Externalizing Behavior Disorders

Jess P. Shatkin, MD, MPH

Director of Education and Training
NYU Child Study Center
New York University School of Medicine
“Anyone can become angry, that is easy…but
to become angry with the right person, at
the right time, for the right purpose, and in
the right way…this is not easy.”

--Aristotle
 Learning Objectives
• Residents will be able to:
1) Identify “normal” from aberrant and disruptive
childhood behavior
2) Distinguish between Oppositional Defiant Disorder
and Conduct Disorder
3) Discuss 11 major risk factors for the development of
Disruptive Behavior Disorders in children and
adolescents and identify 3 protective factors
4) Describe one model of delinquency
5) Select appropriate treatments strategies for children
and adolescents with Oppositional Defiant and
Conduct Disorder
 What Constitutes
Normal Social Behavior?
• “Normal” or “typical” children are often
oppositional & defiant
• “Normal” children have tantrums
• “Normal” children are periodically mean-spirited
(in word, deed, and action)
• “Normal” children lie and cheat, and are
sometimes purposefully annoying
• “Normal” children grow out of it
 Oppositional Defiant Disorder
• Pattern of negativistic, hostile, & defiant
behavior lasting at least 6 months w/4 or more
DSM-IV Criteria:
1) Often loses temper
2) Often argues with adults
3) Often actively defies or refuses to comply w/rules
4) Often deliberately annoys others
5) Often blames others for his/her mistakes or behavior
6) Often touchy or easily annoyed by others
7) Often angry and resentful
8) Often spiteful or vindictive
 Epidemiology
• Rates vary (2 – 16% reported; overall 5%)
• Rate decreases with age
• Diagnostic Stability:
– Greater stability with more severe ODD/CD
– Stability as high or higher for females vs. males
• More common in lower SES
 Natural History
• Gender differences don’t emerge until after 6 y/o
• More prevalent in males prior to puberty; rates
equalize (m:f) after puberty
• Usually evident by 8 y/o
• Symptoms often emerge at home but generalize with
time
• Earlier onset  worse prognosis
• Onset is typically gradual over months or years
• ODD can be relatively benign but sometimes lies on a
continuum with CD (30 – 40% of individuals move
from one stage to the next: ODD  CD  APD)
 Associated Features
• During school years there may be low self-
esteem (or over inflated self-esteem), mood
lability, low frustration tolerance, swearing,
and precocious use of EtOH/drugs
• Common Axis I Comorbidities:
– ADHD, Learning D/O, & Communication D/O
– 50% of kids w/ADHD have ODD or CD
– 70% of kids w/ODD or CD have ADHD
Harry Potter and the Sorcerer’s Stone
• The 1st film (based on the 1st book) in the Potter series,
released in 2001
• A classic “Cinderella” story
• Harry, whose parents were killed during his infancy, is
raised by his terrible aunt and uncle, who dote on their
son, Dudley; Harry is treated as the family slave,
regarded with contempt and suspicion
• An example of poor parental supervision & parent’s fear
of conflict with their child, leading to
oppositional/defiant and manipulative behavior
 Conduct Disorder
• A repetitive/persistent pattern of behavior in
which the basic rights of others or major age-
appropriate societal norms are violated; 3 or
more symptoms w/in the past 12 months (at
least one symptom in the past 6 months):
• DSM-IV Criteria:
1) Aggression to people or animals
2) Destruction of property
3) Deceitfulness or theft
4) Serious violations of rules
 Subtypes of Conduct Disorder
• Two subtypes, based upon age of onset, which differ in
presenting symptoms, developmental course, prognosis, &
gender:
1) Childhood-Onset Type (“unsocialized”)
*at least one criterion before age 10 y/o
*usually male; frequently aggressive
*disturbed peer relations
*often suffered ODD as a child; may have concurrent ADHD
*most likely to have persistent CD and to develop APD
2) Adolescent-Onset Type (“socialized”)
*absence of criteria prior to age 10 y/o
*less likely to display aggressive behaviors
*tend to have normative peer relations
*less likely to suffer persistent CD and to develop APD
*still more males:females, but a lower ratio
 Epidemiology
• Rates vary from 1 – 10%; 6% overall
(males: 6 – 16%; females: 2 – 9%)
• Rate increases with age (vs. ODD)
• Diagnostic stability:
*44 – 88% at 3 – 4 years post initial diagnosis
 Natural History
• ODD is a common precursor; less severe
behaviors tend to emerge first (lying, shop-
lifting, fighting, etc.)
• Onset is rare after 16 y/o
• In some cases the behaviors are adaptive or
protective (e.g., threatening, impoverished, high-
crime neighborhoods) and a diagnosis may not
be appropriate
• In the majority, the disorder remits by adulthood,
but a substantial proportion (30 –40%) go on to
develop Antisocial PD
 Associated Features (1)
• Increased accident rates
• Generally lower (occasionally inflated) self-esteem
• Often associated w/early sexual behavior (STDs &
pregnancy), increased EtOH/drug abuse, and risk-taking
• More commonly attend alternative schools and live in
foster placements
• SI/SA & completion occurs at a higher rate
• “Depressive Conduct D/O” (odds of DBD when
depression present @ OR = 2.9)
• Common Axis I Comorbidities:
– ADHD, LD, Communication D/O, Anxiety D/O, Mood D/O,
SUDS
 Associated Features (2)
• Cruelty to people and weapon use best
predict later diagnosis of CD in children
• Below age 13, cruelty, running away, and
breaking & entering is highly predictive of
later CD
 A Model of Delinquency

Poor parental child Rejection by

monitoring & normal peers
discipline conduct & academic
problems difficulties

Commit-
ment to
deviant
Delinquency peer
groups
 Child Biological Factors Possibly
Contributing to ODD & CD (1)
• Family History (potential links)
– Maternal smoking?
– Parental substance abuse
– Pregnancy and birth problems
• Neuroanatomy
– Decreased glucose metabolism associated w/violence
– (Orbito)frontal damage associated w/aggression
– Impairments in amygdala function may be associated with
deficits in interpretation of social cues, such as facial
expression; and a connection between amygdala and PFC may
aid in suppression of negative emotion
 Child Biological Factors Possibly
Contributing to ODD & CD (2)
• Neurotransmitters
– Low levels of serotonin metabolite (5-HIAA) in CSF has been
linked to current and future aggression
– Blood serotonin is higher in boys w/childhood vs. adolescent
onset CD and positively associated w/violence in adolescence
(these findings may suggest lower turnover of central
serotonin; or perhaps slower utilizers of 5-HT in CNS)
– Low salivary cortisol levels associated w/ODD
– Testosterone has been variably associated with aggression
• Autonomic Nervous System
– Possible general physiological under-arousal (e.g., lower heart
rate at baseline, lower skin conductance); while experimentally
induced frustration leads to a higher HR for ODD/CD kids
 Child Biological Factors Possibly
Contributing to ODD & CD (3)
• Neurotoxins
– Lead (preventable risk factor); high levels of lead in 11
y/o children is associated w/increased aggression and
higher delinquency scores
 Child Functional Factors Possibly
Contributing to ODD & CD (1)
• Temperament
– Difficult temperament (e.g., negative emotionality, intense and
reactive responding, and inflexibility) is predictive of
externalizing behavior
• Attachment
– Research is equivocal
• Intelligence
– Low verbal IQ possibly a precursor (most studies have not
controlled well for ADHD)
– Reading disorders may promote disruptive behavior more in
girls than boys
 Child Functional Factors Possibly
Contributing to ODD & CD (2)
• Impulsivity and Behavioral Inhibition
– Behavioral inhibition (shyness) decreases the risk of later
delinquency (likely related to anxiety, which has been shown to
moderate physical aggression, even in already disruptive boys)
– Socially withdrawn boys, however, have grtr risk of delinquency
• Social Cognition
– Boys w/DBD focus more on concrete/external qualities and are
egocentric in describing peers
– Boys w/DBD & boys w/ADHD have problems encoding social
cues; but boys w/DBD more often select aggressive responses to
problems and feel more confident in their ability to carry out an
aggressive response
– Boys and girls with CD have less empathy; and it’s known that
empathy mediates aggressive behavior
 Child Functional Factors Possibly
Contributing to ODD & CD (3)
• Puberty
– Early physical maturation is associated with increased
problem behaviors in girls, not boys
 Psychosocial Factors Possibly
Contributing to ODD & CD (1)
• Parenting
– Poor parenting is related to disruptive behavior, while favorable
parenting may be protective
– Parental psychopathology may be more predictive of DBD in
children than poor parenting
– Aspects of parenting associated w/disruptive behavior:
• Poor monitoring
• Harsh & inconsistent (punitive) discipline
• Differential treatment between siblings
• Coercive parenting
• Mild physical punishment weakly related; more severe/abusive physical
punishment is strongly related
 Psychosocial Factors Possibly
Contributing to ODD & CD (2)
• Assortative Mating
– Females offenders are more likely to cohabit or marry male
offenders than male offenders are to select female offenders
• Child Abuse
– Harsh/abusive parenting and sexual abuse increase risk of CD
– Some data to suggest that abused children have social
processing deficits, such as hostile attribution biases, encoding
errors, and positive evaluations of aggression
– Regarding sexual abuse, boys are less likely than girls to
respond w/internalizing problems but are equally or more likely
than girls to demonstrate conduct problems
 Psychosocial Factors Possibly
Contributing to ODD & CD (3)
• Peer Effects
– Adolescents spend 1/3 of their time w/peers (vs. 8% w/adults)
– Affiliation w/like peers fixes the behavior and social role of
children w/CD
– Chronically maltreated children are more aggressive and more
commonly rejected by peers
– Aggressive girls may be more rejected by peers than aggressive
boys
• Neighborhood & Socioeconomic Factors
– Disruptive behavior is associated w/poor and disadvantaged
neighborhoods
– Availability of drugs, community disorganization, neighborhood
adults involved in crime, poverty, exposure to violence & racial
prejudice are all predictive of later violence
 Willy Wonka and
the Chocolate Factory
• Based upon the popular novel, Charlie and the Chocolate
Factory, released 1971
• Tells the story of Charlie Bucket, a poor but honest child,
desperate to find a “golden ticket” (release from his
horrible life) into Wonka’s magical factory
• Veruca Salt, one of many demanding, manipulative, and
intolerable children in the movie, is completely in control
of her hapless parents
• The Oompah-Loompah’s infectious melodies punctuate
the story and spell-out the cause of such problems (poor
parental control)
 Summary of Major Risk Factors
• Parental neglect
• History of physical or sexual abuse
• Difficult early temperament
• Harsh parental discipline practices
• Inconsistence in primary caregivers
• Large family
• Association with deviant peer group
• Low verbal intelligence
• Parent history of CD and/or Antisocial PD
• Low SES
• Neighborhood disorganization & violence
 Protective Factors
• The opposite of risk factors?
• 3 Protective Factors for ODD:
1) Good relations with at least one parent
2) Good peer relations
3) Good parental monitoring
 Treatment (1)
• Treatment of comorbidities is key
• Individual (child-focused) treatments are by and
large not useful
• Parent Management Training is a well established
treatment (up to 70% sustained reduction in
symptoms) in RCTs
• Parent Child Interactional Training (PCIT) is
useful for ODD with younger children
 Treatment (2)

• Community Based Treatments:

– Foster care (modest positive change for severely
disruptive children)
– School programs to reduce bullying (mixed results)
– Peer group interventions (mixed results)
 Treatment (3)

• Psychopharmacological Interventions:
– Depressive CD should be treated as depression
• A subset of CD is likely secondary to depression
• The DSM-V may reflect a new diagnosis of Conduct
Disordered Depression
• This “diagnosis” should be treated as depression
 Lithium
• Two randomized controlled trials compared LiC03 with
placebo and found that at therapeutic levels LiC03 was
efficacious and safe for the short-term treatment of
aggressive, inpatient children and adolescents with CD
– Campbell et al, 1995 (n=50); Malone et al, 2000 (n=40)
• A 3rd study of a small sample of inpatient adolescents
found no difference between LiC03 and placebo but the
trial was only two weeks in duration
– Rifkin et al, 1997
• An RCT comparing LiCO3, haldol, and placebo for 61
aggressive inpatient children found haldol & LiC03
efficacious with LiC03 having a favorable SEfx profile
– Campbell et al, 1984
 Potpourri
• Carbamazepine at therapeutic levels was not
significantly better than placebo for the treatment
of a small sample of aggressive hospitalized
children with CD
– Cueva et al, 1996
• Both molindone and thioridazine were efficacious
for the treatment of hospitalized aggressive
children, but molindone was better tolerated
– Greenhill et al, 1985
• Beta-blockers may be useful as adjunctive agents
(suggested by case series and reports)
 Clonidine
• Small RCTs have shown that clonidine might be
useful for aggressive behavior in children with
ADHD and comorbid ODD or CD
– Connor et al, 2000; Hunt et al, 1996
• In a meta-analysis of 11 double-blind,
randomized, controlled studies from 1980 to
1999, clonidine demonstrated a moderate effect
size (0.58) on symptoms of ADHD comorbid
with CD, developmental delay, and tics
– Connor et al, 1999
 Risperidone
• Two identical 6-week, multicenter double-blind, placebo
controlled trials followed identical protocols comprising
163 boys (ages 5 – 12) total with ODD or CD,
subaverage intelligence (IQ 36 – 84), and with or
without ADHD demonstrated a decline in aggression by
an average of 56.4% vs. placebo (21.7%)
– TRAY Studies: Aman et al, 2002; Snyder et al, 2002; LeBlanc
et al, 2005
• Large scale review of pilot, open label, and larger
clinical trials of over 800 children & adolescents with
ODD, CD, and DBD NOS exposed to risperidone at
doses of 0.02 – 0.06 mg/kg/day found target symptom
improvement (compared to placebo and baseline
functioning) w/in 1 – 4 weeks of treatment
– Pandina et al, 2006
 Additional Risperidone Studies
• 10-week DBPC trial of 20 child and adolescent
outpatients with aggression and average intellect found a
significant decrease in aggression at low dose (0.028
mg/kg/day)
– Findling et al, 2000
• 4-week DBPC trial of 13 children with low IQ and severe
behavioral problems found statistically significant
improvements in behavior (average dose 1.2 mg/day)
– Van Bellinghen & De Troch, 2001
• Statistically significant reductions in aggression in 38
adolescents with aggression and subaverage cognitive
abilities (average final dose 2.9 mg/day)
– Buitelaar et al, 2001)
 Risperidone cont’d
One recent study challenged 25 children w/ADHD, 7-12
years, who had persistent aggression with Risperidone
augmentation to their stimulant.

They were treated for 4 weeks, randomized and double-

blinded, to placebo or medication. The primary efficacy
measure was change from baseline in the Children's
Aggression Scale-Parent (CAS-P) and -Teacher (CAS-T)
total scores.

The mean risperidone dose at endpoint was 1.08 mg/day.

For the CAS-P total score, a significant difference was
found with 100% of risperidone subjects improving by more
than 30% from baseline to endpoint, whereas only 77% of
the placebo group reported a similar response. No
differences were found on the CAS-T total score. Rates of
adverse events did not differ significantly between groups.
 Quetiapine

• Eight week, open label, outpatient trial of 17

patients aged 6 – 12 years with CD showed
significant reductions in aggression by study end
(average dose 4.4 mg/kg/day)
– Findling et al, 2006
 Quetiapine (2)
• 7 week RDBPC trial of Quetiapine vs placebo in adolescents with
conduct disorder
• N = 19 (9 on quetiapine and 10 on placebo)
• Weekly assessments
• Medication dosed twice daily, flexibly through week 5; held steady
last two weeks
• The primary outcome measures were the CGI; secondary outcome
measures included parent-assessed quality of life, the overt
aggression scale (OAS), and the conduct problems subscale of the
Conners' Parent Rating Scale (CPRS-CP).
• Final mean dose of quetiapine was 294 +/- 78 mg/day (range 200-
600 mg/day)
• Quetiapine was superior to placebo on all clinician-assessed
measures and on the parent-assessed quality of life rating scale.
No differences were found on the parent-completed OAS and
CPRS-CP.
– Connor et al, 2008
 Aripiprazole
• Flexible dose pharmacokinetic study of aripiprazole of 12 children
(6-12 years) and 11 adolescents (13-17 years) with Conduct
Disorder and a score of 2-3 on the Rating of Aggression Against
People and/or Property (RAAPP) scale
• Open label, 15-day, 3 site trial with optional 36 month extension
• Dose: <25 kg = 2 mg/day; 25 – 50 kg = 5 mg/day; >50 – 70 kg =
10 mg/day; >70 kg = 15 mg/day
• Due to vomiting and sedation, revised to 1 mg, 2 mg, 5 mg, and 10
mg/day
• Both children and adolescents demonstrated improvements in
RAAPP scores and CGI scores
• Adverse events similar to those in adults
• Findling et al, 2009
 Depakote
• 20 outpatient children and adolescents (ages 10-18) with a disruptive behavior disorder
(ODD or CD). They received 6 weeks of Depakote and 6 weeks of placebo by random
assignment. At the end of phase 1, eight of 10 subjects had responded to Depakote; zero
of 10 had responded to placebo. Of the 15 subjects who completed both phases, 12 had
superior response taking Depakote.
– Donovan et al, 2000
• Randomized 7-week trial of 71 adolescent boys with CD were treated with Depakote in a
controlled but open label fashion. Subjects were all adolescent males with at least 1 crime
conviction and were randomized into high- and low-dose conditions and were openly
managed by a clinical team. Those who received the high-dose condition were rated by
blind evaluators as having a statistically significant improvement (on CGI) over those
who received the low-dose condition. Self-reported weekly impulse control was
significantly better in the high-dose condition (p <.05), and association between
improvement in self-restraint and treatment condition was of borderline statistical
significance (p <.06). Parallel analyses comparing outcome by blood drug level achieved
strengthened the results.
– Steiner et al, 2003
• 12-week, open-label trial with Depakote in 24 bipolar offspring, 6-18 years of age (mean
age = 11.3 years; 17 boys), with mixed diagnoses of major depression, cyclothymia,
ADHD, and ODD. The Overt Aggression Scale (OAS) was used to measure aggression in
4-week intervals. 71% of subjects were considered responders to treatment. Serum
Depakote level did not correlate with treatment response. Thus, these children who are at
high risk for bipolar disorder experienced an overall decrease in aggressive behavior in
response to Depakote. Age or gender did not predict a positive response.
– Saxena et al, 2006
 Trends in the Use of Antipsychotics
• This study looked at national trends and patterns in antipsychotic treatment of youth
seen by physicians in office-based medical practices nationally.
• Analysis of national trends of visits (1993-2002) that included prescription of
antipsychotics, and comparison of the clinical and demographic characteristics of visits
(2000-2002) that included or did not include antipsychotic treatment.
• Data was drawn from patient visits by persons 20 years and younger from the National
Ambulatory Medical Care Surveys from 1993 to 2002.
• In the United States, the estimated number of office-based visits by youth that included
antipsychotic treatment increased from approximately 201,000 in 1993 to 1,224,000 in
2002. From 2000 to 2002, the number of visits that included antipsychotic treatment
was significantly higher for male youth (1913 visits per 100,000 population) than for
female youth (739 visits per 100,000 population), and for white non-Hispanic youth
(1515 visits per 100,000 population) than for youth of other racial or ethnic groups (426
visits per 100,000 population). Overall, 9.2% of mental health visits and 18.3% of
visits to psychiatrists included antipsychotic treatment. Mental health visits with
prescription of an antipsychotic included patients with diagnoses of disruptive behavior
disorders (37.8%), mood disorders (31.8%), pervasive developmental disorders or
mental retardation (17.3%), and psychotic disorders (14.2%).
• In sum, antipsychotic medications were prescribed to 1,438 per 100,000 children and
adolescents in 2002, up from 275 per 100,000 in the two-year period from 1993 to
1995.
– Olfson et al, 2006
 Shatkin’s Menu
• Identify and aggressively treat all other Axis I
disorders
• Provide all appropriate behavioral modification
treatments
• Start with the least invasive treatments:
– Maximize current treatments (e.g., for ADHD,
anxiety, mood)
– Alpha-2 agonists
– Antipsychotics
– Mood Stabilizers
– Polypharmacy
 Treatment (4)
• Multisystemic Therapy (MST)
– Shown effective in reducing antisocial behavior
– Possibly cost effective in the long-run
– Intensive treatment aimed at addressing risk at
individual, family, peer, school, and neighborhood
levels
– Components include:
• PMT
• Classroom social skills training
• Playground behavior program
• Systematic communication between teachers & parents
 Prevention
• Early intervention for children at risk
• School based interventions
• A primary risk factor consistently singled-
out is parenting (parenting behavior,
psychopathology, and genetic
contributions), which provide a useful
initial focus for intervention and prevention