Disruptive Mood Dysregulation Disorder (DMDD) Chelsea Wiener

Part 1 DMDD and the DSM V

DMDD Diagnostic Criteria: DSM V Severe recurrent temper outbursts (verbal or behavioral aggression) “grossly out of proportion in intensity or duration” Temper outbursts inconsistent with development level Outbursts occur average of 3+ times/week Mood in-between outbursts is irritably or angry most of the day, nearly every day A-D present 12+ months. No 3+ month period without all of the symptoms 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 Risk For: Temperament DMDD Secondary Features: Chronic irritability Risk For: Depression, anxiety, suicidality, severe aggression, dangerous behavior, psychiatric hospitalization Temperament Symptoms for: ODD, ADHD, anxiety, MDD DMDD Familial anxiety, depression, substance use Secondary Features: Problematic relations with others (peers, family), poor performance in school, low frustration tolerance, dangerous behaviors, suicidality Genetic/Physiological Primary Features: severe, chronic irritability temper tantrums Face emotion labeling differences Attention/cognition differences

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) Increased over 40x from 1993-2003 High comorbidity rates

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 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 Elevated mood, grandiosity/inflated self-esteem, decreased need for sleep (episodic) Symptoms occur in distinct periods (>4 days) Schizophrenia, schizophreniform disorder, schizoaffective illness, pervasive developmental disorder, PTSD, substance abuse in past 3 months IQ<80 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 3258 participants: 2-17 yrs old Child and Adolescent Psychiatric Assessment; Preschool Age Psychiatric Assessment Taken from duke preschool anxiety study, great smoky mountains study, caring for children in the community Criteria present if parent or child endorsed *remember, can’t actually diagnose before age 6

DMDD Prevalence and 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 Odds ratio example explanation: someone with DMDD is 9.9-23.5x more likely to have depression than someone without dmdd

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 462 6 yr old children; parent report structured clinical interview Community sample (no significant medical or develop disabil) Interview 1 used: Preschool Age Psychiatric Assessment

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 Predictors assessed from Yr. 3 Peer functioning: social competence- ratings of children’s behaviors scale popularity: teacher’s estimation of child’s peer status NEI: affect intensity scale

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 Child psychiatric outpatient population (range of manic symptoms) DSM IV measures intake and 2 yr follow up for manic symptoms Used version of Schedule for Affective Disorders and Schizophrenia for School Age Children items to do retro analysis All had initial psychiatric assessment

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 Irritable/mood symptoms 3-4x/week Excessive reactivity 3-4x/week Excluded for mania hypomania etc. GSMS- 25% of highest scorers on externalizing CBCL and then 1/10 sample of those below that

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 31 NP BD (have had manic or hypomanic episode), 31 SMD, 36 NC Kiddie Schedule for Affective Disorders- Present and Lifetime Version, and supplementary SMD model Confound! SMD lower on IQ! And younger. Means not reported, comparisons controlled for this

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 Effect sizes??? Girls in BD group better than boys in BD group; same for NC LIFE= longitudinal interval follow-up evaluation: for family function, open ended questions and clinicians assess on 1-5 scale e.g. family relations, chores, rules, arguments, problem solving SRS=social responsiveness scale; open ended questions about social awareness, social info processing etc.

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) Diagnostic Analysis of Nonverbal Accuracy Child and Adult Facial Expressions subtest faces shown up for 2 seconds 24 faces adult, 24 child

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 Kiddie-schedule for affective disorders- present and lifetime version Shark, puppies, fork etc. Meas. On 1-9 scale

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 SMD younger and lower IQ than BD and control; controlled for this in analyses (interesting to look at separately) Effect sizes: npartial2=.26 for controls to have sig effect of picture emotion; .17 for BD BD and SMD lower accuracy than control (anocova main effect of group npartial2=.12)

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) Post hoc group differences for pos n partial2 .14 and negative .12 Impaired peer relationships measured by LIFE Social reciprocity by SRS Greater RT interference score to negative stimuli with increased age r=.55

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 Neutral because in past research BP children have rated as more hostile and fear producing, and related to amygdala hyperactivity Medication free for testing (ADHD at least 48 hrs)

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 SMD younger than BP covary out age Effect size?? No differences in right amygdala Emphasize ADHD vs. SMD contrast- large comorbidity, but ADHD doesn’t have the irritability Included pos and neg faces b/c other comparisons affect neutral interpretation Most BP and SMD were medicated

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 57 participants No medication confounds Male and female faces

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 BOLD- blood oxygenation level-dependent No right amygdala differences

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 Processing positive stimuli for SMD Can’t find any effect sizes reported

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) Effect sizes not reported Greater self reports of frustration in general associated with reduced activation during negative feedback trials:

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 Authors surprised about amygdala hypoactivation

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 MEG recording/MRI

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): 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 Effect sizes not reported “SMD experience heightened frustration in emotional context”

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 70% SMD comorbid with ADHD

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 Category naming test (CNT) Producing words, attention, set shifting ADHD- combined Controlled oral word association test- produce as many words starting with a specific letter CNT- produce as many animal names as possible Study conducted in Turkey

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 But a lot of SMD ADHD lifetime comorbidity (62.5% of SMD group met lifetime ADHD) Connor’s Parent Rating Scale-Revised Long Form, Conner's’ Teacher Rating Scale-Revised Long Form

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 Amydala=decision making and emotional reactions and aggression

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 Lithium affects Affects myoinositol (mI), which is often increased in BD adults Participants recruited from psychiatrists, advertisements in parent magazines, support groups online Stayed inpatient for duration

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 No difference between people who were randomized or not randomized PANSS and CGI not a lot of improvement for anyone

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 Risperidone b/c has been shown to be helpful in reducing rage and irritability in other populations (also used schizophrenia and BP- reduce psychotic symptoms) Mean IQ 93 SD 9 .5 3 mg dosage

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) ES compared to baseline

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 Conditions: 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 No manic activation! Effect sizes not reported

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: 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 reduce- 2 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 ADHD combined type Parent components: COPE and MFPG; child Summer Treatment Program, Coping Power Program, Fristad’s MFPG

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 YMRS: elevated mood, increased motor activity, sexual interest, sleep, irritability, language-thought disorder, content, disruptive aggressive behavior, appearance, insight

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 Emotion Processing Differences Treatment Behavior modification Differences in: *amygdala activation ACC, MFG, SFG, Insula, Striatal Genetic/Physiological DMDD/ SMD Risk for: mood disorders Primary characteristic: chronic irritability Secondary Characteristics: ODD behaviors ADHD behaviors hyperarousal Temperament Agitation, irritability, low frustration tolerance Hostility, lifetime substance use Parent Factors

Vs. DSM V Schematic Risk For: Temperament DMDD Secondary Features: Chronic irritability Risk For: Depression, anxiety, suicidality, severe aggression, dangerous behavior, psychiatric hospitalization Temperament Symptoms for: ODD, ADHD, anxiety, MDD DMDD Familial anxiety, depression, substance use Secondary Features: Problematic relations with others (peers, family), poor performance in school, low frustration tolerance, dangerous behaviors, suicidality Genetic/Physiological Primary Features: severe, chronic irritability temper tantrums Face emotion labeling differences Attention/cognition differences

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