Externalizing Behavior Disorders

1
Externalizing Behavior Disorders

• Jess P. Shatkin, MD, MPH
• Director of Education and Training
• NYU Child Study Center
• New York University School of Medicine

2

• Anyone can become angry, that is easybut to
  become angry with the right person, at the right
  time, for the right purpose, and in the right
  waythis is not easy.
• --Aristotle

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Learning Objectives

• Residents will be able to
• Identify normal from aberrant and disruptive
  childhood behavior
• Distinguish between Oppositional Defiant Disorder
  and Conduct Disorder
• Discuss 11 major risk factors for the development
  of Disruptive Behavior Disorders in children and
  adolescents and identify 3 protective factors
• Describe one model of delinquency
• Select appropriate treatments strategies for
  children and adolescents with Oppositional
  Defiant and Conduct Disorder

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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

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Oppositional Defiant Disorder

• Pattern of negativistic, hostile, defiant
  behavior lasting at least 6 months w/4 or more
  DSM-IV Criteria
• Often loses temper
• Often argues with adults
• Often actively defies or refuses to comply
  w/rules
• Often deliberately annoys others
• Often blames others for his/her mistakes or
  behavior
• Often touchy or easily annoyed by others
• Often angry and resentful
• Often spiteful or vindictive

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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

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Natural History

• Gender differences dont emerge until after 6 y/o
• More prevalent in males prior to puberty rates
  equalize (mf) 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)

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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

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Harry Potter and the Sorcerers 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
  parents fear of conflict with their child,
  leading to oppositional/defiant and manipulative
  behavior

10
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
• Aggression to people or animals
• Destruction of property
• Deceitfulness or theft
• Serious violations of rules

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Subtypes of Conduct Disorder

• Two subtypes, based upon age of onset, which
  differ in presenting symptoms, developmental
  course, prognosis, gender
• 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
• 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 malesfemales, but a lower ratio

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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

13
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

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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 _at_ OR 2.9)
• Common Axis I Comorbidities
• ADHD, LD, Communication D/O, Anxiety D/O, Mood
  D/O, SUDS

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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

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A Model of Delinquency
Middle Childhood
Early Childhood
Rejection by normal peers academic difficulties
child
Poor parental monitoring discipline
conduct problems
Late Childhood Adolescence
Commit-ment to deviant peer groups
Delinquency
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Child Biological Factors PossiblyContributing 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

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Child Biological Factors PossiblyContributing 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

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Child Biological Factors PossiblyContributing 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

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Child Functional Factors PossiblyContributing 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

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Child Functional Factors PossiblyContributing 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
  its known that empathy mediates aggressive
  behavior

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Child Functional Factors PossiblyContributing to
ODD CD (3)

• Puberty
• Early physical maturation is associated with
  increased problem behaviors in girls, not boys

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Psychosocial Factors PossiblyContributing 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

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Psychosocial Factors PossiblyContributing 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

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Psychosocial Factors PossiblyContributing 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

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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 Wonkas
  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-Loompahs infectious melodies
  punctuate the story and spell-out the cause of
  such problems (poor parental control)

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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

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Protective Factors

• The opposite of risk factors?
• 3 Protective Factors for ODD
• Good relations with at least one parent
• Good peer relations
• Good parental monitoring

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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

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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)

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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

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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 (n50) Malone et al, 2000
  (n40)
• 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

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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)

34
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

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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

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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)

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Risperidone contd

• 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.

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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

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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

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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 lt25 kg 2 mg/day 25 50 kg 5 mg/day
  gt50 70 kg 10 mg/day gt70 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

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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 lt.05), and association between
  improvement in self-restraint and treatment
  condition was of borderline statistical
  significance (p lt.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

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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

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Shatkins 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

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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

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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