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 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.

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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.

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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.

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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.

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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