Aggression, Violence and Psychopathology: A Developmental Approach

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Aggression, Violence and Psychopathology A
Developmental Approach

• Hans Steiner, MDProfessor, Division of Child
  Psychiatry Stanford University School of Medicine

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Disclosure Information

• Consultant for Abbott Laboratories, Janssen
  Pharmaceutica
• Receives research support from Abbott
  Laboratories, Astra Zeneca, Janssen
  Pharmaceutica, Pfizer, Inc., Wyeth-Ayerst, Solvay
  Pharmaceuticals, GlaxoSmithKline
• Speaker for Abbott Laboratories, Janssen
  Pharmaceutica, Pfizer, Inc., AstraZeneca

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Disclaimer

• All current psychopharmacologic treatments for
  aggression and its disorders in children and
  adolescents are off-label.

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The Current Lecture

• The aggression system
• Update on the psychopharmacology of juvenile
  aggression
• Meta-analysis of stimulants and aggression
• Relationship of aggression to psychiatric trauma
  and psychopathology
• Reactive/Affective/Defensive/ (RAD) Aggression
• Antikindling treatment of aggression based on
  this model
• Early developmental manifestations of RAD
  aggression

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The Aggression System
Event
Pragmatics Assertion, Aggression, Violence Striat
um
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Randomized, Placebo-Controlled Clinical Trials of
Medication for the Treatment of CD

• 13 studies, 559 subjects, 9 (8?) positive for
  medications, 4 (5?) equivocal
• Agents studied Li, DVPX, Risperidone,
  Haloperidol, Molindone, Methylphenidate (MPH),
  CBZ, Vitamins
• Average Duration 10 weeks, no long-term follow
  up, few comparative studies, small samples
• BUT antipsychotics are most commonly prescribed
  (60-80) for aggression, regardless of diagnosis

Steiner, January 2002
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Psychopharmacology of Aggression Effects of
Stimulants in ADHD A Meta-analysis

• 28 studies
• Criteria ADHD, peer reviewed, placebo-controlled,
  age lt18,scaled aggression
• 2 with MR and CD as primary diagnoses each rest
  were ADHD 75 comorbid with ODD,CD
• Average N24
• 88 boys ? age 9.7 (7.7-14.4)
• MPH in 75 (dose 24 mg/day) duration 13 days

Connor et al, 2002
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Psychopharmacology of Aggression Effects of
Stimulants in ADHD

• Overt aggression
• Clinician (d .77)
• Parent (d .57)
• Teacher ratings (d .93)
• All significant
• Presence of MR and CD/ODD reduces Effect Size
• AMPH and MPH equally effective (.8) PEM more
  (1.6)

Connor et al, 2002
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Psychopharmacology of Aggression Effects of
Stimulants in ADHD

• Covert aggression
• Clinician (d .81) significant
• Parent (d.37)
• Teacher ratings (d.54) not significant (but
  wide range, only seven studies)
• Drug type did not make a difference, duration and
  dose weakly contributed
• Overall sample age correlated positively with
  effect size no gender effects

Connor et al, 2002
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Psychopharmacology of Aggression Effects of
Stimulants in ADHD

• Conclusion Stimulants have significant effects
  on aggression (especially overt, especially when
  ADHD is primary diagnosis and not comorbid with
  CD, MR) and maybe in older subjects
• Limitations
• Not all double blind
• Short duration
• No long term follow-up
• Other comorbidities? PTSD, bipolar

Connor et al, 2002
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The Aggression SystemInfluences and Limits
Psychiatric Trauma related pathologies
Environment (e.g., substances, socialization,
education)
Aggression System
Development and Maturation (e.g.,
diversification of affect, intentionality,
cruelty)
Constitution (e.g., genetics, perinatal injury)
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Is there reason to think that trauma plays a role
in disturbances of aggression?

• Developmental epidemiological studies (Widom,
  1989)
• Community violence exposure studies (Osofsky,
  1995 Schwab-Stone, 1999)
• Clinical self report studies (Burton et al, 1994)
• Structured interview studies (Steiner et al
  1997 Cauffman et al 1998 Steiner et al 2002)
• Transcultural studies (Aichhorn, 1935 Rushkin
  et al, 2002)

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PTSD in DelinquentsWhat events do boys and
girls report?
PDI-R Results
of Subjects
Types of Trauma
?2 43.0 DF 4, p 0.001
Steiner et al, 1997
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PTSD in Female Incarcerated Delinquents 1997

X210.7 plt0.005
Cauffman et al, 1998
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PTSD in California Youth Authority Study REM-71
Factors Primary Appraisal - Defenses
Standard Scores
All ps lt0.05
Steiner et al, 1997
Cauffman et al, 1998
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PTSD in CYA Study WAI Factors Activation and
Secondary Appraisal
Standard Scores
All ps lt0.05
Steiner et al, 1997
Cauffman et al, 1998
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Structured Interviews in Incarcerated Youth
Externalizing and Internalizing Disorders

• Females (n140)
• Externalizing Disorders - 96
• Disruptive Disorders 94
• Substance Use 85
• Internalizing Disorders - 64
• Depression 24
• Anxiety 55

• Males (n650)
• Externalizing Disorders - 97
• Disruptive Disorders 95
• Substance Use 85
• Internalizing Disorders - 29
• Depression 8
• Anxiety 26

Steiner et al, 2002 new data (unpublished)
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Components of the Aggression System Which Should
Be Affected by Trauma

• Primary Appraisal Defenses YES Feldman,
  Araujo Steiner, 1996 Steiner, Garcia and
  Matthews, 1997
• Affective Activation Anxiety and Aggression
  often go together YES- Steiner, Garcia and
  Matthews, 1997 Cauffman et al, 1998 NEW DATA
• Secondary Appraisal Restraint, Impulse control
  is impaired as a function of trauma YES

This profile leads to reactive/affective/defensive
(RAD) aggression
Steiner et al, 2002 new data (unpublished)
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Clinical Subtypes of Aggression Form and Causal
Process
Aggression
Oppositional
Covert
Overt
Act
Premed- itated
Situa- tional
Reactive, Affective, Defensive
Process
Escalating
Explosive
Psychopathological
Steiner et al, 2002 new data (unpublished)
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How do we get from psychiatric trauma to
reactive/affective/defensive aggression?

• Eysenks antisocialization hypothesis high
  levels of anxiety in high criminogenic
  environments predict future maladaptive
  aggression in adolescents
• LeDouxs anxiety/active coping hypothesis trauma
  induced anxiety can be controlled by active
  coping (in this case of criminogenic
  environments involving aggression)
• Posts PTSD kindling hypothesis Repeated
  traumatization leads to increasingly facile
  affective activation which becomes a mixture of
  anxiety, depression, anger

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Divalproex Sodium in CD Design
Weeks 0-7 0 1 2 3 4 5 6 7

Measures
Best est. dx (open) X
CGI (O) X
WAI (Blind) DSS/RST X X X X X X X X
REM (B) F1/F2 X
YSR (B) Int/Ext X
HD/LDCD (B) X
CGI (B) X
High dose 1000 mg/d Low Dose ? 250 mg/d W O S E T H X X X X X X X X X X
Steiner, 2002
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Divalproex Sodium for the Treatment of Severe CD
in Boys

• Low ( 125 mg) and high dose (1000 mg) 7-week DBPC
  clinical trial
• Sample 70 boys consented, 61 completed 3 month
  protocol (7 weeks on medication) 58 had all
  outcome measures
• Multi-method, Multi-trait measures
• CGI-I Intent-to-treat 35 responded (53 in
  high dose vs. 8 in low dose condition)
• Significant differences in self rated slopes of
  weekly restraint
• No significant side effects (drowsiness, GI
  upset), easily tolerated

Steiner, 2002
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Different Patterns of Aggression Respond to
Divalproex Sodium

• 61 adolescent males into predominantly High
  Distress (HDCD) and Low Distress (LDCD) Conduct
  Disorders
• Low distress CD show predominantly premeditated
  aggression High Distress CD are predominantly
  RAD aggressive.
• In a 7 week RDBPC trial of DVPX we found that the
  HDCD had a more robust response to therapeutic
  doses of DVPX Sodium
• Responsive targets were observer rated CGI,
  weekly slopes of self reported Distress
  (decreased) and Restraint (increased)

New Poster APA, 2002
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HDCD and LDCD in Double-Blind, Placebo-Controlled
Divalproex Trial
Weekly Slopes of Restraint
Weekly Slopes of Distress
Standard Scores
Low Dose
High Dose
Low Dose
High Dose
2x2 ANOVA HD/LDCD effect p.049
2x2 ANOVA NS
Remsing L, Chang K, Saxena K, Silverman M,
Steiner H. Divalproex Sodium in Conduct Disorder
Response Rates and Aggression. , Scientific
Proceedings Of The Annual Meeting Of The APA, 
May 2002
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Predictors of Response to DVPX in CD
Likelihood ratio Chi Square (DF 5) 20.51, p0.001
Good Response
Restraint
Factor 2 (Mature) Defenses
Distress
Factor 1 (Immature) Defenses (OR 3.1, p0,046),
Acting Out!
Divalproex Sodium at 1000-1500 mg q d (OR16.3,
p0.002)
Week 0 Week 8
Silverman M, Remsing L, Saxena K, Chang K,
Steiner H. Trait and State predictors of Response
to Divalproex Sodium in Conduct Disorders. Annual
meeting of the American Academy of Child and
Adolescent Psychiatry, San Francisco, October 2002
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Divalproex in PTSD The Sample

• 12 boys
• Ages 14-17, mean 15.9 (SD0.9)
• Highly comorbid
• Conduct disorder (12)
• Mood Disorder (8)
• ADHD (6)
• Average number of diagnoses 4.8 (SD1.2)

Silverman M, Carrion V, Chang K, Matthews Z,
Peterson M, Steiner H Divalproex Sodium and
PTSD Treatment A Randomized Controlled Clinical
Trial, Scientific Proceedings Of The Annual
Meeting Of The American Academy Of Child And
Adolescent Psychiatry, 17 115,  2001
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Divalproex Study in PTSD Outcome by Blind Global
Clinician Ratings (Intent to Treat Analyses)
Total N12
RS 1-5
p 0.045 0.03 .1 0.02
Observer Ratings
Silverman M et al, Scientific Proceedings Of The
Annual Meeting Of The American Academy Of Child
And Adolescent Psychiatry, 17 115,  2001
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Divalproex Study in PTSD(Intent to Treat
Analyses)
Weekly Slopes of Distress
Weekly Slopes of Restraint
Total N12
R/S
p 0.025 0.02 .3 .03 .6
p .2 .3 .08 .5 .4
WAI Subscales
Silverman M et al, Scientific Proceedings Of The
Annual Meeting Of The American Academy Of Child
And Adolescent Psychiatry, 17 115,  2001
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Implications of DBPC trials in CD 2002Emerging
Pathways

• Lithium may be most applicable in prepubertal
  aggression with a reactive/affective/defensive
  profile
• Divalproex may be most useful in pubertal CD with
  a high affective component either to mood
  disorder or trauma especially chronic trauma
• Antipsychotics (risperidone haloperidol may be
  most helpful when executive cognitive functions
  are impaired (MR, PDD, psychosis)
• Stimulants should be considered when there is a
  comorbid attention deficit (caveat juvenile
  bipolar)

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The Developmental Model for Disruptive Behavior
Disorders
Time
Risk Factors
Protective Factors
Health
CD, ODD
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Observing Infants Aggression at 1 Year Teen
Mothers and Researchers Reports

• Sample of 60 teen mothers at high risk ,
  predominantly Hispanic, 33 boys and 28 girls
  followed from pre-birth, assessment at 13 months
• Variables maternal psychopathology, CAPI, PSI
  Reported infant aggression, negative emotional
  reactivity and emotion regulation Same infant
  variables observed
• Experimental tasks strange situation, Bailey
  testing

Gschwendt, Zelenko Steiner, 2002
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Observing Infants Aggression at 1 year Results

• In infants, negative affective reactivity,
  emotion regulation and aggression were
  significantly correlated by mothers and
  observers reports, separately (Spearmans 0.47
  to - .81, ps lt 0.05)
• Maternal depression, anxiety, CAPI and PSI
  correlated with mothers reports of infant
  aggression, negative affective reactivity
  (Spearmans 0.22 to 0.47, ps lt0.05) in infants
• Mothers reports correlated with observer ratings
  only if their own functioning was taken into
  account

Gschwendt, Zelenko Steiner, 2002
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Early Developmental Manifestations of
Reactive/affective/defensive Aggression
Anxiety, Depression, Parenting Stress, Abuse
Potential
Parent
Child
Negative affective reactivity, poor emotion
regulation, aggression
2002
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Trauma and Reactive/Affective/Defensive (RAD)
Aggression Summary APA 2002

• Traumatic Events are extremely common in the
  lives of maladaptively aggressive (MAA) youth
• PTSD is extremely common in MAA youth
• PTSD leads to faulty primary appraisal,
  anxious/angry activation and loss of self
  restraint reactive/affective/defensive
  aggression kindling
• Treatment with DVPX is effective in CD, even more
  effective in CD and PTSD
• Antikindling treatment seems to treat
  reactive/affective/defensive aggression good
  response is predicted by variables related to
  PTSD at baseline
• Early antecedents of reactive/affective/defensive
  aggression involve negative affect/ poor emotion
  regulation and aggression in the infant (by both
  observer and mothers reports and increased
  attribution of negative characteristics by the
  mother as a function of her anxiety and depression