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

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 behavior2) Distinguish between Oppositional Defiant Disorder

and Conduct Disorder3) 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 delinquency5) 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 temper2) Often argues with adults3) Often actively defies or refuses to comply w/rules4) Often deliberately annoys others5) Often blames others for his/her mistakes or behavior6) Often touchy or easily annoyed by others7) Often angry and resentful8) 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 monitoring & discipline

child

conduct problems

Rejection by normal peers & academic difficulties

Delinquency

Commit-ment to deviant peer groups

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


• 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


• 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 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


• 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


• Puberty– Early physical maturation is associated with increased

problem behaviors in girls, not boys

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


• 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


• 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’dOne 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

Documents

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