ADHD
Attention-deficit/hyperactivity disorder
(ADHD) is a neuropsychiatric condition
affecting preschoolers, children,
adolescents, and adults around the
world, characterized by a pattern of
diminished sustained attention, and
increased impulsivity or hyperactivity
The prefrontal cortex of the brain has
been implicated because of its high
utilization of dopamine and its
reciprocal connections with other brain
regions involved in attention, inhibition,
decision-making, response inhibition,
working memory, and vigilance.
Children, adolescents, and adults with
ADHD often have significant
impairment in academic functioning as
well as in social and interpersonal
situations
ADHD is frequently associated with
comorbid disorders including learning
disorders, anxiety disorders, mood
disorders, and disruptive behavior
disorders.
Epidemiology
ADHD affects up to 5 to 8 percent of
school-aged children, with 60 to 85
percent of those diagnosed as children
continuing to meet criteria for the
disorder in adolescence, and up to 60
percent continuing to be symptomatic
into adulthood.
Rates of ADHD have been reported to
be 7 to 8 percent in prepubertal
elementary school children.
Epidemiologic studies suggest that
ADHD occurs in about 5 percent of
youth including children and
adolescents, and about 2.5 percent of
adults
Rate of ADHD in parents and siblings of
children with ADHD is 2 to 8 times
greater than in the general population
ADHD is more prevalent in boys than in
girls, with the ratio ranging from 2: 1 to
as high as 9: 1
Symptoms of ADHD are often present
by age 3 years, but unless they are very
severe, the diagnosis is frequently not
made until the child is in kindergarten,
or elementary school, when teacher
information is available comparing the
index child peers of the same age.
Etiology
Largely genetic, with a heritability of
approximately 75 percent.
ADHD symptoms are the product of
complex interactions of
neuroanatomical and neurochemical
systems evidenced by data from twin
and adoption family genetic studies,
dopamine transport gene studies,
neuroimaging studies, and
neurotransmitter data.
Most children with ADHD have no
evidence of gross structural damage in
the central nervous system (CNS).
In some cases, contributory factors for
ADHD may include prenatal toxic
exposures, prematurity, and prenatal
mechanical insult to the fetal nervous
system
GENETICS
o Increased concordance in
monozygotic compared to
dizygotic twins, as well as a
marked increased risk of 2 to 8
times for siblings as well as
parents of an ADHD child,
compared to the general
population
o Up to 70 percent of children
with ADHD meet criteria for a
comorbid psychiatric disorder,
including learning disorders,
anxiety disorders, mood
disorder conduct disorders, and
substance use disorders
o Several hypotheses of the mode
of transmission of ADHD have
been proposed, including a sex-
linked hypothesis, which would
explain the significantly
 increased rates of ADHD in
males.
o Cook and colleagues have
found an association of the
dopamine transporter gene
(DAT 1) with ADHD, although
data from other research
groups have not confirmed that
result.
o Family studies and population-
based studies have found an
association between the
dopamine 4 receptor seven-
repeat allele gene (DRD4) gene
and ADHD.
NEUROCHEMICAL FACTORS
o Dopamine is a major focus of
clinical investigation, and the
prefrontal cortex has been
implicated based on its role in
attention and regulation of
impulse control
o Animal studies have shown that
other brain regions such as
locus ceruleus, which consists
predominantly of noradrenergic
neurons, also play a major role
in attention.
o Hypotheses regarding the
neurochemistry of ADHD have
arisen from the predictable
effect of medications.
o Simulants, known to be the
most effective medications in
the treatment of ADHD, affect
both dopamine and
norepinephrine, leading to
neurotransmitter hypotheses
that may include dysfunction in
both the adrenergic and
dopaminergic systems.
o Stimulants increase
catecholamine concentrations
by promoting their release and
blocking their uptake
NEUROPHYSIOLOGICAL FACTORS
o EEG studies in ADHD children
and adolescents over the last
several decades have found
evidence of increased theta
activity, especially in the frontal
regions.
o Clarke and colleagues, studying
EEG findings in children and
adolescents over the last two
decades found that those ADHD
children with combined type of
ADHD were the ones who
showed significantly elevated
beta activity on EEG, and
further studies indicate that
these youth also tend to show
increased mood lability and
temper tantrums
NEUROANATOMICAL ASPECTS
o Researchers have hypothesized
networks within the brain for
promoting components of
attention including focusing,
sustaining attention, and
shifting attention.
o Neuroanatomical correlations
for the superior and temporal
cortices with focusing
attention; external parietal and
corpus striatal regions with
motor executive functions; the
hippocampus with encoding of
memory traces; and the
prefrontal cortex with shifting
from one stimulus to another.
o Further hypotheses suggest
that the brainstem, which
contains the reticular thalamic
nuclei function, is involved in
sustained attention.
o MRI, PET, and SPECT suggests
that populations of children
with ADHD show evidence of
both decreased volume and
decreased activity in prefrontal
regions, anterior cingulated,
globus pallidus, caudate,
thalamus, and cerebellum
o PET scans have also shown that
female adolescents with ADHD
 have globally lower glucose
metabolism than both control
female and male adolescents
without ADHD.
DEVELOPMENTAL FACTORS
o Higher rates of ADHD are
present in children who were
born prematurely and whose
mothers were observed to have
maternal infection during
pregnancy
o Perinatal insult to the brain
during early infancy caused by
infection, inflammation, and
trauma may, in some cases, be
contributing factors in the
emergence of ADHD symptoms.
o Children with ADHD have been
observed to exhibit nonfocal
(soft) neurological signs at
higher rates than those in the
general population
PSYCHOSOCIAL FACTORS
o Severe chronic abuse,
maltreatment, and neglect are
associated with certain
behavioral symptoms that
overlap with ADHD including
poor attention and poor
impulse control.
o Predisposing factors may
include the child's
temperament and genetic-
familial factors.
Clinical Features
ADHD can have its onset in infancy,
although it is rarely recognized until a
child is at least toddler age.
More commonly, infants with ADHD are
active in the crib, sleep little, and cry a
great deal.
In school, children with ADHD may
attack a test rapidly, but may answer
only the first two questions. They may
be unable to wait to be called on in
school and may respond before
everyone else. At home, they cannot be
put off for even a minute.
Impulsiveness and an inability to delay
gratification are characteristic. Children
with ADHD are often susceptible to
accidents.
The most cited characteristics of
children with ADHD, in order of
frequency, are hyperactivity, attention
deficit (short attention span,
distractibility, perseveration, failure to
finish tasks, inattention, poor
concentration), impulsivity (action
before thought, abrupt shifts in activity,
lack of organization, jumping up in
class), memory and thinking deficits,
specific learning disabilities, and
speech and hearing deficits.
Associated features often include
perceptual motor impairment,
emotional lability, and developmental
coordination disorder.
Course and Prognosis
Symptoms have been shown to persist
into adolescence in 60 to 85 percent of
cases, and into adult life in
approximately 60 percent of cases.
The remaining 40 percent of cases may
remit at puberty, or in early adulthood.
In some cases, the hyperactivity may
disappear, but the decreased attention
span and impulse-control problems
persist.
Overactivity is usually the first
symptom to remit, and distractibility is
the last.
ADHD does not usually remit during
middle childhood.
When remission occurs, it is usually
between the ages of 12 and 20.
Most patients with the disorder,
however, undergo partial remission and
are vulnerable to antisocial behavior,
substance use disorders, and mood
disorders. Learning problems often
continue throughout life.
In about 60 percent of cases, some
symptoms persist into adulthood. Those
 who persist with the disorder may show
diminished hyperactivity but remain
impulsive and accident-prone.
Children with ADHD whose symptoms
persist into adolescence are at higher
risk for developing conduct disorder.
Children with both ADHD and conduct
disorder are also at risk for developing
substance use disorders
Optimal outcomes may be promoted by
ameliorating children's social
functioning, diminishing aggression, and
improving family situations as early as
possible
Treatment
PHARMACOTHERAPY
Considered the first line of treatment
for ADHD
CNS stimulants are the first choice of
agents in that they have been shown to
have the greatest efficacy with
generally mild tolerable side effects.
Stimulants are contraindicated in
children, adolescents, and adults with
known cardiac risks and abnormalities.
Nonstimulant medications approved by
the FDA in the treatment of ADHD
include atomoxetine (Strattera), a
norepinephrine uptake inhibitor.
-agonists (clonidine, guanfacine) have
also been found to be effective in
treating ADHD
STIMULANT MEDICATIONS
o Methylphenidate and
amphetamine preparations are
dopamine agonists; however,
the precise mechanism of the
stimulant's central action
remains unknown
o Methylphenidate preparations
have been shown to be highly
effective in up to three fourths
of children with ADHD, with
relatively few adverse effects.
o Concerta, the 10- to 12-hour
extended release OROS
(osmotic controlled-release
extended delivery system) form
of methylphenidate, is
administered once daily in the
morning and is effective during
school hours as well as after
school during the afternoon
and early evening
o Methylphenidate products have
been shown to improve ADHD
children's scores on tasks of
vigilance, such as on math
calculation tests, the
continuous performance task,
and paired associations.
o Adverse effects: headaches,
stomachaches, nausea,
insomnia, rebound effect
(become mildly irritable and
appear to be slightly
hyperactive for a brief period
when the medication wears
off).
o Another common concern
about use of methylphenidate
preparations over long periods
is potential growth suppression.
NONSTIMULANT MEDICATIONS
o Atomoxetine HCl (Strattera) is a
norepinephrine uptake inhibitor
approved by the FDA for the
treatment of ADHD in children
age 6 years and older. The
mechanism of action is not well
understood, but it is believed to
involve selective inhibition of
presynaptic norepinephrine
transporter.
o Unlike the stimulants, Strattera
carries with it a black box
warning for potential increases
in suicidal thoughts or
behaviors and requires children
with ADHD to be monitored for
these symptoms, similarly to
children who are administered
antidepressants.
 o
It has been shown to be
effective for inattention as well
as impulsivity in children and in
adults with ADHD.
o Most common side effects
include diminished appetite,
abdominal discomfort,
dizziness, and irritability.
TREATMENT OF CNS STIMULANTS S/E
o CNS stimulants are generally
well tolerated, and current
consensus is that once a day
dosing is preferable for
convenience and to minimize
rebound side effects.
o Long-term tolerability mild
side effects: decreased
appetite, insomnia, and
headache
o Management of insomnia:
diphenhydramine (25 to 75
mg), low dose of trazodone (25
to 50 mg), or the addition of an
-adrenergic agent, such as
guanfacine.
PSYCHOSOCIAL INTERVENTION
Psychosocial interventions for children
with ADHD include psychoeducation,
academic organization skills mediation,
parent training, behavior modification
in the classroom and at home, cognitive
behavioral therapy (CBT), and social
skills training
Common goal of therapy is to help
parents of children with ADHD
recognize and promote the notion that,
although the child may not "voluntarily"
exhibit symptoms of ADHD, he or she is
still capable of being responsible for
meeting reasonable expectations.
Parents should also be helped to
recognize that, despite their child's
difficulties, every child faces the normal
tasks of maturation, including
Significant building of self-esteem when
he or she develops a sense of mastery
Parental training is an integral part of
the psychotherapeutic interventions for
ADHD
Conduct Disorders
Enduring set of behaviors in a child or
adolescent that evolves over time,
usually characterized by aggression and
violation of the rights of others.
Youth with conduct disorder often
demonstrate behaviors in the following
four categories:
o physical aggression or threats
of harm to
o people, destruction of their
own property or that of others,
o theft or acts of deceit
o frequent violation of age-
appropriate rules
Associated with many other psychiatric
disorders including ADHD, depression,
and learning disorders.
Associated with certain psychosocial
factors, including childhood
maltreatment, harsh or punitive
parenting, family discord, lack of
appropriate parental supervision, lack
of social competence, and low
socioeconomic level
Symptoms include bullying,
threatening, or intimidating others, and
staying out at night despite parental
prohibition.
DSM-5 specifies that when truancy
from school is a symptom, it begins
before 13 years of age.
The disorder may be diagnosed in a
person older than 18 years only if the
criteria for antisocial personality
disorder are not met.
Children with conduct disorder engage
in severe repeated acts of aggression
that can cause physical harm to
themselves and others and frequently
violate the rights of others.
Children with conduct disorder usually
have behaviors characterized by
aggression to persons or animals,
 destruction of property, deceitfulness
or theft, and multiple violations of
rules, such as truancy from school.
Divided into three subtypes, based on
the age of onset of the disorder:
o Childhood-onset subtype
At least one symptom
has emerged
repeatedly before age 1
0 years
o Adolescent-onset type
No characteristic
persistent symptoms
were seen until after
age 10 years
o Unspecified onset
Age of onset is
unknown
Epidemiology
Ratio of conduct disorder in males
compared to females ranges from 4: 1
to as much as 12: 1
Conduct disorder occurs with greater
frequency in the children of parents
with antisocial personality disorder and
alcohol dependence than in the general
population.
The prevalence of conduct disorder and
antisocial behavior is associated with
socioeconomic factors, as well as
parental psychopathology.
Average age of onset of conduct
disorder is younger in boys than in girls.
Boys most commonly meet the
diagnostic criteria by 10 to 12 years of
age, whereas girls often reach 14 to 16
years of age before the criteria are met.
Etiology
Most important risk factors that predict
conduct disorder include
o Impulsivity
o Physical or sexual abuse or
neglect
o Poor parental supervision and
harsh and punitive parental
discipline
o Low intelligence quotient (IQ)
o Poor school achievement
PARENTERAL FACTORS
o Harsh, punitive parenting
characterized by severe
physical and verbal aggression
is associated with the
development of children's
maladaptive aggressive
behaviors
o Chaotic home conditions are
associated with conduct
disorder and delinquency
o Divorce itself is not necessarily
a risk factor
o Parental psychopathology, child
abuse, and negligence often
contribute to conduct disorder
o Sociopathy, alcohol
dependence, and substance
abuse in the parents are
associated with conduct
disorder in their children.
o Studies indicate that parents of
children with conduct disorder
have high rates of serious
Psychopathology, including
psychotic disorders
o Data shows that children who
exhibit a pattern of aggressive
behavior have frequently been
exposed to physically or
emotionally harsh parenting
GENETIC FACTORS
o Genetic, and/or shared
environmental factors exert
different effects on males and
females in childhood conduct
disorder, but by adulthood, the
gender-specific influences on
antisocial behavior are no
longer apparent.
SOCIOCULTURAL FACTORS
o Youth residing in geographic
areas with greater population
density report increased rates
of aggression and delinquency
 oUnemployed parents, lack of a
supportive social network, and
lack of positive participation in
community activities seem to
predict conduct disorder
o Associated findings that may
influence the development of
conduct disorder in urban areas
are increased exposure to and
prevalence of substance use
o Weekly alcohol use among
adolescents is associated with
increased delinquent and
aggressive behavior.
o Although drug and alcohol use
does not cause conduct
disorder, it increases the risks
associated with it. Drug
intoxication itself can also
aggravate the symptoms.
PYSCHOLOGICAL FACTORS
o Poor emotion regulation among
youth is associated with higher
rates of aggression and conduct
disorder.
NEUROBIOLOGICAL FACTORS
o Studies have reported that
children with conduct disorder
had decreased gray matter in
limbic brain structures, and in
the bilateral anterior insula and
left amygdala compared to
healthy controls
o Decreased gray matter in ADHD
and ADHD comorbid for
oppositional defiant disorder or
conduct disorder compared to
controls in regions including
bilateral temporal and occipital
cortices, and the left amygdala
o Low level of plasma dopamine
-hydroxylase, an enzyme that
converts dopamine to
norepinephrine, leading to a
hypothesis of decreased
noradrenergic functioning in
conduct disorder; high plasma
serotonin levels in blood
o Blood serotonin levels correlate
inversely with levels of 5-HIAA
in the cerebrospinal fluid (CSF)
and that low 5-HIAA levels in
CSF correlate with aggression
and violence.
NEUROLOGIC FACTORS
o Aggressive children had
significantly greater relative
right frontal brain activity at
rest compared with
nonaggressive children.
o Frontal resting brain electrical
activity has been hypothesized
to reflect the ability to regulate
emotion
o Boys tended to show lower
emotional intelligence than girls
and greater aggressive behavior
than girls.
CHILD ABUSE AND MALTREATMENT
o Children chronically exposed to
violence, physical or sexual
abuse, and neglect, particularly
at a young age, are at high risk
for demonstrating aggression.
o Severely abused children and
adolescents tend to be
hypervigilant; in some cases,
they misperceive benign
situations as directly
threatening and respond
defensively with violence.
COMORBID FACTORS
o ADHD and conduct disorder are
often found to coexist, with
ADHD often predating the
development of conduct
disorder, and not infrequently
substance abuse.
o Central nervous system injury,
dysfunction, or damage
predispose a child to impulsivity
and behavioral disturbances,
which sometimes evolve into
conduct disorder
Clinical Features
Aggressive antisocial behavior can take
the form of bullying, physical
aggression, and cruel behavior toward
peers.
Children may be hostile, verbally
abusive, impudent, defiant, and
negativistic toward adults.
Persistent lying, frequent truancy, and
vandalism are common.
In severe cases, destructiveness,
stealing, and physical violence often
occur.
Sexual behavior and regular use of
tobacco, liquor, or illicit psychoactive
substances begin unusually early for
such children and adolescents.
Suicidal thoughts, gestures, and acts are
frequent in children and adolescents
with conduct disorder who are in
conflict with peers, family members, or
the law and are unable to problem
solve their difficulties.
Some children with aggressive
behavioral patterns have impaired
social attachments, as evinced by their
difficulties with peer relationships.
Many children with conduct problems
have poor self-esteem, although they
may project an image of toughness.
They may lack the skills to communicate
in socially acceptable ways and appear
to have little regard for the feelings,
wishes, and welfare of others
Many children and adolescents with
conduct disorder suffer from the
deprivation of having few of their
dependency needs met and may have
had either overly harsh parenting or a
lack of appropriate supervision.
Evaluation of the family situation often
reveals severe marital disharmony,
which initially may center on
disagreements about management of
the child.
Children with conduct disorder are
more likely to be unplanned or
unwanted babies.
The parents of children with conduct
disorder, especially the father, have
higher rates of antisocial personality
disorder or alcohol dependence.
Delinquency, also called juvenile
delinquency, is most often associated
with conduct disorder but can also
result from other psychological or
neurological disorders.
Violent Video Games and Violent Behavior
A review of the literature of the effect
of violent video games on children and
adolescents revealed that violent video
game playing is related to aggressive
affect, physiologic arousal, and
aggressive behaviors.
The degree of exposure to violent
games and the more restriction of
activity would be related to a greater
preoccupation with violent themes
Differential Diagnosis
Disturbances of conduct, including
impulsivity and aggression, may occur
in many childhood psychiatric disorders,
ranging from ADHD, to oppositional
defiant disorder, to disruptive mood
dysregulation disorder mood disorder,
to major depression, to bipolar
disorder, specific learning disorders,
and psychotic disorders.
Conduct disorder VS Oppositional
Defiant Disorder: in conduct disorder,
the basic rights of others are violated,
whereas in oppositional defiant
disorder, hostility and negativism fall
short of seriously violating the rights of
others
Both major depressive disorder and
bipolar disorders must be ruled out, but
the full syndrome of conduct disorder
can occur and be diagnosed during the
onset of a mood disorder.
ADHD and learning disorders are
commonly associated with conduct
disorder. Usually, the symptoms of
 these disorders predate the diagnosis of
conduct disorder.
Substance abuse disorders are also
more common in adolescents with
conduct disorder than in the general
population. Evidence indicates an
association between fighting behaviors
as a child and substance use as an
adolescent.
Course and Prognosis
Although assaultive behavior in
childhood and parental criminality
predict a high risk for incarceration later
in life, the diagnosis of conduct disorder
per se was not correlated with
imprisonment.
Best prognosis is predicted for mild
conduct disorder in the absence of
coexisting psychopathology and the
presence of normal intellectual
functioning.
to discourage covert antisocial
incidents.
PSYCHOPHARMACOLOGIC INTERVENTIONS
Placebo-controlled studies on anti-
psychotics (typical and atypical) showed
efficacy for aggressive behavior.
SSRIs, including fluoxetine (Prozac),
sertraline (Zoloft), paroxetine (Paxil),
and citalopram (Celexa), are used
clinically to target symptoms of
impulsivity, irritability, and mood
lability, which frequently accompany
conduct disorder.
Conduct disorder often coexists with
ADHD, learning disorders, and, over
time, mood disorders and substance-
related disorders; thus, the treatment
of concurrent disorders must also be
addressed

Treatment
PSYCHOSOCIAL INTERVENTIONS
Early sustained preventive interventions
can significantly alter the course and
prognosis of aggressive behavior when
it is administered starting at
kindergarten age.
Meta-analysis of controlled trials of CBT
programs indicates that CBT can result
in significant reductions in conduct-
disordered symptoms in children and
adolescents.
CBT treatment interventions that are
proven to be efficacious include the
following:
o Kazdin's Problem-Solving Skills
Training (PSST)
o Parent Management Training
(PMT)
o Incredible Years (IY)
o Anger Coping Program
School settings can also use behavioral
techniques to promote socially
acceptable behavior toward peers and