seen in ADHD.
Findings in the cerebellum and corpus
callosum are somewhat more difficult to
explain
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Treatment of ADHD
Despite the complexity of the ADHD diagnosis, the
ecacy of the available pharmacological treatment
options is actually quite good.

Psychostimulant drugs are effective in 70-90% of cases.

The most common pharmacological treatments for

ADHD are drugs of the psychostimulant variety.
These have been in regular use since at least the
1970s.

Psychostimulants are drugs that stimulate the brain, and

generally increase the activity of the CNS.
Caffeine is an example of a legal psychostimulant,
methamphetamine and cocaine are two examples of
illegal psychostimulants.

Popular drugs include methylphenidate (Ritalin),

amphetamine (Adderall), and d-amphetamine
(Dexedrine).
These drugs are given at low doses, in long-acting, slowrelease formats that limit the rush that characterizes
their illegal counterparts.
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Worldwide use of methylphenidate

Almost without exception, the rate of methylphenidate (Ritalin) use is increasing

worldwide.
Its not likely that the rate of ADHD has increased appreciably over these years.
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Non-drug treatments for ADHD

Numerous non-drug treatments for ADHD have been proposed.

Unfortunately, they do not seem to be very eective in controlled studies.
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Ethics of ADHD treatment

Because ADHD is mostly a disorder of childhood, its treatment requires special
consideration.
It is often suggested that children are overmedicated, or that medication is used as
a substitute for eective parenting/schooling.
Children are not small adults, so studies of drug eects on adult brains cannot be
safely generalized to children.
Emerging data from animal studies of chronic psychostimulant treatment suggest
that long-term side eects may exist.
Chronic methylphenidate treatment in young rats reduces the rewarding power of
cocaine in adulthood.
Chronic amphetamine treatment reduces dopamine terminals in the striatum of
monkeys.

ADHD symptoms do tend to improve on their own as the child ages. Should we
just leave ADHD alone and let it resolve itself?
Academic and social success during childhood strongly influences the rest of the
individuals life. The possible risks of medication may be a fair tradeoff for a lifetimes
worth of positive outcomes?

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Is ADHD real?
The existence of ADHD is fairly uncontroversial among neuroscientists
and psychiatrists, but its existence is disputed by other academics and
the popular press.
Arguments used by those who deny the existence of ADHD are from a
common stock of arguments used by deniers of everything else.

Perhaps ADHD is simply the medicalization of youthful

rambunctiousness. Maybe its an eort to sell more drugs to kids? It
could even a childs way of communicating dissatisfaction with their
current home/school environment
The fact that drugs are eective in treating ADHD does not necessarily
point to a real underlying condition these drugs can help anybody pay
attention.
The fact that modern diagnostic criteria for ADHD can produce reliable
results, combined with the observation of neurobiological and behavioral
correlates of the disorder suggest that it is real.
Still, a nuanced view of mental illness is valuable

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A good way to think about mental illness

Every human trait can be measured along a spectrum. The
majority of people fall somewhere in the middle of the range.
A minority of people may be on either the high or low
extremes.
Based on their relative success in things that seem to
matter, we establish cuto lines at the high and low ends
of the spectrum. Those falling outside the cuto lines
may be considered ill, or perhaps gifted, whatever the
case may be.

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A good way to think about mental illness

Every aspect of our psychological function is related to the
brain in some fashion. If you think about it, it has to be this way.
What other part of the body could they possibly relate to?
This is why scientists speak of the
neural correlates of behavior.
Dierences in brain function correlate
with dierences in behavioral and
psychological function.

This approach tells us a great deal about how the

brain works, and how psychological issues can be
treated using neuroscience. But does it make
mental illnesses any more real? Or does it simply
move the problem inward?
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So is ADHD real?
If the previous two slides were eective, then you
should understand that any aspect of human
variation, be it physical or psychological, could be
classified as a disorder if it is suciently dierent
from average.
But cuto points are fluid they change over time,
across cultures, and between editions of the DSM.
They also change as we understand more and more
about the brain.

So if we decide to question the ontological status of

ADHD, we might justifiably ask the same questions
about any other mental illness even one as severe
as schizophrenia
(and yes, people do occasionally argue that
schizophrenia doesnt exist)

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