IRRITABILITY, PEDIATRIC MOOD DYSREGULATION. Kenneth E. Towbin, M.D. Chief, Clinical Child & Adolescent Psychiatry Emotion & Development Branch

Transcription

1 1 IRRITABILITY, PEDIATRIC BIPOLAR DISORDER & SEVERE MOOD DYSREGULATION Kenneth E. Towbin, M.D. Chief, Clinical Child & Adolescent Psychiatry Emotion & Development Branch NIMH, NIH, DHHS

2 Talk Outline 2 Irritability Pediatric Bipolar Disorder Severe Mood Dysregulation Is chronic irritability a type of Bipolar Disorder in children and adolescents? Treatment Implications Assessment Tips and Guidelines

3 Irritability 3 No official definition Common Developmental considerations A continuum from ordinary to pathological A symptom or mentioned as a part of many child psychiatric disorders Mood disorders Anxiety Disruptive disorders (ADHD, ODD, CD)

4 How Common is Irritability? 4 Overall prevalence of irritability is not known Surrogate measures ODD (Nock et al NCS-R, JCPP 2007)(3200 adults) lifetime prevalence = 10.2%: (m=11.2%; f=9.2%) 92.4% have another DSM-IV disorder: mood (45.8%), anxiety (62.3%), impulse control (68.2%), subst use (47.2%) LAMS Study (Horowitz et al 2010) (2,220 children) 43% of children presenting for psychiatric clinic care

5 A Definition: Two-Component Model 5 For our work irritability has two components Overall has to be impairing Both components have to be present Consistent Component (uniformly present) A consistent state of grumpy, annoyed, negative mood Event Component Flashes of anger or explosiveness, verbal and/or physical, that are excessive responses to requests or events Consistent + Events = Overall Irritability

6 Measuring the Consistent Component 6 Mood between outbursts Mood (sad, angry) Quality (touchy, annoyed, grouchy) Intensity (mild/variable presence continuous, severe) Problems it creates for the person/those around him Dimensions i Annoyed, grumpy, cranky easily angers often loses temper is often angry gyand resentful is often touchy or easily annoyed by others

7 Measuring the Event Component 7 Measureable features of the event component Frequency Duration Intensity Settings Precipitating factors Perpetuating factors

8 8 DIAGNOSES AND DISORDERS: PEDIATRIC BIPOLAR DISORDER SEVERE MOOD DYSREGULATION

9 What Is a diagnosis? 9 A Diagnosis is a concept, or a hypothesis, about patterns of symptoms Diagnoses propose that specific symptoms (such as behaviors or thoughts/feelings that occur in the mind) belong together or form a meaningful pattern Diagnoses inform us about the course, treatment, and risk factors for a patient

10 10 Increasing Rate of Office Visits Related to Bipolar Disorder (Moreno et al, 2007)

11 Controversies in Dx ing Pediatric BD 11 Bipolar Disorder is characterized by episodes Modification of this idea for children: children with bipolar disorder do not have identifiable episodes Their presentation chronic (i.e., non-episodic)? Is making this modification correct? Should we apply different criteria to children than pp y adults?

12 DSM-IV Sx Criteria for Manic Episode 12 A. Distinct period of elevated, expansive, or irritable mood 1 week B. 3 of the following Sx [or 4, if only irritable] (1) inflated self-esteem, grandiosity (2) decreased need for sleep (3) pressured speech (4) flight of ideas, racing thoughts (5) distractability (6) increased goal-directed activity, psychomotor agitation (7) excessive pleasurable activities with potential for painful consequences

13 Manic Episode requires impairment 13 Mania causes impairment: Marked impairment hospitalization or psychotic features

14 14 THE PROBLEM OF OVERLAPPING SYMPTOMS El E d d l d h Eliminating Episodes and including chronic Irritability: The problem of ADHD

15 DSM-IV Criteria for ADHD 15 Inattention Inattentive to details/makes careless mistakes Has trouble keeping attention on tasks/play Does not seem to listen when spoken to Does not follow instructions, fails to finish things. Has trouble organizing activities. Avoids, dislikes, or doesn't want to do things that take mental effort Loses things needed for tasks/activities Is easily distracted. Is forgetful in daily activities.

16 DSM-IV Criteria for ADHD: II 16 Hyperactivity Often fidgets or squirms in seat Often gets up from seat Often runs about or climbs Often has trouble playing quietly. Is "on the go" or acts as if "driven by a motor" Often talks excessively Impulsivity Blurts out answers before questions have finished Blurts out answers before questions have finished Has trouble waiting his/her turn. Interrupts or intrudes on others

17 ADHD Qualifiers 17 Some symptoms that cause impairment were present before age 7 years. Some impairment from the Sx present in two or more settings Clear evidence of significant impairment in social, Clear evidence of significant impairment in social, school functioning

18 Overlapping Symptoms Across Diagnoses 18 ADHD Bipolar Often fidgets or squirms in seat Often gets up from seat Often runs about or climbs Is "on the go" or acts as if "driven by a motor" Psychomotor agitation Has trouble keeping attention ti on tasks/play Does not seem to listen when spoken to Flight of Ideas

19 Overlapping Symptoms Across Diagnoses 19 ADHD Bipolar Has trouble organizing activities Loses things needed for tasks/activities Is easily distracted. Distractibility Is forgetful in daily activities. Inattention to details makes careless mistakes Has trouble keeping attention on tasks Often talks excessively Excessive, pleasurable activities with potential for painful consequences Pressured Speech

20 Sleep in ADHD (Cortese( et al JAACAP 2009) ) 20 Meta-analysis a a s of 16 studies: Subjectively: Children with ADHD had significantly higher bedtime resistance, more sleep onset difficulties, night awakenings, difficulties with morning awakenings compared with the controls Objectively: children with ADHD had sleep onset latency (on actigraphy), the number of stage shifts/hour sleep, significantly lower sleep efficiency on polysomnography, true sleep time on actigraphy, and average times to fall asleep than the controls

21 DSM-IV Criteria for Mania: Overlap with ADHD 21 A. Distinct i period of elevated, expansive, or irritable i mood 1 week B. Symptoms (1) inflated self-esteem, grandiosity (2) decreased need for sleep (3) pressured speech (4) flight of ideas, racing thoughts (5) distractibilityibili Irritability Symptoms like ADHD (6) increased goal-directed activity, psychomotor agitation (7) excessive,,pleasurable activities with potential for painful consequences

22 Clinical phenotypes of pediatric mania 22 Narrow: > 1 full-duration episode (hypo)mania, with elation Intermediate: Episodes too short Irritability, no euphoria Broad: Severe mood dysregulation (SMD) Chronic Irritable ADHD-like sx s Impairing Leibenluft et al, 2003

23 Goals in Designing Criteria for Severe Mood Dysregulation (SMD) 23 Presentation must be non-episodic. Operationalize irritability clearly Ensure that the irritability is impairing: Appears in 2 settings SMD children should be as impaired as BD Children should have ADHD symptoms that overlap with B mania criteria

24 Dx Criteria for SMD 24 Anger, sadness, irritability that is Present most of the day, most days Evident to those around the child (in more that one setting) Hyperarousal symptoms ( 3 of 6) Insomnia, agitation, i distractibility, ibili racing thoughts, h flight of ideas, pressured speech, intrusiveness Excessive reactivity 3 episodes per week Present for at least 12 months

25 Clinical Picture of SMD 25 A 10 yr old boy is angry all the time ; argues constantly; aggression to property (walls, doors, household items); police called 3 times last year; hits parents. Bossy with peers, few friends, fights w peers at school Enters on high doses of stimulant plus 2 atypical antipsychotic drugs, plus 2 alpha adrenergic drugs First mental health contact at age 3; one 3-wk hospital stay at 9 yrs old 9 medications tried in the past Dx: ADHD, Anxiety Disorder, Mood Disorder

26 Clinical Picture of Bipolar Disorder 26 Unmedicated teenage boy has one week with decreased need for sleep, revelations that he is writing 3 novels at once, writes to colleges saying he should be admitted to teach them his advanced math, has auditory hallucinations in which he hears rumors of the past. Unmedicated teenage girl has 4-days when she had 3 hrs sleep/night, awake painting and drawing, feeling so happy it was scary, like being high, was talking so fast her mother couldn t understand her, highly restless, reported having too many thoughts at once.

27 Is SMD the same as Bipolar Disorder? 27 Data relevant to the question: Longitudinal course (epidemiological studies) Family history Pathophysiological studies And if it s not.what is it? Some similarities might be expected so that bipolar might be more dimensional than just present/absent

28 LONGITUDINAL COURSE 28

29 Two Longitudinal Studies 29 Great Smokey Mountain Study (Brotman et al 2006) 1,420 children assessed at 9, 11, 13, 18 yrs old Interviewers assessed presence of symptoms, not just Dx Most common official diagnosis in those with proxy SMD: Anxiety disorders, disruptive disorders (ODD, ADHD, CD) 32% had no official diagnosis (didn t meet full criteria) Prevalence of SMD in the children was 3.2% Children in the Community Study (Leibenluft et al 2006; Children in the Community Study (Leibenluft et al 2006; Stringaris, et. al 2010) 776 children seen at 13.8, 22, 30 years old Comparison of chronic versus episodic irritability

30 Outcome Data 30 Accumulated data suggest Depression is the most likely outcome Great Smokey Mountain Study The only condition predicted by SMD was major depression SMD was a better predictor of Major Depression than depression in childhood No cases of bipolar disorder Children in the community Only Depression, Dysthymic disorder, Anxiety Disorder predicted by chronic irritability in childhood.

31 Longitudinal follow-up of BD vs. SMD (median=28.4 months) 31 Children with SMD did not develop BD Stringaris et al, 2010

32 Association of Irritability and MDD 32 Increased risk for adult MDD in adolescents with CD: OR=2.20 ( ) (Pine et al, 1998) Increased risk for MDD at age 18 when ODD present at age 7: OR=1.06 ( ) (Burke et al, 2005) Familial association between MDD and disruptive bh behavior disorders d (Weissman et al, 2005) Oppositional Defiant Disorder has two dimensions Headstrong predicts to conduct disorder Irritable predicts to unipolar depression and anxiety disorders

33 A note on Behavioral Disorders 33 Behavioral disorders are not so pure There is large component that mood plays in these conditions Attention to that mood component could be critical to treating them The mood component may be important for the overall outcome

34 Conclusions on Course of Illness in SMD 34 SMD is very common.about 3.2% Chronic irritability predicts Depression Severe irritability is not necessarily diagnostic of Severe irritability is not necessarily diagnostic of mania

35 FAMILY HISTORY 35

36 Rates of BD In Parents of BD vs Parents 36 of SMD Children 40 Brotman et al., % BD BD (n=33) SMD (n=30) OR 17.96, CI , p<.01; Chi-square= 6.32

37 37 BIOLOGICAL/PHYSIOLOGICAL FEATURES

38 38 Task Example: Affective Posner

39 Posner Paradigm: Feedback 39 TASK 1: Baseline TASK 2: Contingency TASK 3: Contingency & Frustration

40 Affective Posner: Subjective Frustration p=.03 p=.03 BD (N= 35) Controls (N=26) SMD (N= 21) Rich et al, 2007

41 Executive Attention (P3 ERP Amplitude at Pz) 41 P3 amplitude at Pz Control (N=26) BD (N=41) SMD (N=23) 8 uv 6 4 * * 2 0 Task 1 Baseline Task 2 Win/Lose $ Task 3 Rigged Significant group x task interaction F(4,112) = 2.67, p=.04 Task 3: BPDs < controls (p=.029); BPDs < SMD Rich (p=.04) et al, 2007

42 Orienting Attention (N1 ERP) in SMD versus BP 42 Control (N=26) SMD (N=21) BPD (N=35) 8 * 6 * * uv 4 2 * * 0 N1 Frontal N1 Central N1 Temporal SMD have problems with initial attention orienting response * p<.05 Rich et al, 2007

43 Structural MRI and Functional MRI 43 No harmful radiation, no needles/injections

44 Face-Emotion Labeling Tasks 44 How hostile is this face? How afraid are you of this face? How wide is the nose?

45 Amygdala Activation: Differences in 45 Diagnostic Groups

46 46 How afraid are you? vs. How wide is nose? Left amygdala ROI, Neutral faces % sig gnal chan nge * * HC (37) ADHD (18) BD (43) SMD (29) Brotman et al, 2010

47 Other fmri Paradigms that show differences between SMD & BP 47 Gender Identification of neutral, angry, fearful faces Probablistic Response Reversal Motor Inhibition (stop signal paradigm) Response flexibility (change paradigm)

48 Overall Summary of SMD and BD 48 Its all about episodes Data indicate that severely, chronically irritable children with ADHD differ from those with BD in Outcome family history brain mechanisms

49 IMPLICATIONS AND TIPS 49

50 Facts 50 There are many disorders that display irritability Irritability doesn t mean just one thing The presence of severe irritability does not necessarily mean a child has bipolar disorder Irritability is: Common Not easy to describe Poorly understood; not studied very much

51 Implications: Treatment 51 If SMD was the same as BD one would consider: Mood stablizers (e. g. anticonvulsant drugs or lithium) Antipsychotics (e.g. risperidone, aripiprazole, quetiapine) BUT if SMD is more like ADHD plus anxiety or plus depression then one ought to consider: stimulants (e.g. methylphenidate, dextroamphetamine) treatments for anxiety or depression such as SSRIs or CBT psychotherapy, or their combination

52 Implications: Treatment II 52 There is a lot we do not know about treatment of Irritability and SMD But we can study treatments now that we can define what we mean by SMD Testable ideas Li was not helpful in SMD Environmental interventions were helpful but Study of benefit of stimulant plus SSRI for SMD is underway

53 Things to watch for and consider 53 Two parts to irritability Mood between outbursts (Consistent component) Outbursts (Event Component) Frequency & duration of outbursts Setting or situations when outbursts occur Home, school, peers Triggers Coping strategies Influenced by development

54 Assessment tips: For SMD or BD 54 Offer examples from direct observation Interview : Parent & child separately Parent & child together Look at effects across different settings

55 Assessment Tips: Bipolar Disorder 55 Are there episodes that are clearly different from usual functioning, or is there a steady presence of disturbed mood? In an episode, symptoms change/occur in a bundle with other symptoms, not in isolation Be cautious about changes associated with medication

56 Assessment Tips: Bipolar Disorder 56 Elevated mood, grandiosity can be tricky Developmental considerations are key Cultural ua cosdea considerations os are ae important For example: the ambiguity of statements like He acts as if the rules don t apply to him. Decreased need for sleep insomnia ADHD and other co-morbid disorders should diagnosed based on symptoms that are present during euthymic period

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