Chelsea-DMDD-Presentation-2014

Download Report

Transcript Chelsea-DMDD-Presentation-2014

Disruptive Mood Dysregulation
Disorder (DMDD)
Chelsea Wiener
Part 1
DMDD and the DSM V
DMDD Diagnostic Criteria: DSM V
A. Severe recurrent temper outbursts (verbal or
behavioral aggression) “grossly out of proportion in
intensity or duration”
B. Temper outbursts inconsistent with development
level
C. Outbursts occur average of 3+ times/week
D. Mood in-between outbursts is irritably or angry most
of the day, nearly every day
E. A-D present 12+ months. No 3+ month period
without all of the symptoms
F. A+D present in at least 2/3 settings (home, school,
peers) and severe in at least one setting
DMDD Diagnostic Criteria: DSM V
G. Diagnosis not made before age 6 or after age 18
H. Age of onset for A-E before 10 years old
-No time period lasting more than a day when
full symptom criteria met for manic or hypomanic
episode
J. Symptoms not solely during major depressive disorder,
and not better explained by another mental disorder
-diagnosis cannot coexist with ODD
K. Symptoms cannot be attributed to substance use or
another medical or neurological condition
DMDD Diagnostic Features: DSM V
• Core feature: “chronic, severe persistent
irritability”
– Temper outbursts
– Irritable angry mood in-between outbursts
• vs. pediatric bipolar: distinct manic episodes
DMDD Prevalence: DSM V
• Unclear estimates for full DMDD criteria
• Estimates for chronic and severe irritability:
– 6 mo.- 1 year period= 2-5%
• Higher in males and school age children
– (vs. bipolar: gender balance more equal)
DMDD Development & Course: DSM V
• Onset of symptoms before 10 years old (cannot be
diagnosed before 6 years old)
• ~1/2 children presenting with severe chronic irritability
meet criteria for DMDD 1 year later
• Later Risks:
– Depression and anxiety in adulthood
– Less evidence for development of bipolar disorder later in
life
• DMVDD vs. Bipolar
– Bipolar rates low prior to adolescence (less than 1
percent); DMDD more common prior to adolescence and
become less common over time
Risk and Prognostic Features: DSM V
• Temperamental
– Irritability prior to diagnosis
– May also have symptoms for ADHD, anxiety,
depression
• Genetic + Physiological
– Risks for both DMDD (chronic irritability) and bipolar:
• Similar familial rates of anxiety, depression, and substance
use
• Similar face-emotion labeling deficits
• Compromised decision making and cognitive control
– Risks for DMDD (chronic irritability) alone:
• Dysfunction in attention related to emotional stimuli
Consequences of DMDD- DSM V
• Chronic severe irritability associated with:
– Problematic relationships
• Family, classmates, friendships
– Trouble in school
– Dangerous actions, suicide attempts, aggression,
psychiatric hospitalization
• Common with pediatric bipolar as well
Differential Diagnosis for DMDD
*Bipolar
-episodic
-manic episodes include cognitive, behavioral and physical symptoms,
and sometimes elevated mood and grandiosity
-cannot be dually diagnosed; cannot be diagnosed with DMDD if ever
manic for a day
*ODD
-DMDD children often have ODD symptoms, but less so vice versa
-15% children who meet ODD criteria meet DMDD criteria
-only DMDD diagnosis is made
-DMDD has recurrent severe outbursts
-DMDD has “severe impairment” in at least one setting, and impairment
in a second setting
Differential Diagnosis for DMDD
ADHD (can be dually diagnosed)
Depression (can be dually diagnosed)
-if irritability only during depressive episodes, then DMDD diagnosis not made
Anxiety disorders (can be dually diagnosed)
-if irritability only when experiencing anxiety, then DMDD diagnosis not made
Intermittent explosive disorder
-DMDD includes irritability in-between outbursts
-IED needs 3 mos. active symptoms for diagnosis vs. 12 mos. For DMDD
Autism spectrum
-if outbursts are only in relation to disturbed routines as part of autism spectrum,
no DMDD diagnosis made
Comorbidity
• Highly comorbid
• Strongest overlap with ODD
– Only DMDD diagnosis made
• Comorbid with mood, anxiety, autism
spectrum syndromes and symptoms
DSM V Schematic
Chronic
irritability
Risk For:
Temperament
Symptoms for:
ODD, ADHD,
anxiety, MDD
DMDD
Familial anxiety,
depression,
substance use
Secondary Features:
Genetic/Physio
logical
Face emotion
labeling
differences
Depression, anxiety, suicidality,
severe aggression, dangerous
behavior, psychiatric
hospitalization
Attention/cogni
tion differences
Primary Features:
severe, chronic
irritability
temper tantrums
Problematic relations with
others (peers, family), poor
performance in school, low
frustration tolerance,
dangerous behaviors,
suicidality
Part 2: Development and Prevalence of
DMDD
• Development of DMDD
– Development of Severe Mood Dysregulation
Disorder (SMD)
• DMDD Predictors, Prevalence, Comorbidity
• SMD Prevalence, Comorbidity, Course
Part 2: Development and Prevalence of
DMDD
• Development of DMDD
– Development of Severe Mood Dysregulation
Disorder (SMD)
• DMDD Predictors, Prevalence, Comorbidity
• SMD Prevalence, Comorbidity, Course
Development of DMDD: pediatric bipolar
disorder and Severe Mood Dysregulation
Disorder
• Large increases since 1990’s of new pediatric BP cases (Zepf
& Holtmann, 2012)
– Children being diagnosed without characteristic episodes (at
least 1 week mania, 4 days hypomania)
– Can be lead to problems of lifelong medication (Marguiles et al.,
2012)
development of Severe Mood Dysregulation (SMD) proposed by
Leibenluft et al. (2003)
• Probability of SMD children developing manic or hypomanic episode
50x lower than pediatric BP children (Stringaris et al., 2010)
• SMD children found to have higher ADHD and ODD comorbidity rates
(82.1%, 78.6% respectively) than BP children (45.2%, 25.8%)
(Stringaris et al., 2010)
Development of DMDD: Severe Mood
Dysregulation Disorder
Leibenluft et al. (2003)
A. Age 7-17 yrs. old
– Onset before 12 yrs.
B. Abnormal mood (anger or sadness) at least half the day on most days
– noticeable to others
C. Hyperarousal
– at least 3: insomnia, agitation, distractibility, racing thoughts, pressured
speech, intrusiveness
D. Increased reactivity to negative emotional stimuli
– E.g. temper tantrums, verbal rages, aggression to people or property
• Average 3+x/week for past 4 weeks
E.
F.
B-D present for a least 12 months (including current) and no 2 month
remission
Severe symptoms in at least one setting (school, home, peers), and at
least mild symptoms in another setting
SMD Diagnosis: Exclusions
A. Elevated mood, grandiosity/inflated self-esteem,
decreased need for sleep (episodic)
B. Symptoms occur in distinct periods (>4 days)
C. Schizophrenia, schizophreniform disorder,
schizoaffective illness, pervasive developmental
disorder, PTSD, substance abuse in past 3
months
D. IQ<80
E. Symptoms result of drug, abuse, medical or
neurological condition
Concerns regarding development of
DMDD
• More juvenile diseases may lead to more
pediatric medication
• Lack empirical support for DMDD in particular
(support for SMD)
• Not 100% overlap between SMD and DMDD
– Hyperarousal component of SMDD
– Different age onsets
– One study found 47.4% DMDD children met SMD
criteria; 58.1% SMD met DMDD (Dougherty et al.,
2014)
Part 2: Development and Prevalence of
DMDD
• Development of DMDD
– Development of Severe Mood Dysregulation
Disorder (SMD)
• DMDD Predictors, Prevalence, Comorbidity
• SMD Prevalence, Comorbidity, Course
DMDD Prevalence and Comorbidity
Copeland et al. (2013)
– Looked at 3 previous large scale studies and calculated rates of
DMDD using symptoms endorsed via psychiatric interview
– Ages 2-17*
• Prevalence
– 3 month rate: .8-3.3%
• .8-2.9% if use exclusion criteria with other disorders
• More common in pre-schoolers*
– Temper tantrums (especially in pre-schoolers) and negative
mood were most common symptoms endorsed
– Age onset X<10: no difference on prevalence rate when older
DMDD Prevalence and Comorbidity
• Comorbidity
– Most comorbidity with depressive disorders and ODD
• Depressive disorders
– Odds ratio: 9.9-23.5
» Among those with depression, 11.8-23% had DMDD
• w/o depression: .8-2.9% had DMDD
» Among those with DMDD, 12.4-35.8% had depression
• w/o DMDD: 1.4-3.2% had depression
• ODD
– Odds ratio: 52.9-103.0
» Among those with ODD, 23-37.7% had DMDD
• w/o ODD: .4-1% had DMDD
» Among those with DMDD, 57.4%-70.6% had ODD
• w/o DMDD: 2.2-3.8% had ODD
– DMDD diagnosed alone 8%(preschoolers)-38% of the time
DMDD Correlates and Predictors
Dougherty et al. (2014)
– Interviewed children at 3 yrs. old then 6 yrs. old
• Prevalence: 8.2% (full criteria)
– Didn’t take into account exclusions for other disorders
(e.g. mania, IED)
•
•
•
•
•
13.2% comorbid depressive disorder
13.2% comorbid anxiety disorder
10.5% ADHD
55.3% ODD
39.5% DMDD only
DMDD Correlates and Predictors
• DMDD predictors:
– ODD
– ADHD
– Maternal CBCL-DP classification
• Focus on attention problems, anxious/depressed feelings, aggressive behavior
– Lower peer functioning
• Rated by teacher
– Higher surgency (rated by mom)
• “high-intensity pleasure, impulsivity, activity, low shyness”
• Child behavior questionnaire
– Lower effortful control (rated by mom and dad)
• “inhibitory control, attention focusing, low-intensity pleasure”
– Higher child negative emotional intensity (rated by teacher)
– Parental lifetime substance use disorder
– Greater parental hostility
• Observed in lab
DMDD Stability and Comorbidities
• Axelson et al. (2012)
– 706 children (6-12 yrs.) from Longitudinal Assessment of
Manic Symptoms Study
– Retrospective DMDD diagnosis
• Didn’t exclude ODD+bipolar
– Intake:
• DMDD present in 26% of participants, more common in those with
elevated manic symptoms
• DMDD+ vs. DMDD– Higher DBD rates, dysthymia, elimination disorders, ADHD (not bipolar)
for DMDD+
– Multivariate model: ODD Odds Ratio: 68.7; CD Odds Ratio: 77.8
– didn’t differ on biological parent depression, bipolar, anxiety, psychosis,
substance use disorder, or CD
DMDD Stability and Comorbidities
– 1 Year Follow Up DMD Stability:
• 53% of those who met DMDD at intake did so a year
later
• 64% of those who met DMDD at 1 yr. follow up had
DMDD at intake
– 2 Year Follow Up DMDD Stability:
• Of those who met DMDD criteria at least 1 time, 19%
met all 3 times
– vs. of those with ADHD at least 1 time, 61% had all 3 times
*questions of stability
DMDD Stability and Comorbidities
•
DMDD at intake not associated with increased risk for later bipolar, anxiety,
psychosis, CD, depressive disorders
•
71% with ODD/CD had DMDD (3% without ODD/CD had DMDD)
– Intake:
•
•
•
•
•
58% of ODD children had DMDD
61% of CD children had DMDD
96% DMDD children had ODD or CD
96% DMDD met ODD or CD vs. 40% BP had comorbid ODD or CD
77% DMDD+ met ADHD and ODD/CD
•
44% of those with ADHD had DMD, 23% without ADHD had DMDD
•
No differences for MDD, Bipolar, Anxiety
*questions of comorbidity with ODD and CD
*population considerations
DMDD Stability and Comorbidities
Part 2: Development and Prevalence of
DMDD
• Development of DMDD
– Development of Severe Mood Dysregulation
Disorder (SMD)
• DMDD Predictors, Prevalence, Comorbidity
• SMD Prevalence, Comorbidity, Course
Prevalence, Co-occurence and Course
of SMD
Brotman et al. (2006)
• Used participants from Great Smoky
Mountains Study (community sample)
• Looked at modified SMD
– Chronically irritable, angry, depressed
– Excessive reactivity 3+/week
– Hyperarousal
• Insomnia, pressured speech, distractibility, physical
restlessness, racing thoughts, intrusiveness
Prevalence, Co-occurence and Course
of SMD
• Lifetime prevalence 3.3% for 9-19 yrs. old
• Co-occurrence at time first met SMD criteria:
– 67.7% had co-occurrence of another disorder
•
•
•
•
•
26.9% ADHD
25.9% CD
24.5% ODD
14.7% anxiety
13.4% depression
Prevalence, Co-occurence and Course
of SMD
• SMD at Wave 1 (mean age~10.6) predicted
depressive disorders at last wave (mean
age~18.3)
– Odds Ratio: 7.2
– Depressive disorders at Wave 1 didn’t predict
depressive disorders at last wave
– Not predictive of ADHD, CD, ODD, substance
abuse, anxiety
Development and Prevalence of
DMDD: Review
• DMDD Development:
– Increased in diagnosis of pediatric BP without distinct manic
episodes  SMD (includes hyperarousal component)  DMDD
• DMDD Prevalence ~ 1-8%
– Common comorbid conditions: ADHD, depression, ODD
• ADHD comorbidity estimates may vary widely based on sample used
– Diagnostic stability unclear
• DMDD Predictors
– ODD, ADHD, temperament, parent factors
• SMD prevalence ~3%
• SMD predictive of later depressive episodes
Part 3: DMDD Research
• Emotional Labeling/Emotional Differences
• Neural Differences
• Treatment
Part 3: DMDD Research
• Emotional Labeling/Emotional Differences
• Neural Differences
• Treatment
Face Emotion Labeling Deficits- SMD
vs .BD
Rich et al. (2008)
• Participants: NP BD (have had manic or
hypomanic episode), SMD, NC
• Emotional expression multimorph task (morph
task)
– Gradations of facial emotions
• 100% neutral to 100% expressive
– Happiness, surprise, fear, sadness, anger, disgust
– Participants can “stop” at any point and provide
answer (correct identification), then continue and
change answer
Face Emotion Labeling Deficits- SMD
vs. BD
• Morph task results:
– BD and SMD children needed more morphs before
first responding (regardless of correct response),
and responding correctly
• Social functioning and morph task results:
• SMD: worse family function (measured by LIFE scale)
related to worse recognition r = -.71
• BD: poorer social reciprocity (measured by SRS) with
poor recognition r = -.48
Face Emotion Labeling Deficits- SMD
vs. BD
Guyer et al. (2007)
• Compared the following groups (7-18 yrs. old) on
a facial emotion labeling task:
– BD, SMD, ANX/MDD, ADHD/CD, control
• ANX/MDD: Generalized anxiety, social phobia, separation
anxiety, or major depression
• High and low intensity expressions of happiness,
sadness, anger, fear.
• Results: SMD and BD made more errors than
other groups (but did not differ from each other)
Attentional Differences to Emotional
Stimuli- SMD vs. BD
Rich et al. (2010)
• Assessed SMD, BD, and NC (~10-15 yrs. old) on
“impact of emotional stimuli on attention”
• Emotional Interrupt Task:
– Fixation point  emotional picture (negative,
positive, neutral)  target (circle or square) 
picture  blank screen
• Press left button if circle, right if square
– reaction time
Attentional Differences to Emotional
Stimuli- SMD vs. BD
Attentional Differences to Emotional
Stimuli- SMD and BD
• Results:
– Between-groups response time differences
• BD slower to respond than NC after seeing all pictures
• SMD slower to respond than NC after neutral pictures
– Within-groups response time differences
• NC and BD significantly slower to respond after
negative and positive pictures vs. neutral pictures
• ***SMD did not vary based on emotion
– BD and SMD lower accuracy than NC
Attentional Differences to Emotional
Stimuli- SMD and BD
• Attention interference scores: subtract neutral
RT from neg./pos. RT
– SMD lower RT interference (regardless of
comorbidities) than BD and control for both
positive and negative pictures
• SMD RT interference for negative pictures
related to impaired peer relationships (r=0.35), and impaired social reciprocity (r=-0.47)
Emotional Labeling/Emotional Differences: A
Review
• SMD children more time to correctly facial
expressions
• Make more errors in identifying correct facial
expressions
• Emotional stimuli have less effect on attention
Part 3: DMDD Research
• Emotional Labeling/Emotional Differences
• Neural Differences
• Treatment
Amygdala Activation and Emotional
Processing
Brotman et al. (2010)
• Compared children with SMD, BP, ADHD, and NC
on amygdala activation during emotional
processing of neutral faces using fMRI
• 8-17 yrs. old
• Emotional face paradigm:
– Happy, angry, fearful, and neutral faces
– Passive viewing of face, rate how hostile (perceived
threat), subjective fear (how afraid), and nose width
Amygdala Activation and Emotional
Processing
• Results:
– BP and SMD more rated more fear for neutral faces than NC
– Activation differences in left amygdala during fear+nose-width
rating contrast:
• ADHD hyperactivation vs. NC, BP, and SMD
• SMD hypoactivation vs. NC, BP, ADHD
– No differences in left amygdala activation during hostility and
nose-width rating contrast
– Activation differences in left amygdala during nose width vs.
fixation trials
• SMD hyperactive vs. BP, ADHD, NC
• NC hypoactivation vs. BP And ADHD
*even though SMD rated faces are more fearful, showed under
activation of amygdala
Neural Responsiveness to changes in
facial expression
Thomas et al. (2012)
• 8-18 yrs. old BD, SMD, NC
• Pictures went from neutral to 100% angry, and
neutral to 100% happy
– 25% increments
– Nose width and hostility ratings
Neural Responsiveness to changes in
facial expression
• Amygdala activation analysis
– NeutralAngry
• Left amygdala differences
– NC had an increase in amygdala activation as anger
increased, BD and SMD did not
– NeutralHappy
• No differences
*again, amygdala underactivation for SMD
Neural Responsiveness to changes in
facial expression
• Whole brain analysis
– Neutral Angry
• Left posterior cingulate (LPC): NC more activation with
increased anger
– Authors suggest more effortful processing
– LPC activated by emotional stimuli and connected to
amygdala and other regions
Neural Responsiveness to changes in
facial expression
• Whole brain analysis
– Neutral Happy
• Main effect of group on right inferior parietal lobule (brodmann
area), left middle occipital gyrus and fusiform gyrus, right middle
occipital gyrus and cuneus, and left middle/superior frontal gyrus.
– BD had more negative slope than SMD and NC (except left middle
occipital gyrus)
» BD children: increase expressions of happiness associated with
decrease in activation
– SMD had a more positive slope than NC for all
» SMD children: increase in expressions of happiness associated with
increase in activation
*these brain these brain regions associated with emotional processing, face
processing, and attention
Neural Responses to Frustration
Deveney et al. (2013)
• 8-17 yrs. old.
• SMD (met criteria for DMDD) vs. NC on Posner
spatial cue task
– Includes monetary rewards, and frustration
• Two squares cue in one square target
– Respond to target location, cue predicted 75% of time
• Frustration portion:
– For one section of task, computer gave feedback that
response was “too slow” 60% of time regardless of speed
Neural Responses to Frustration
Neural Responses to Frustration
• Results:
– SMD children reported more frustration at end of frustration task vs. NC
– During frustration task SMD responded more slowly than NC on invalid trials
– Amygdala analysis:
• SMD less activation in left amygdala on negative feedback trials
• SMD within group differences: less activation in left amygdala on negative vs. positive
feedback trials (no difference for NC)
– Striatum analysis:
• SMD less activation in left and right striatum during negative feedback trials
• SMD less activation during negative vs. positive feedback trials (not seen in NC)
– Whole brain analysis:
• SMD less activation during negative feedback in parietal, parahippocampal, and
thalamic/cingulate/striatal regions
• SMD less activation in these regions during neg. vs. pos. feedback (not seen in NC)
Neural Responses to Frustration
• Implications
– slower RT time during frustration task may be related
to difficulty shifting spatial attention from cue
(involvement of parietal hypoactivation)
*Attention allocation skills important for emotional
regulation
– possibility of decreased striatal response during
negative feedback being related to reward processing
• Outcome worse than expected  experience as more
frustrating because unexpected and averse links to
exaggerated responses to frustrating events
Neural Responses: SMD vs. BP
Rich et al. (2011)
• Neural response differences: SMD vs. BD vs.
NC on Affective Posner task
• Results:
– SMD reported feeling more aroused (agitated)
than BD and control during negative feedback
– SMD and BP reported more unhappiness
throughout task
Neural Responses: SMD vs. BP
Neural Responses: SMD vs. BP
Neural Responses: SMD vs. BP
– Left anterior cingulate cortex (ACC):
• Negative feedback: SMD > control
• Positive feedback: Control > SMD
– Medial frontal gyrus (MFG):
• Negative feedback: SMD > control
• Positive feedback: Control > SMD
– Superior frontal gyrus (SFG):
• Negative feedback: BD > SMD and control
• Positive feedback: no differences
– Insula:
• Negative feedback: SMD and control > BD
• Positive: BD > SMD
– Supplementary motor area (SMA):
• Negative feedback: control > SMD
• Positive feedback: BD> SMD and control
Neural Responses: SMD vs. BP
• Implications:
– ACC, PFC, Insula: related to frustration
– ACC and MFG: related to evaluating, resolving,
and monitoring emotional conflict
– SFG: related to executive attention
– BA 6 (in SMA): cognitive activity
– Insula: processing negative and positive affect
*greater arousal in negative situations
Neuropsychological test performance:
SMD vs. ADHD
Uran & Kılıç (2014)
• Participants:
– 7-18 yrs. old. referred to University clinic
– Compared SMD vs. ADHD vs. NC on neuropsychological test
– Neuropsychological tests:
• Wisconsin card sorting task (WCST)
– Evaluates planning, searching, shifting cognitive sets, cognitive flexibility
• Stroop task
– Selective attention and response inhibition
• Trail making task
– Visual attention and task switching
• Controlled oral word association test
– Verbal fluency and reasoning
• Controlled oral word association test
– Verbal fluency and reasoning
• Category naming test (CNT)
– Producing words, attention, set shifting
Neuropsychological test performance:
SMD vs. ADHD
– Performance on neuropsychological tests was
comparable between ADHD and SMD participants
• ADHD < control on measures of WCST, TMT, Stroop,
COWAT
• SMD < control on COWAT
– Further comparisons of SMD vs. ADHD
• Parents and teachers rated SMD higher in hyperactivity,
social problems, impulsivity, emotional reliability
Neural Differences: A Review
• SMD hypoactivation of amygdala with fear-inducing faces
and angry faces
• Different brain activation patterns when viewing
expressions of happiness in areas of brain related to
emotional processing and attention
• Different brain activation patterns during negative feedback
in areas of the brain related to emotional conflict,
executive attention, cognition, processing affect
• Greater reports of frustration, negative feelings, and
arousal during frustration/attention tasks
• Greater difficulty in attention deployment
• SMD children perform comparably to NC children on
multiple neuropsychological tests
Part 3: DMDD Research
• Emotional Labeling/Emotional Differences
• Neural Differences
• Treatment
Treatment for SMD: Lithium?
Dickstein et al. (2009)
• Why Lithium?
– Irritability and aggression
• Participants: 7-17 yrs.
• Weaned off medication for 4 half lives , 2
weeks of placebo/hospitalization  evaluated
for SMD, if criteria still met randomized to
lithium or placebo for 6 weeks
Treatment for SMD: Lithium?
• Results:
– After placebo period: 25 randomized, 20 no longer
met criteria for SMD
– Clinical Global Impressions Scale
• No between groups differences regarding CGI < 4 (improved,
much improved, or symptom free)
– 3/14 lithium and 1/11 placebo
– Positive and Negative Syndrome Scale Factor 4
– Measures excitement, hostility, uncooperativeness, poor impulse
control
• No between group differences
– Little evidence for metabolite differences
Treatment for SMD: Lithium?
Treatment for SMD: Risperidone?
Krieger et al. (2011)
• 21 participants
– 19 completed full 8 week study
– Baseline, 2 week, 4 week, 6 week, 8 week
evaluations
– Mean: 10 yrs. old
– Comorbidities:
• 71.4% ADHD, 66.7% anxiety disorders, 81% ODD
Treatment for SMD: Risperidone?
• Results:
– ABC Irritability (Irritability Scale of the Aberrant
Behavior Checklist)
• Baseline average: 25.89 (18+ is considered “severe
impairing irritability”)
• Significantly reduced over time
–
–
–
–
Week 2 mean: 12.03 (ES 1.39)
Week 4 mean: 15.48 (ES 1.51)
Week 6 mean: 12.29 (ES 1.77)
Week 8 mean: 11.28 (ES 1.83)
Treatment for SMD: Risperidone?
– Clinical Global Assessment Scale
• Significant reductions from baseline (mean = 4.53)
–
–
–
–
Week 2 mean: 2.85
Week 4 mean: 2.96
Week 6 mean: 2.69
Week 8 mean: 2.64
– Children’s Depression Rating Scale
• Significant reductions from baseline (mean=34.28)
–
–
–
–
Week 2 mean: 24.11
Week 4 mean: 26.40
Week 6 mean: 25.93
Week 8 mean: 22.50
Treatment for SMD+ADHD patients:
Methylphenidate and Behavior
Modification
Waxmonsky et al. (2008)
• 101 Participants from a Summer Treatment Program for ADHD
– Ages 5-12
– 2 hours academics a day, 7 hours recreation
– Some campers with SMD
• Behavior modification (BMOD) and medication
(methylphenidate/MPH) component
– High, low, and no BMOD
• Every 3 weeks, switch BMOD condition
– Placebo, .15 mg, .3 mg, .6 mg MPH condition
• Changed each day
• SMD group had Young Mania Rating Scale (YMRS) score of more
than 12 (to test concerns about stimulant use)
• Parents had skills training course at home
Treatment for SMD+ADHD patients:
Methylphenidate and Behavior
Modification
– BMOD Levels
• High: social skills training, reward/cost point system,
time-outs, report cards detailing behavior,
individualized behavior plans etc.
• Low: weekly contingency rewards (vs. daily in HBM),
behavior plans not individualized
• None: no contingent rewards
Treatment for SMD+ADHD patients:
Methylphenidate and Behavior
Modification
Treatment Conditions:
Treatment for SMD+ADHD patients:
Methylphenidate and Behavior
Modification
• Results:
– SMD group elevated ODD and CD ratings throughout camp
– Significant reduction in ADHD, ODD, and CD symptoms
over time for all groups (but no group X time interaction)
– ADHD ratings:
• 85% of SMD showed at least a 50% improvement in time following
activity rules (FAR), seatwork completed (SC), and non compliance
to staff requests (NC)
– For over half of SMD participants, it was low or medium medication with
an active BMOD condition
• FAR
– All MPH and BMD doses affected SMD and non SMD children comparably
with regards to FAR, percentage of seatwork completed, and non
compliance to staff requests
» Exception: .3 mg low intensity BMOD
Treatment for SMD+ADHD patients:
Methylphenidate and Behavior Modification
– Percent of Rules followed by dosage:
» Placebo
• Non SMD vs. SMD: 34.59/32.48%
» .15 mg
• Non SMD vs. SMD: 48.05/43.99%
» .3 mg
• Non SMD vs. SMD: 56.6/53.62%
» .6 mg
• Non SMD vs. SMD: 67.16/63.14
– Percent of Rules followed by behavior modification therapy condition:
» none:
• Non SMD vs. SMD: 34.59/32.48%
» low:
• Non SMD vs. SMD: 49/45.23%
» high:
• Non SMD vs. SMD: 54.4./51.79%
Treatment for SMD+ADHD patients:
Methylphenidate and Behavior Modification
• Medication side effects:
– No exacerbation of manic symptoms
– Side effects more frequent at .6 mg dose (11 ppl had to reduce2 SMD and 9 non SMD)
– SMD subjects: increase in trouble sleeping and being
withdrawn, but irritability ratings decreased
• YMRS Scores
• 8.3 (34%) point total improvement in SMD subjects
–
–
–
–
ODD cluster (47% of difference)
ADHD cluster (23% of difference)
Mania cluster (25% of difference)
Decline of 11 points (31%) in children depression rating scale revised
• Children Depression Rating Scale Revised: 34%
improvement
Treatment for SMD and ADHD: Group
Therapy
Waxmonsky et al. (2013)
• Participants:
– 7-12 years old boys
– ADHD and SMD (all taking medication)
• 9 week pilot trial, 7 families
• Therapy program: treatment of ADHD and
impaired mood (AIM)
– 9 week parent and child intervention (separate
interventions) ( 6 week follow up)
– At academic research center
– Used materials from 4 other interventions
Treatment for SMD and ADHD: Group
Therapy
– Parent sessions
• Behavior modification principles
• Improve relations, consistency, communication, praise
positive actions, appropriate time outs and
contingencies, recognize triggers etc.
– Child sessions
• Contingency management, problem solving skills,
emotion identification, cognitive “toolbox”
Treatment for SMD and ADHD: Group
Therapy
– Results:
• Children’s Depression Rating Scale- Revised
– Pre, post, and follow up means: 30.43, 23.57, 24.69
» Pre-Post treatment d = 1.17
» Pre-Follow up d = 1.26
– “clinically meaningful change”: decrease of 40% from baseline score
» 4 had shown baseline “clinically significant impairment”
• 2/4 showed clinically meaningful change at post, but not retained
at follow up
• Young Mania Rating Scale
– Pre, post, and follow up means: 14.71, 10.43, 9.71
» Pre-Post treatment d = 0.81
» Pre-Follow up d = 1.43
– “clinically meaningful change”: decrease of at least 25% from baseline score
» 6 had shown baseline “clinically significant impairment”
• 4/6 showed clinically meaningful change
Treatment for SMD and ADHD: Group
Therapy
– Behavior ratings
• Small effects of parent ratings of ADHD, ODD, and CD, not
maintained at follow up
– Impairment ratings
• Improvement of CGAS scores baseline to post (d = 2.17)
– Baseline mean: 47.86= “serious level of symptoms”
– Post mean: 66.43 = “mild to moderate symptom severity”
– Follow up mean: 53.57
– Parent behavior
• Greatest gains seen for reductions in corporal punishment
pre-follow up (d = 0.93)
– Baseline mean: 4.71
– Follow up mean: 3.50
Treatment: A Review
• Lithium not shown to be effective in treating SMD
• Risperidone shown to be effective
– Reduces irritability ratings
• Combination of Methylphenidate and Behavior
Modification effective in increasing rule-following
and decreasing externalizing problems for
comorbid SMD/ADHD children
• Parent and child interventions shown to reduce
depression and mania symptoms in ADHD/SMD
children
DMDD Research Schematic
medication
Labeling deficits,
different neural
responses
Differences in:
*amygdala
activation
ACC, MFG, SFG,
Insula, Striatal
Agitation,
irritability, low
frustration
tolerance
Hostility,
lifetime
substance
use
Emotion
Processing
Differences
Genetic/Physiol
ogical
Temperament
Parent Factors
Treatment
DMDD/
SMD
Primary
characteristic:
chronic
irritability
Behavior
modification
Risk for: mood disorders
Secondary Characteristics:
ODD behaviors
ADHD behaviors
hyperarousal
Vs. DSM V Schematic
Chronic
irritability
Risk For:
Temperament
Symptoms for:
ODD, ADHD,
anxiety, MDD
DMDD
Familial anxiety,
depression,
substance use
Secondary Features:
Genetic/Physio
logical
Face emotion
labeling
differences
Depression, anxiety, suicidality,
severe aggression, dangerous
behavior, psychiatric
hospitalization
Attention/cogni
tion differences
Primary Features:
severe, chronic
irritability
temper tantrums
Problematic relations with
others (peers, family), poor
performance in school, low
frustration tolerance,
dangerous behaviors,
suicidality
References
•
Axelson, D., Findling, R.L., Fristad, M.A., Kowatch, R.A., Youngstrom, E.A…. Birmaher, B. (2012). Examining the
proposed disruptive mood dysregulation disorder diagnosis in children in the longitudinal assessment of manic
symptoms study. Journal of Clinical Psychiatry, 73(10), 1342-1350.
•
Brotman, M.A., Rich, B.A., Guyer, A.E., Lunsford, J.R., Horsey, S.E. Reising, M.M.,… Leibenluft, E. (2010). Amygdala
activation during emotion processing of neutral faces in children with severe mood dysregulation versus adhd or
bipolar disorder. American Journal of Psychiatry, 167(1), 61-69.
•
Brotman, M.A., Schmajuk, M., Rich, B.A., Dickstein, D.P., Guyer, A.E., Costello, E.J…. Leibenluft, E. (2006).
Prevalence, clinical correlates, and longitudinal course of severe mood dysregulation in children. Biological
Psychiatry, 60, 991-997.
•
Copeland, W.E., Angold, A., Costello, E.J., & Egger, H. (2013). Prevalence, comorbidity, and correlates of dsm-5
proposed disruptive mood dysregulation disorder. American Journal of Psychiatry, 170(2), 173-179.
•
Deveney, C.M., Connolly, M.E., Haring, C.T., Bones, B.L., Reynolds, R.C., Kim, P…& Leibenluft, E. (2013). Neural
mechanisms of frustration in chronically irritable children. American Journal of Psychiatry, 170(10), 1186-1194.
•
Dickstein, D.P., Towbin, K.E., Van Der Veen, J.W., Rich, B.A., Brotman, M.A, Knopf, L.,… Leibenluft, E.L. (2009).
Randomized double-blind placebo-controlled trial of lithium in youths with severe mood dysregulation. Journal
of Child and Adolescent Psychopharmacology, 19(1), 61-73.
•
Dougherty, L.R., Smith, V.C., Bufferd, S.J., Carlson, G.A., Stringaris, A., Leibenluft, E., & Klein, D.N. (2014). DSM-5
disruptive mood dysregulation disorder: Correlates and predictors in young children. Psychological Medicine, 44,
2339-2350.
•
Guyer, A.E., McClure, E.B., Adler, A.D., Brotman, M.A., Rich, B.A., Kimes, A.S.,… Leibenluft, E. (2007). Specificity of
facial expression labeling deficits in childhood psychopathology. Journal of Child Psychology and Psychiatry,
48(9), 863-871.
•
Krieger, F.V., Pheula, G.F., Coelho, R., Zeni, T., Tramontina, S., Zeni, C.P., & Rohde, L.A. (2011). An open-label trial
of risperidone in children and adolescents with severe mood dysregulation. Journal of Child and Adolescent
Psychopharmacology, 21(3), 237-243.
•
Leibenluft, E. (2011). Severe mood dysregulation, irritability, and the diagnostic boundaries of bipolar disorder in
youths. American Journal of Psychiatry, 168(2), 129-142.
•
Leibenluft, E., Charney, D.S., Towbin, K.E., Bhangoo, R.K., & Pine, D.S. (2003). Defining clinical phenotypes of
juvenile mania. American Journal of Psychiatry, 160(3), 430-437.
•
Marguiles, D.M., Weintraub, S., Basile, J., Grover, P.J., & Carlson, G.A. Will disruptive mood dysregulation disorder
reduce false diagnosis of bipolar disorder in children? Bipolar Disorders, 14, 488-496.
•
Rich, B.A., Grimley, M.E., Schmajuk, M., Blair, K.S., Blair, R.J.R., & Leibenluft, E. (2008). Face emotion labeling
deficits in children with bipolar disorder and severe mood dysregulation. Developmental Psychopathology, 20(2),
529-546.
•
Rich, B.A., Brotman, M.A., Dickstein, D.P., Mitchell, D.G.V., Blair, R.J.R., & Lebenluft, E. (2010). Deficits in attention
to emotional stimuli distinguish youth with severe mood dysregulation from youth with bipolar disorder. Journal
of Abnormal Child Psychology, 38, 695-706.
•
Rich, B.A., Carver, F.W., Holroyd, T., Rosen, H.R., Mendoza, J.K., Cornwell, B.R…& Leibenluft, E. (2011). Different
neutral pathways to negative affect in youth with pediatric bipolar disorder and severe mood dysregulation.
Journal of Psychiatric Research, 45, 1283-1294.
•
Stringaris, A., Baroni, A., Haimm, C., Brotman, M., Lowe, C.H., Myers, F….& Leibenluft, E. (2010). Pediatric bipolar
disorder versus severe mood dysregulation: Risk for manic episodes on follow-up. Journal of the American
Academy of Child & Adolescent Psychiatry.
•
Thomas, L.A., Brotman, M.A., Muhrer, E.J., Rosen, B.H., Bones, B.L., Reynolds, R.C.,… Leibenluft, E. (2012).
Parametric modulation of neural activity by emotion in youth with bipolar disorder, youth with severe mood
dysregulation, and healthy volunteers. Archives of General Psychiatry, 69(12), 1257-1266.
•
Uran, P., & Kılıç, B.G. Comparison of neuropsychological performances and behavioral patterns of children with
attention deficit hyperactivity disorder and severe mood dysregulation. European Child & Adolescent Psychiatry.
doi: 10.1007/s00787-014-0529-8.
•
Waxmonsky, J., Pelham, W.E., Gnagy, E., Cummings, M.R., O’Connor, B., Majumdar, A… & Robb, J.A. (2008). The
efficacy and tolerability of methylphenidate and behavior modification in children with attention deficit/
hyperactivity disorder and severe mood dysregulation. Journal of Child and Adolescent Psychopharmacology,
18,6, 573-588.
•
Waxmonsky, J.G., Wymbs, F.A., Pariseau, M.E., Belin, P.J., Waschbusch, D.A., Babocsai, L.,… Pelham, W.E. (2013). A
novel group therapy for children with adhd and severe mood dysregulation. Journal of Attention Disorders. doi:
10.1177/1087054711433423.
•
Zepf, F.D., & Holtmann, M. (2012). Disruptive Mood Dysregulation Disorder. In J.M. Rey (Ed.), IACAPAP Textbook
of Child and Adolescent Mental Health (Section E.1). Retrieved from http://iacapap.org/wp-content/uploads/E.3MOOD-DYSREGULATION-072012.pdf