Disruptive-Mood-Dysregulation-Disorder-Kirran

Report
Disruptive Mood
Dysregulation Disorder
Kirran Bakhshi
Child Psychopathology
October 2, 2013
What is…
Disruptive Mood Dysregulation
Disorder?
“Persistent irritability and frequent episodes of extreme
behavioural dyscontrol” (DSM-V, American Psychiatric Association,
2013)
University of Central Florida
DSM-V
University of Central Florida
What is this (and why do we care)?




a diagnosis added to the newly-released DSM-V, amid
much controversy
based on a cluster of symptoms previously called
‘severe mood dysregulation’
specifically for children
to reduce the threat of overdiagnosing (and
overtreating!) children for bipolar disorder (BD)
University of Central Florida
Criteria I





Severe recurrent temper outbursts, verbal and/or
behavioural, out of proportion in intensity or
duration to the situation
Outbursts inconsistent with developmental level
Outbursts occur ~3+/week
Mood between outbursts is persistently irritable
most of the day, almost every day, and is observable
by others
Criteria are present for at least 12 mos, in at least 2
settings (home/school/peers), and is severe in at least 1
setting
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Criteria II





Should only be diagnosed between 6-18 years, with age
at onset before 10 years
Criteria for a manic/hypomanic episode have never been
met
Does not occur exclusively during MDD, and is not better
explained by another disorder, effects of substance use,
or other medical/neurological condition
CANNOT COEXIST with: ODD, IED, BD
MAY COEXIST with: MDD, ADHD, CD, substance use
disorders
University of Central Florida
Clinical manifestations

IRRITABILITY

frequent temper tantrums


persistent irritable/angry mood


typically occur in response to frustration
most of the day, almost every day
Must be distinguished from episodic (typical) bipolar
disorder: no manic or hypomanic episodes in DMDD
University of Central Florida
Prevalence



Common in children presenting to mental health clinics,
although rates unknown in community
Overall 6 month-1 year period-prevalence: 2-5% of
children and adolescents
Rates higher in males and children (than females and
adolescents)

These are distinguishing features from bipolar disorder, where
rates are much lower prior to adolescence and steadily increase
into early adulthood, and where there is equal gender
prevalence
University of Central Florida
Course



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Age of onset: must be before 10 years; must have a
developmental age of at least 6 years
Use of diagnosis should be limited to 7-18 years
~1/2 will still meet criteria 1 year later
Very low risk of conversion to bipolar disorder, although
there is risk of developing depressive/anxiety disorders
later in adulthood
University of Central Florida
Risk factors
Temperamental
 Extensive history of chronic irritability, potentially even
qualifying for a diagnosis of ODD
 Many also meet criteria for ADHD and anxiety disorders,
or even MDD, with symptoms present at an early age
Genetic
 DMDD and BD do not differ in family-based risk, but both
have deficits in face-emotion labeling, decision-making,
cognitive control

DMDD: specific dysfunction has been shown when assessing
attention deployment in response to emotional stimuli
University of Central Florida
Functional consequences

Marked disruption in family & peer relationships

Low frustration tolerance: difficulty succeeding in school,
unable to participate in activities w/other children, trouble
initiating/sustaining friendships

Dangerous behaviour, suicidal ideation, suicidal
attempts, severe aggression, psychiatric hospitalization
common [although DSM-V states more research is
needed to document this]
University of Central Florida
Differential I: Bipolar disorders

Primary differential feature: longitudinal course of
symptoms

Bipolar disorders: episodic illness; discrete episodes of mood
perturbation that are different from the usual



During manic episode: onset/worsening of cognitive, behavioural,
physical symptoms that are different from the usual
DMDD: mood is persistent
Elevated/expansive mood, grandiosity: characteristic of
mania and bipolar disorders, but NOT DMDD
University of Central Florida
Differential II: ODD



Symptoms of ODD do occur in DMDD, but the opposite
is rarely true: there are not often symptoms of DMDD in
ODD
Most children who meet criteria for DMDD will also meet
criteria for ODD: due to criteria of severe and frequent
outbursts, and necessary impairment in at least 2
settings
However, even if criteria for ODD are met in DMDD, only
the diagnosis of DMDD should be given: mood
symptoms are prominent, as is risk for future
mood/anxiety disorders
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Differential III: ADHD, MDD,
anxiety disorders, ASD


Can be comorbid with ADHD, MDD, anxiety disorders
MDD


Anxiety disorders

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If irritability only present during the course of MDD or dysthymia,
DMDD should not be given
If irritability only present in exacerbation of anxiety disorder,
DMDD should not be given
Autism spectrum

Temper outbursts occur frequently, should not be considered
secondary diagnosis but part of ASD
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Differential IV: Intermittent
explosive disorder

Intermittent explosive disorder: may also present with
severe temper outbursts; however, no persistent mood
disruption in-between


Requires 3 mos of symptoms, while DMDD requires 12 mos
These disorders should NOT be comorbid
University of Central Florida
Comorbidity

Rates of comorbidity are very high: rare to find only
DMDD

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
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Strongest overlap with ODD
Wide range of comorbid illnesses: disruptive behaviour,
mood, anxiety, autism spectrum symptoms
In case of comorbid symptoms of bipolar disorder: only
BD diagnosed
In case of comorbid symptoms of ODD or IED: only
DMDD diagnosed
University of Central Florida
Model: DSM-V
Risk factors
o history of irritability
o emotional-processing
deficits
Core Features
o chronic and persistent
irritability
o temper tantrums
Secondary features
o impaired relationships with
family and peers
o problems in school
o ADHD, MDD, anxiety
disorders
University of Central Florida
Literature
University of Central Florida
Severe mood dysregulation & Ellen
Leibenluft

Ellen Leibenluft: senior investigator at
NIH & Associate Professor of Psychiatry,
Georgetown University School of Medicine

Spearheaded characterization and
diagnostic criteria for severe mood
dysregulation (SMD) in 2003

Widely involved in ongoing efforts to describe and further
understand the disorder and its deficits

Her lab studies both BD and SMD: structural MRI, fMRI,
DTI, MEG, genotyping, behavioural paradigms; clinical
treatment trials, psychological functioning, neural circuitry
University of Central Florida
Epidemiology & prevalence


There have been 2 studies to date looking at
epidemiology of either SMD (Brotman et al, 2006) or
DMDD (Copeland et al, 2013); both were retrospective,
both large samples
Lifetime prevalence of SMD among 9-19yo: 3.3%
(Brotman et al, 2006)

67.7% had comorbid axis I diagnosis

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ADHD: 26.9%; CD: 25.9%; ODD: 24.5%
Copeland et al, 2013: DMDD relatively uncommon after
early childhood

applying all of the DMDD criteria (especially duration) decreased
prevalence to ~1%
University of Central Florida
SMD & bipolar disorder: I

Category of SMD initially came out of desire to make
explicit the various phenotypes of bipolar disorder

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THE IMPORTANCE OF MAKING CORRECT DIAGNOSIS!
Done to optimize treatment plans, as well as to describe
a “relatively homogeneous population of patients with
mood disturbance, hyperarousal, and decreased
frustration tolerance” (Leibenluft, Charney et al, 2003)
Phenotypes may have different course and family history
However, the phenotypic populations are still likely to be
heterogenous
University of Central Florida
SMD & bipolar disorder: II

2 main phenotypes were characterized (Leibenluft,
Charney et al, 2003)


narrow BD phenotype: “[must] meet the full DSM-IV diagnostic
criteria for (hypo)mania, strictly construed, with the hallmark
symptoms of elevated mood or grandiosity and clear episodes
meeting the duration criteria”
broad BD phenotype: “chronic, nonepisodic illness that lacks the
hallmark symptoms of (hypo)mania but that shares with the
narrower phenotypes the symptoms of severe irritability and
hyperarousal”

Essentially, SMD = DMDD, except for the criteria of hyperarousal
(required for SMD but not DMDD)
University of Central Florida
Differentiating between SMD & BD

Several studies have investigated:

Familial risk (Brotman et al, 2007)
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Risk for mania at follow-up (Stringaris et al, 2010)
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Parents of children with BD are significantly more likely to have
been diagnosed with BD themselves than are parents of children
with SMD (r=0.25)
Children with SMD are unlikely to develop manic episodes at FU,
~2yr (1/84 SMD, vs 58/93 BD)
Cognitive flexibility (Dickstein et al, 2007)
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Ability to adapt to changing contigencies
BD and SMD children performed differently on two stages: simple
reversal (BD<SMD: r=0.22), compound reversal (BD~SMD), change
task reaction time (BD<SMD: r=0.21)
University of Central Florida
Emotional-processing deficits

Numerous studies looking at attention and emotionalprocessing in SMD, due to known deficits in BD

Face-emotion labeling:
Rich et al, 2008

Compared to HC, SMD
& BD both required increased
intensity of facial expressions
in order to identify the emotion
(r=0.37) but did not differ from
each other
University of Central
Florida
Fig 2. From
Rich et al, 2008: facial morphs for ‘disgust’
Emotional-processing deficits

Numerous studies looking at attention and emotionalprocessing in SMD, due to known deficits in BD

Affective prosody: Deveney et al,
2012
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Identifying the emotional tone of
verbal information
SMD made more errors than HC
(η2=0.05)
When broken down by medication:
unmedicated SMD made more
errors than HC (η2=0.07), but
medicated SMD did not differ from
HC (η2=0.03)
Fig 1. From Deveney et al, 2012: mean number
of errors (not differentiated by medication)
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Emotional-processing deficits:
amygdala activation

Numerous studies looking at
attention and emotionalprocessing in SMD, due to
known deficits in BD

Brotman et al, 2010: fMRI (BOLD
signal)
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
Face-emotion processing (w neutral
faces)
SMD: showed L amygdala
hypoactivation compared to HC, BD,
ADHD
Fig 1. From Brotman et al, 2010: mean
activation in L amygdala
University of Central Florida
Emotional-processing deficits:
amygdala activation

Numerous studies looking at
attention and emotionalprocessing in SMD, due to
known deficits in BD

Thomas et al, 2013
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Responses to emotional faces
SMD: increased activity in R
amygdala for all expressions (angry,
fearful, neutral)
compared to HC [no diff w/BD]
SMD: deactivation of posterior
cingulate cortex, posterior insula, IPL,
for fearful expressions only
Fig 1. From Thomas et al, 2013: % change in
R amygdala across all expressions
University of Central Florida
Emotional-processing deficits:
amygdala activation

Thomas et al, 2013:
Fig 2-4. From Thomas et al, 2013: % change in L posterior cingulate cortex & L IPL, respectively
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Emotional-processing deficits:
attentional bias

Numerous studies looking at attention and emotionalprocessing in SMD, due to known deficits in BD

Attentional bias to threat faces: Hommer et al, 2013


Tendency to allocate attention to threat is characteristic of anxiety
SMD showed attention bias towards threatening faces compared to
HC (d=0.54), and this did not differ between SMD with or without
comorbid anxiety disorder
University
Central
Fig 1. From Hommer et al, 2013:
Threatofbias
(ms) inFlorida
SMD and HC
Emotional-processing deficits:
attentional bias

Psychophysiological responses
during frustration task: Rich et al,
2007


SMD reported more arousal (ie.
frustration) during task, compared to
HC (r=0.25)
ERPs: SMD also showed a lower
N1 amplitude compared to HC and
BD (“indicates deficient attention”),
whereas the P3 amplitude in SMD
was similar to HC but different from
BD (impairments in executive
attention in BD but not SMD)
University of Central Florida
Figs 2 & 3.
From Rich et
al, 2007: P3 &
N1 amplitudes,
respectively, in
response to
frustration task
Emotional-processing deficits:
attentional bias
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Attention to emotional stimuli: Rich
et al, 2010: how attention is
affected by positive, negative and
neutral distractors
SMD showed decreased
interference from emotional
distracters (η2=0.03), compared to
BD (η2=0.17) & HC (η2=0.26)
[insinuating SMD less sensitive to
emotional stimuli]
SMD had decreased response
interference for positive (η2=0.14)
& negative (η2=12) stimuli
Figs 2 & 3. From Rich et al, 2010: effect of
emotional distracters on reaction time and effect
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of positive/negative images, respectively
Neural mechanisms

Brain structure abnormalities: Adleman et al, 2012



Looking at the difference in gray matter volume using VBM
Differences were found in BD compared to HC & SMD [inc GM in
globus pallidus, abnormal inc GM over time in SPL/IPL], and in HC
compared to BD & SMD [inc GM in DLPFC, insula], but nothing to
differentiate SMD specifically
Neural pathways using MEG: Rich et al, 2011

SMD reported greater agitation
than BD & HC, & BD/SMD
reported being less happy than
HC, after blocked goal attainment
task (negative feedback)

SMD: increased activation of
ACC & medial frontal gyrus
compared to HC
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Figs 3 & 4. From
Rich et al, 2011:
greater agitation in
SMD and BD/SMD
more unhappy after
negative feedback
Neural mechanisms
Fig 5. From Rich et al, 2011: difference in MEG activation in L ACC after
negative/positive feedback
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Suggested treatment: I

Group therapy

Waxmonsky et al, 2012: specifically for children w/comorbid
ADHD & SMD

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integrates CBT (affect regulation), parent-training intervention
(manage behaviour); 10 wks
Resulted in:
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decrease in clinician-rated mood symptoms (d=0.81) [maintained at FU,
6 wks post-treatment]
decrease in parent ratings of ADHD (d=0.30), ODD (d=0.26), CD
behaviours (d=0.27) [not maintained at FU]
decrease in impairment (d=2.17), but not fully maintained at FU
Lithium: Dickstein et al, 2009

not found to have significant clinical/neurometabolic effect
University of Central Florida
Suggested treatment: II

Methylphenidate: Waxmonsky et al, 2008


Varying levels of behaviour modification therapy and
methylphenidate [dosage level varied daily]
SMD (w/ADHD) had improvement in externalizing symptoms:

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
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ADHD symptoms: r=0.44-0.58
ODD symptoms: r=0.51
BUT: unclear if criteria for SMD included mania symptoms
One suggested treatment has been chronotherapy
(Heiler et al, 2011)


To retrain the circadian rhythms via exposure to light
Has been shown to decrease depressive symptoms in MDD, and
to have a positive influence on symptoms in ADHD & BD (part.
inattention & irritability)
University of Central Florida
Controversy

Several studies have raised questions about the
‘pathologizing’ of irritability, and the small amount of
data/evidence supporting SMD/DMDD

Axelson et al, 2011: questions the inclusion of SMD in
DSM-V

primarily citing insufficient scientific support and potential
adverse impact on patient care, research, & public’s perceptiom
of child psychiatry

SMD does not have symptom criteria that are specific to it as a
disorder
University of Central Florida
Inclusion in DSM-V

Axelson et al, 2012: longitudinal assessment of
diagnostic validity of DMDD



DMDD was not associated with current or future or parental
history of mood/anxiety disorders
DMDD had limited diagnostic stability: 50% met criteria at only
one assessment, 29% at two assessment, and 19% at three
assessments [2 yr FU]
DMDD not diagnostically distinct: 96% of DMDD had comorbid
diagnoses of ODD or CD, and 77% were comorbid with ADHD &
ODD/CD


40% of BD were comorbid with ODD/CD; 41% of MDD comorbid
with ODD/CD
Conclusion: concerns about diagnostic utility
University of Central Florida
New model
Family risk
o incl family
history of BD
Δ’ neural
pathways
Psychopharmacology
Emotionalprocessing deficits
o amygdala responses
Symptoms
of ADHD &
ODD
Frustration
Therapeutic/
behavioural
interventions
Other
disorders:
MDD/anxiety
University of Central Florida
Core features
o chronic and persistent
irritability
o temper tantrums
Secondary features
o impaired relationships
with family and peers
o problems in school
Thank you!
Questions?
University of Central Florida
References I
1)
2)
3)
4)
5)
6)
7)
8)
9)
Diagram slide 1: http://www.philly.com/philly/blogs/healthy_kids/What-is-Disruptive-MoodDysregulation-Disorder.html
American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders
(5th ed.). Arlington, VA: American Psychiatric Publishing.
Slide 19: http://neuroscience.nih.gov/lab.asp?Org_ID=457
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. Biol 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. Am J Psychiatry, 170, 173179.
Leibenluft, E., Charney, D. S., Towbin, K. E., Bhangoo, R. K., & Pine, D. S. (2003). Defining
clinical phenotypes of juvenile mania. Am J Psychiatry, 160, 430-437.
Brotman, A. A., Kassem, L., Reising, M. M., Guyer, A. E., Dickstein, D. P., Rich, B. A., …
Leibenluft, E. (2007). Parental diagnosis in youth with narrow phenotype bipolar disorder or
severe mood dysregulation. Am J Psychiatry, 164, 1238-1241.
Stringaris, A., Baroni, A., Haimm, C., Brotman, M., Lowe, C. H., Myers, F., … Leibenluft, E.
(2010). Pediatric bipolar disorder verses severe mood dysregulation: risk for manic epsidoes on
follow- up. J Am Acad Child Adolesc Psychiatry, 49, 397-405.
Dickstein, D. P., Nelson, E. E., McClure, E. B., Grimley, M. E., Knopf, L., Brotman, M. A., …
Leibenluft, E (2007). Cognitive flexibility in phenotypes of pediatric bipolar disorder. J Am Acad
Child Adolesc Psychiatry, 46, 3441-3555.
University of Central Florida
References II
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Rich. B. A., Grimley, M. E., Schmajuk, M., Blair, K. A., Blair, R. J. R., & Leibenluft, E. (2008). Face
emption labeling deficits in children with bipolar disorder and severe mood dysregulation. Dev
Psychopathol, 20, 529-546.
Deveney, C. m>, broman, M. A., Decker, A. M., Pine, D. S., & Leibenluft, E. (2012). Affective
prosody labeling in youths with bipolar disorder or severe mood dysregulation. Journal of Child
Psychology and Psychiatry, 53, 262-270.
Brotman, A., A., Rich, B. A., Guyer, A. E., Lunsford, J. R., Horsey, S. E., Reising, M. M., Thomas,
L. A., … Leibenluft, E. (2010). Amygdala activation during emotion processing of neutral faces in
children with severe mood dysregulation versus ADHD or bipolar disorder. Am J Psychiatry, 167,
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Thomas, L. A., Kim, P., Bones, B. L., Hinton, K. E., Milch, H. S., Reynolds, R. C., … Leibenluft, E.
(2013). Elevated amygdala responses to emotional faces in youths with chronic irritability or
bipolar disorder. NeuroImage: Clinical, 2, 637-645.
Hommer, R. E., Meyer, A., Stoddard, J., Connolly, M. E., Mogg, K. Bradley, B. P., … Brotman, M.
A. (2013). Attention bias to threat faces in severe mood dysregulation. Depression and Anxiety,
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Rich, B. A., Schmajuk, M. Perez-Edgar, K. E., Fox, N. A., Pine, D. S., & Leibenluft, E. (2007).
Different psychophysiological and behavioural responses elicited by frustration in pediatric bipolar
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Rich, B. A., Brotman, M. A., Dickstein, D. P., Mitchell, D. G. V., Blair, R. J. R., & leibenluft, E.
2010). Deficits in attention to emotional stimuli dinstinguish youth with sevre mood dysregulation
from youth with bipolar disorder. J Abnorm Child Psychol, 38, 695-706.
University of Central Florida
References III
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Adleman, N. E., Fromm, S. J., Razdan, V., Kayser, R., Dickstein, D. P., Brotman, M. A., Pine, D.
S., & Leibenluft, E. (2012). Cross-sectional and longitudinal abnormalities in brain structure in
children with severe mood dysregulation or bipolar disorder. Journal of Child Psychology and
Psychiatry, 53, 1149-1156.
Rich, B. A., Carver, F. W., Holroyd, T., Rosen, H. R., Mendoza, J. K., Cornwell, B. R.,…
Leibenluft, E. (2011). Different neural pathways to negative affect in youth with pediatric bipolar
disorder and severe mood dysregulation. Journal of Psychiatric Research, 45, 1283-1294.
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. J of Att Dis, 17, 527-541.
Dickstein, D. P., Towbin, K. E., Van Der Veen, J. W., Rich, B. P., Brotman, M. A., Knopf, L., …
Leibenluft, E. (2009). Randomized double-blind placebo-controlled trial of lithium in youths with
severe mood dysregulation. Journal of Child and Adolescent Psychopharmacology 19, 61-73.
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 behavioural modification
in children with attention-deficit/hyperactivity disorder and severe mood dysregulation. Journal of
Child and Adolescent Psychopharmacology 18, 573-588.
Heiler, S., Legenbauer, T., Bogen, T., Jensch, T., & Holtmann, M. (2011). Severe mood
dysreulation: in the “light” of circadian functioning. Medical Hypotheses 77, 692-695.
Axelson, D. A., Birmaher, B., Findling, R. L., Fristad, M. A., Kowatch, R. A., Youngstrom, E. A, …
Diler, R. S. (2011). Concerns regarding the inclusion of temper dysregulation disorder with
dysphoria in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition . J Clin
Psychiatry 72, 1257-1262. University of Central Florida
References IV
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Axelson, R., Findling, R. L., Fristad, M.A., Kowatch, R.A., Youngstrom, E.A., Horwitz, S.M, …
Birmaher, B. (2012). Examining the proposed disruptive mood dysregulation disorder diagnosis in
children in the Longitudinal Assessment of Manic Symptoms Study. J Clin Psychiatry 73, 13421350.
Effect size calculator: http://www.uccs.edu/~lbecker/
University of Central Florida

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