Assessment and Management of Severe Irritability from ...€¦ · DMDD criteria DMDD cannotcoexist with ODD Intermittent Explosive Disorder Bipolar Disorder Can coexist with MDD ADHD

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Assessment and Management of Severe Irritability from Preschool to High School

Assessment and Management of Severe Irritability from Preschool to High School

Jeffrey Hunt, MDJeffrey Hunt, MD

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Disclosure StatementsDisclosure StatementsSheppard Pratt holds the standard that its continuing medical education programs should be free of commercial bias and conflict of interest. In accord with Sheppard Pratt's Disclosure Policy, as well as standards of the Accreditation Council for Continuing Medical Education (ACCME) and the American Medical Association (AMA), all planners, reviewers, speakers and persons in control of content have been asked to disclose any relationship he /she (or a partner or spouse) has with any entity producing, marketing, re-selling, or distributing health care goods or services consumed by, or used on, patients, during the past 12 months. All planners, reviewers and speakers have also been asked to disclose any payments accepted for this lecture from any entity besides Sheppard Pratt Health System, and if there will be discussion of any products, services or off-label uses of product(s) during this presentation.

Jeffrey I. Hunt, MD reports having no financial interest, arrangement or affiliation with any entity producing, marketing, re-selling, or distributing health care goods or services consumed by, or used on, patients, during the past 12 months. He will discuss SSRIs and atypicals, medications used for treating irritability in youth in this presentation.

Event Planners/Reviewers Disclosures: The following event planners and/or reviewers are reported as having no financial interest, arrangement or affiliation with any entity producing, marketing, re-selling, or distributing health care goods or services consumed by, or used on, patients, during the past 12 months: Todd Peters, M.D., Briana Riemer, M.D., Sunil Khushalani, M.D., Faith Dickerson, Ph.D., Carrie Etheridge, LCSW-C, Tom Flis, LCPC, Laura Webb, RN-BC, MSN, Stacey Garnett, RN, MSN, Paul Daugherty, RN, MBA, Heather Billings, RN, and Jennifer Tornabene.

Sheppard Pratt holds the standard that its continuing medical education programs should be free of commercial bias and conflict of interest. In accord with Sheppard Pratt's Disclosure Policy, as well as standards of the Accreditation Council for Continuing Medical Education (ACCME) and the American Medical Association (AMA), all planners, reviewers, speakers and persons in control of content have been asked to disclose any relationship he /she (or a partner or spouse) has with any entity producing, marketing, re-selling, or distributing health care goods or services consumed by, or used on, patients, during the past 12 months. All planners, reviewers and speakers have also been asked to disclose any payments accepted for this lecture from any entity besides Sheppard Pratt Health System, and if there will be discussion of any products, services or off-label uses of product(s) during this presentation.

Jeffrey I. Hunt, MD reports having no financial interest, arrangement or affiliation with any entity producing, marketing, re-selling, or distributing health care goods or services consumed by, or used on, patients, during the past 12 months. He will discuss SSRIs and atypicals, medications used for treating irritability in youth in this presentation.

Event Planners/Reviewers Disclosures: The following event planners and/or reviewers are reported as having no financial interest, arrangement or affiliation with any entity producing, marketing, re-selling, or distributing health care goods or services consumed by, or used on, patients, during the past 12 months: Todd Peters, M.D., Briana Riemer, M.D., Sunil Khushalani, M.D., Faith Dickerson, Ph.D., Carrie Etheridge, LCSW-C, Tom Flis, LCPC, Laura Webb, RN-BC, MSN, Stacey Garnett, RN, MSN, Paul Daugherty, RN, MBA, Heather Billings, RN, and Jennifer Tornabene.

Disclosures of Potential Conflicts:Disclosures of Potential Conflicts:

Source Research Funding

Advisor/Consultant

Employee Speaker’s Bureau

Books, IntellectualProperty,

In-kind Services (e.g.,travel)

Stock orEquity

Honorarium or expenses for this presentation or meeting

NIMH LifespanPhysicians Group

Wiley Publishers

Yes

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Physician Statement: Sheppard Pratt is accredited by The Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. Sheppard Pratt takes responsibility for the content, quality, and scientific integrity of this CME activity. Sheppard Pratt designates this live activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Nurse Statement: Sheppard Pratt is an approved provider of continuing nursing education by Maryland Nurses Association, an accredited approver by the American Nurses Credentialing Center’s Commission on Accreditation. Sheppard Pratt takes responsibility for the content, quality, and scientific integrity of this CME activity. This activity is approved for 1.0 contact hours for nurses.

Psychologist Statement: Sheppard Pratt is authorized by the State Board of Examiners of Psychologists as a sponsor of continuing education. Sheppard Pratt takes responsibility for the content, quality, and scientific integrity of this CME activity. Sheppard Pratt designates this educational activity for a maximum of 1.0 CEU hours for Psychologists.

Social Worker Statement: Sheppard Pratt is authorized by the Board of Social Work Examiners of Maryland to offer continuing education for Social Workers. Sheppard Pratt takes responsibility for the content, quality, and scientific integrity of this CME activity. This activity is approved for 1.0 CEU contact hours in Category 1 credits for Social Workers.

Counselor Statement: Sheppard Pratt has been approved by NBCC as an Approved Continuing Education Provider, ACEP No. 5098. Programs that do not qualify for NBCC credit are clearly identified. Sheppard Pratt is solely responsible for all aspects of the program. This activity is available for 1.0 NBCC clock hours.

Learning ObjectivesLearning Objectives

Describe the historical conceptualization of irritability as a symptom in psychiatric disorders

Highlight the differences between episodic vs chronic irritability

Define the criteria for DMDD

Discuss severe irritability in the context of preschool age children

Briefly discuss neuroscience and genetic research trends related to irritability

Describe evidenced-based approaches in managing irritability





Briefly discuss neuroscience and genetic research trends related to irritability


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Case history: JedCase history: Jed

Picture courtesy of www.dbsalliance.org

Jed is a 9 year old male referred for evaluation of 2 year history of nearly daily temper tantrums. He is very easily frustrated and becomes rageful, most often toward mother, when his needs are not met. He has difficultymaking friends and prefers to spend time on video games. Since COVID-19 quarantine began his moodiness has increased. The parents report substantial stress from parenting him. Mom reports “constant walking on egg shells”

PPH: he has a therapist but “hates going.” no medication

SH: only child – mom is teacher; father is engineer – recent treatment for glioblastoma

FH: post partum depression in mom; pat grandmother “I think she had bipolar disorder”

PMH: Healthy

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ObjectivesObjectives





Briefly discuss neuroscience research trends








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Pediatric Bipolar Disorder and Irritability: Primary ControversyPediatric Bipolar Disorder and Irritability: Primary Controversy

The frequent diagnosis of bipolar disorder in children with chronically irritable mood redefined bipolar disorder in early life as a non-episodic syndrome

This diagnostic approach contributed to the dramatic rise in the rate of pediatric visits for bipolar disorder in the United States

Rise in polypharmacy

Rise in use of atypical antipsychotics

Led to introduction of DMDD

The frequent diagnosis of bipolar disorder in children with chronically irritable mood redefined bipolar disorder in early life as a non-episodic syndrome

This diagnostic approach contributed to the dramatic rise in the rate of pediatric visits for bipolar disorder in the United States

Rise in polypharmacy

Rise in use of atypical antipsychotics

Led to introduction of DMDD

Roy, Lopes & Klein 2014, Carlson 2011; Francis 2012

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• Of the 43 children who met criteria for mania

• 77% (n=33) – persistent irritability

• 14% (n=6) – elation

• 9% (n = 4) - full of energy or many thoughts.

– Only 16% (n=7) were episodic (> 1 episodes of mania) remainder were chronic

– This study was very influential - irritability and chronicity as hallmark of BP

• Of the 43 children who met criteria for mania

• 77% (n=33) – persistent irritability

• 14% (n=6) – elation

• 9% (n = 4) - full of energy or many thoughts.

– Only 16% (n=7) were episodic (> 1 episodes of mania) remainder were chronic

– This study was very influential - irritability and chronicity as hallmark of BP

JAACAP 34(7), 1995

Bipolar Disorder: Over diagnosed?Bipolar Disorder: Over diagnosed?

1994-19952002-2003:

Ped BD 40-fold increase!

<19yo 25/100,0001003/100,000

>20yo 905/100,0001679/100,000

National Ambulatory Medical Care Survey (NAMCS) annually by National Center for Health Statistics.

1994-19952002-2003:

Ped BD 40-fold increase!

<19yo 25/100,0001003/100,000

>20yo 905/100,0001679/100,000

National Ambulatory Medical Care Survey (NAMCS) annually by National Center for Health Statistics.

Moreno et al. Arch Gen Psych 2007

DSM-IVPublished

Irritability is Not Specific Irritability is Not Specific

Bipolar disorders

Major depressive episode

Gen. anxiety disorder

PTSD

Oppositional defiant disorder

ADHD

Conduct disorder

Intermit. explosive disorder

Autism spectrum disorders

Bipolar disorders

Major depressive episode

Gen. anxiety disorder

PTSD

Oppositional defiant disorder

ADHD

Conduct disorder

Intermit. explosive disorder

Autism spectrum disorders

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Irritability: TerminologyIrritability: Terminology

Irritability: increased proneness to anger relative to similarly developed

peers

Anger: Consciously perceived

emotion/feeling with irritability

Rage:

Intense anger

Frustration:

Emotional state induced by block goal attainment; Frustrative non-

reward resulting in increased aggression

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Stringaris A. J Child Psychol Psych 59;7 2018 721-739

Kraepelin Description of irritable maniaKraepelin Description of irritable mania

“.…On the other hand there often exists a great emotional irritability. The patient is dissatisfied, intolerant, fault-finding… he becomes pretentious, positive, regardless, impertinent and even rough, when he comes up against opposition to his wishes and inclinations; trifling external occasions may bring about violent outbursts of rage.”

Kraepelin, 1921

Irritability: Long recognized as a problemIrritability: Long recognized as a problem

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Irritability: TerminologyIrritability: Terminology

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Chronic irritability: Worse than peers but not different than child’s baseline (DSM >12 months)

Episodic Irritability: Change from child’s baseline and worse than peers; Found in MDD and BD

Tonic Irritability: Persistent irritable mood in between outbursts (part of DMDD)

Phasic Irritability: Temper outbursts on top of Tonic Irritability

Chronic irritability: Worse than peers but not different than child’s baseline (DSM >12 months)

Episodic Irritability: Change from child’s baseline and worse than peers; Found in MDD and BD

Tonic Irritability: Persistent irritable mood in between outbursts (part of DMDD)

Phasic Irritability: Temper outbursts on top of Tonic Irritability

Stringaris A. J Child Psychol Psych 59;7 2018 721-739

Irritability common in BP and ADHDIrritability common in BP and ADHD

Geller et al., 2002

Irritablity as symptom of Bipolar Disorder across studiesIrritablity as symptom of Bipolar Disorder across studies

Rates of irritability and elation vary significantly across study samples. Rates of irritability and elation vary significantly across study samples.

0

50

100

Findling Wozniak Geller Axelson

elation

irritability

Adapted from Kowatch, et al., 2005

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both

ela on

irritability

75%

15%

10%

Hunt et al, JAACAP, 2009

Hunt et al., JAACAP 2009

Identifying Irritability only subgroup in the COBY Sample Identifying Irritability only subgroup in the COBY Sample

Secondary analysis using KSAD-MRS Category A symptoms to define three groups

361 subjects had both most serious past and current MRS ratings

Looking for between group differences at baseline and longitudinally

Secondary analysis using KSAD-MRS Category A symptoms to define three groups

361 subjects had both most serious past and current MRS ratings

Looking for between group differences at baseline and longitudinally

Hunt et al., JAACAP 2009

K-SADS MRS: IrritabilityK-SADS MRS: Irritability

Subjective feeling of irritability, anger, crankiness, bad temper, short tempered, resentment, or annoyance, externally directed, whether expressed overtly or not.

Rate the intensity and duration of such feelings.

Do not rate here if irritability is due to depression or disruptive disorders.

Subjective feeling of irritability, anger, crankiness, bad temper, short tempered, resentment, or annoyance, externally directed, whether expressed overtly or not.

Rate the intensity and duration of such feelings.

Do not rate here if irritability is due to depression or disruptive disorders.

• Mild: Often feels definitely more angry, irritablethan called for by the situation. relatively frequent but never very intense

• Moderate: Most days irritable/angry or over 50% of awake time.

• Severe: At least most of the time child is aware of feeling very irritable or quite angry or has frequent homicidal thoughts (no plan) or thoughts of hurting others. Or throws and breaks things around the house.

• Extreme: Most of the time feels extremely angry or irritable, to the point s/he "can't stand it." Or frequent uncontrollable tantrums.

• Mild: Often feels definitely more angry, irritablethan called for by the situation. relatively frequent but never very intense

• Moderate: Most days irritable/angry or over 50% of awake time.

• Severe: At least most of the time child is aware of feeling very irritable or quite angry or has frequent homicidal thoughts (no plan) or thoughts of hurting others. Or throws and breaks things around the house.

• Extreme: Most of the time feels extremely angry or irritable, to the point s/he "can't stand it." Or frequent uncontrollable tantrums.

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COBY: Episodic irritable mania existsCOBY: Episodic irritable mania exists

At baseline

Irritable only, elated only, and both elation and irritable groups are phenomenologically similar

At 48 months:

Episodic Irritable BP patients remain similar to subjects with elation with regard to most longitudinal outcomes

Most subjects went on to have both irrit and elation

Irritable only BP patients more frequently subsyndromal and syndromal for depression

At baseline

Irritable only, elated only, and both elation and irritable groups are phenomenologically similar

At 48 months:

Episodic Irritable BP patients remain similar to subjects with elation with regard to most longitudinal outcomes

Most subjects went on to have both irrit and elation

Irritable only BP patients more frequently subsyndromal and syndromal for depression

Hunt et al., 2009; 2013

Episodicity vs. chronicityEpisodicity vs. chronicity

longitudinal studies of irritabilitylongitudinal studies of irritability

1141 households in semirural NY.

time 1 - mean age 13



Different associations with age:

episodic=linear; chronic=curvilinear

Episodic irritability predicts mania

Chronic irritability predicts depression

1141 households in semirural NY.




Different associations with age:

episodic=linear; chronic=curvilinear

Episodic irritability predicts mania

Chronic irritability predicts depression Leibenluft J Child Adolesc Psychopharm 2006

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631 subjects followed from age 13.8 to 33.2 years:

MDD, Dysthymia, and GAD significantly increased at 20 years

Bipolar diagnosis not increased at 20 year follow-up

631 subjects followed from age 13.8 to 33.2 years:

MDD, Dysthymia, and GAD significantly increased at 20 years

Bipolar diagnosis not increased at 20 year follow-up

Stringaris et al., JAACAP 2011

84 youths with SMD and 93 with BP-I followed a median of 28.4 months.

Clinical Phenotypes of Pediatric ManiaClinical Phenotypes of Pediatric Mania

Leibenluft E Am J Psychiatry 2003

Narrow:

full-duration episodes

hallmark symptoms (elevated expansive mood)

Broad:

Severe mood dysregulation

chronic irritability

no hallmark symptoms.

Intermediate (Hypo)mania-NOS: hallmark symptoms but short episodes.

Irritable (Hypo)mania: full duration episodes; NO hallmark symptoms

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SMD: Precursor to DMDDSMD: Precursor to DMDD

Severe Mood Dysregulation•Abnormal mood: anger or sadness

•No symptom-free period exceeding 2 months

•Aged 7 – 17, with symptom onset before age 12

•Symptoms severe in at least 1 setting and mild symptoms in a second setting

•Hyperarousal

DMDD• Irritable mood

•No symptom-free period exceeding 3 months

•Aged 6 – 17, with symptom onset before age 10

•Symptoms must be present in at least 2 of 3 settings

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Disruptive mood dysregulation disorder296.99

Disruptive mood dysregulation disorder296.99

Addresses concerns about potential for over diagnosis of bipolar disorder in children

Placed in Depressive Disorders chapter reflecting longitudinal research that children with this symptom pattern typically develop unipolar depression or anxiety and not bipolar disorder

Addresses concerns about potential for over diagnosis of bipolar disorder in children

Placed in Depressive Disorders chapter reflecting longitudinal research that children with this symptom pattern typically develop unipolar depression or anxiety and not bipolar disorder

DMDD criteriaDMDD criteria

Severe recurrent temper outbursts

Verbally or behaviorally

Grossly out of proportion in intensity and duration to situation

Inconsistent with developmental level

Occur three or more times per week

Mood between temper outbursts is persistently irritable or angry

Observable by others (parents, teachers, peers)

Present for 12 + months

No period longer than 3 months without all symptoms

Present in at least two of three settings

Severe recurrent temper outbursts

Verbally or behaviorally

Grossly out of proportion in intensity and duration to situation

Inconsistent with developmental level

Occur three or more times per week

Mood between temper outbursts is persistently irritable or angry

Observable by others (parents, teachers, peers)

Present for 12 + months

No period longer than 3 months without all symptoms

Present in at least two of three settings

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Not made before age 6 or after 18

Age of onset (by history or observation) before age 10

Never a distinct period lasting one full day during which full criteria (except duration) for manic symptoms are met

Do not occur exclusively during MDD episode

Also not better explained by ASD, PTSD, SAD, persistent depressive disorder

Not made before age 6 or after 18

Age of onset (by history or observation) before age 10

Never a distinct period lasting one full day during which full criteria (except duration) for manic symptoms are met

Do not occur exclusively during MDD episode

Also not better explained by ASD, PTSD, SAD, persistent depressive disorder


DMDD cannot coexist with

ODD

Intermittent Explosive Disorder

Bipolar Disorder

Can coexist with

MDD

ADHD

CD

SUD

DMDD cannot coexist with

ODD

Intermittent Explosive Disorder

Bipolar Disorder

Can coexist with

MDD

ADHD

CD

SUD

DMDD trumps ODD DMDD trumps ODD

DMDDDMDD

Duration: 12+ months

Age: 6 to 18 y.o.

Frequency: temper outbursts ≥ 3 x wk

Mood: persistently angry most of the day nearly every day

Verbal and behavioral temper outbursts

Duration: 12+ months

Age: 6 to 18 y.o.

Frequency: temper outbursts ≥ 3 x wk

Mood: persistently angry most of the day nearly every day

Verbal and behavioral temper outbursts

ODD ODD

Duration: 6+ months

Age: < 18 y.o.

Frequency:

< 5 y.o.: most days

> 5 y.o.: 1 x week

Spiteful or vindictive at least twice in last 6 mos.

Mood: often angry and resentful

Verbal outbursts

Duration: 6+ months

Age: < 18 y.o.

Frequency:

< 5 y.o.: most days

> 5 y.o.: 1 x week

Spiteful or vindictive at least twice in last 6 mos.

Mood: often angry and resentful

Verbal outbursts

If meet criteria for both, DMDD is the diagnosis

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DMDD vs BP BP Symptoms are episodic and are above and beyond childs other psychiatric disorders

DMDD vs BP BP Symptoms are episodic and are above and beyond childs other psychiatric disorders

DMDD, ADHD or ODD

For example:

Bipolar symptoms

DMDD: Field TrialsDMDD: Field Trials

• Variable Kappa found between sites

• More reliable in inpatient settings for more severe patients

• Variable Kappa found between sites

• More reliable in inpatient settings for more severe patients

35Am J Psychiatry 2013; 170:59–70

DMDD: Trial RunDMDD: Trial Run

• Used existing data from 3 large epidemiological samples

• Covered a broad age range:

• Preschool (ages 2 – 5 years)

• School-age through adolescence (ages 9 – 17 years)

• Used existing data from 3 large epidemiological samples

• Covered a broad age range:

• Preschool (ages 2 – 5 years)

• School-age through adolescence (ages 9 – 17 years)

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Am J Psychiatry 170:2, February 2013

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DMDD: Trial RunDMDD: Trial Run

• Nearly ½ of school-age youths were reported to have severe temper outbursts during the 3 months prior to assessment:

• Applying the duration criteria dropped the prevalence to 1.5% –2.8%

• Applying all the DMDD criteria resulted in a prevalence of about 1%

• Nearly ½ of school-age youths were reported to have severe temper outbursts during the 3 months prior to assessment:

• Applying the duration criteria dropped the prevalence to 1.5% –2.8%

• Applying all the DMDD criteria resulted in a prevalence of about 1%

• 3.3% of preschoolers had DMDD

• Prevalence highly dependent upon applying criteria:

• Frequency

• Intensity

• Persistence

• Retrospective recall problematic

• 3.3% of preschoolers had DMDD

• Prevalence highly dependent upon applying criteria:

• Frequency

• Intensity

• Persistence

• Retrospective recall problematic

37Copeland et al., Am J Psychiatry 170:2, February 2013;

DMDD: Summary of Prevalence DMDD: Summary of Prevalence

38Copeland et al., Am J Psychiatry 170:2, February 2013;

3.3 % 1.1 % 0.8 %

DMDD: Adult Outcomes DMDD: Adult Outcomes

The long-term prognosis of children with DMDD is one of pervasive impaired functioning that in many cases is worse than that of other childhood psychiatric disorders

The long-term prognosis of children with DMDD is one of pervasive impaired functioning that in many cases is worse than that of other childhood psychiatric disorders

39Copeland et al., Am J Psychiatry 2014

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Can DMDD be identified in early childhood? Can DMDD be identified in early childhood?

• Core DMDD symptoms (e.g. recurrent temper loss and persistent irritability) are common presenting concerns for some preschoolers

• Core DMDD symptoms (e.g. recurrent temper loss and persistent irritability) are common presenting concerns for some preschoolers

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• Examined DMDD symptoms in preschool-aged children (4 – 5 years)

• Frequency

• Behavioral impairment

• Comorbidity

• Family functioning

• Examined DMDD symptoms in preschool-aged children (4 – 5 years)

• Frequency

• Behavioral impairment

• Comorbidity

• Family functioning

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PPHP: Irritability in Young ChildrenPPHP: Irritability in Young Children

• Participants: 139 children

• Ages 4-0 to 5-11 years

• 75% male

• Median yearly income = $40,000

• Participants: 139 children

• Ages 4-0 to 5-11 years

• 75% male

• Median yearly income = $40,000

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PPHP: Irritability in Young ChildrenPPHP: Irritability in Young Children

• Diagnostic Infant and Preschool Assessment (DIPA):

• Modified diagnostic criteria for DMDD

• Frequent temper loss (e.g. tantrums, screaming, hitting / throwing things) → ODD module

• Temper outbursts at least 3x weekly

• Persistently irritable / angry mood at least 5x weekly → MDD module

• Duration of irritability of at least 12 months → MDD module

• Diagnostic Infant and Preschool Assessment (DIPA):

• Modified diagnostic criteria for DMDD

• Frequent temper loss (e.g. tantrums, screaming, hitting / throwing things) → ODD module

• Temper outbursts at least 3x weekly

• Persistently irritable / angry mood at least 5x weekly → MDD module

• Duration of irritability of at least 12 months → MDD module

• Child Behavior Functioning

• Child Behavior Checklist (CBCL 1 ½ - 5)

• Peabody Picture Vocabulary Test

• Family Functioning and Psychiatric History

• Parenting Stress Index

• Family History Screening

• Center for Epidemiological Studies Depression Scale

• Child Behavior Functioning

• Child Behavior Checklist (CBCL 1 ½ - 5)

• Peabody Picture Vocabulary Test

• Family Functioning and Psychiatric History

• Parenting Stress Index

• Family History Screening

• Center for Epidemiological Studies Depression Scale

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PPHP: Frequency of DMDD symptomsPPHP: Frequency of DMDD symptoms

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Criteria N (%)

(A &B)Severe temper – inconsistent w developmental level

128 (92%)

(C)Temper 3+ times per week

118 (85%)

(D)Persistent irritability – 5+ days/week

94 (68%)

(E)Duration at least 12 months

77 (55%)

(A-E)Meets all criteria

63 (45%)

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PPHP: DMDD symptoms in preschoolersPPHP: DMDD symptoms in preschoolers

Comorbidity in DMDD+ preschoolers:

• 63 children met criteria for DMDD

• 52 (82.5%) also met criteria for ODD

• 38 (60.3%) of these children also met criteria for ADHD

• 7 (11.1%) met criteria for DMDD alone

Comorbidity in DMDD+ preschoolers:

• 63 children met criteria for DMDD

• 52 (82.5%) also met criteria for ODD

• 38 (60.3%) of these children also met criteria for ADHD

• 7 (11.1%) met criteria for DMDD alone

46

38

14

4

7

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

DMDD + ODD + ADHD DMDD + ODD (No ADHD)

DMDD + ADHD (No ODD) DMDD Only

DMDD symptoms are associated with:DMDD symptoms are associated with:

47

High levels of child aggression and reactivity

Decreased receptive language skills

Increased parental stress

High rates of co-occurrence with ODD and ADHD

High levels of child aggression and reactivity

Decreased receptive language skills

Increased parental stress

High rates of co-occurrence with ODD and ADHD

Irritability in Young ChildrenIrritability in Young Children

48

Next steps?

• Affective Reactivity Index (ARI)

• Parent report

• Milieu staff report

• Piloting ARI self-report interviews in preschool-age children

Next steps?

• Affective Reactivity Index (ARI)

• Parent report

• Milieu staff report

• Piloting ARI self-report interviews in preschool-age children

17






Briefly discuss neuroscience and genetics research trends






Briefly discuss neuroscience and genetics research trends


49

Irritability: MechanismsIrritability: Mechanisms

Frustrative Non-Reward

• Normal emotional state but when unable to achieve a goal:

• Increased aggression and activity

• Decreased striatal activity

• Decreased frontal cortex activation in irritable youths

Frustrative Non-Reward

• Normal emotional state but when unable to achieve a goal:

• Increased aggression and activity

• Decreased striatal activity

• Decreased frontal cortex activation in irritable youths

Threat

• Situation or object signals harm:

• Fight or flight

• Increased vigilance to threatening stimuli:

• Angry faces

• Misinterprets neutral faces

• Difficulty modulating amygdala

Threat

• Situation or object signals harm:

• Fight or flight

• Increased vigilance to threatening stimuli:

• Angry faces

• Misinterprets neutral faces

• Difficulty modulating amygdala

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Research: NeurocircuitryResearch: Neurocircuitry

51

Leibenluft, Trends in Cognitive Sciences,April 2017,

18

Research: Frustrative non-reward Research: Frustrative non-reward

Youth with SMD showed decreased amygdala activity when receiving frustrating, negative feedback

Youth with SMD showed decreased amygdala activity when receiving frustrating, negative feedback

52Leibenluft, Trends in Cognitive Sciences, April 2017

Research: Aberrant response to threatResearch: Aberrant response to threat

53

Associations between aberrant responses to threat and irritability

Irritability in youth is associated with aberrant amygdala-prefrontal cortex connectivity when viewing threatening faces

Associations between aberrant responses to threat and irritability

Irritability in youth is associated with aberrant amygdala-prefrontal cortex connectivity when viewing threatening faces

Leibenluft, Trends in Cognitive Sciences, April 2017,

• Examined whether there were multiple forms of irritability:

• ”Neurodevelopmental / ADHD-like” subtype → childhood onset

• “Depression / mood” type → onset in adolescence

• Examined whether there were multiple forms of irritability:

• ”Neurodevelopmental / ADHD-like” subtype → childhood onset

• “Depression / mood” type → onset in adolescence

54

Riglin et al., Am J Psychiatry 2019; 176:635–642

19

Irritability: Novel TypesIrritability: Novel Types

• Avon Longitudinal Study of Parents and Children (ALSPAC)

• 7,924 participants

• Irritability assessed using the ODD section of the Development and Well-Being Assessment

• Avon Longitudinal Study of Parents and Children (ALSPAC)

• 7,924 participants

• Irritability assessed using the ODD section of the Development and Well-Being Assessment

Polygenic risk scores (PRSs) for ADHD and MDD risk alleles were identified from Psychiatric Genomics Consortium analysis of case-control GWAS.

Polygenic risk scores (PRSs) for ADHD and MDD risk alleles were identified from Psychiatric Genomics Consortium analysis of case-control GWAS.

55

Irritability: Novel TypesIrritability: Novel Types

• Identified 5 irritability trajectory classes:

• Low

• Decreasing

• Increasing

• Late-childhood limited

• High-persistent

• Identified 5 irritability trajectory classes:

• Low

• Decreasing

• Increasing

• Late-childhood limited

• High-persistent

56Riglin et al., 2019

Irritability: associated with genetic liabilityIrritability: associated with genetic liability

57

• The developmental context of irritability may be important in its conceptualization: early-onset persistent irritability may be more neurodevelopmental/ADHD-like and later-onset irritability more depression/mood-like.

• These findings may have implications for treatment as well as nosology.

Riglin et al., 2019

20














58

Assessement of Irritability: Assessement of Irritability:

DMDD K-SADS

• Semi-structured interview

Development and Wellbeing Assessment

• DMDD module

• Structured interview

• Online

DMDD K-SADS

• Semi-structured interview

Development and Wellbeing Assessment

• DMDD module

• Structured interview

• Online

• Clinician-rated measures:

• Clinician Global Impression (CGI)

• Clinician Affective Reactivity Index

• Clinician-rated measures:

• Clinician Global Impression (CGI)

• Clinician Affective Reactivity Index

59

Irritability: Questionnaires Irritability: Questionnaires

Affective Reactivity Index (ARI)

• Brief 7-item measure

• Assesses:

• Feelings and behaviors centered around irritability (items 1-6)

• Associated functional impairment

Affective Reactivity Index (ARI)

• Brief 7-item measure

• Assesses:

• Feelings and behaviors centered around irritability (items 1-6)

• Associated functional impairment

60Stringaris, Goodman, et al., 2012

21

Irritability: Questionnaires Irritability: Questionnaires

Multidimensional Assessment of Preschool Disruptive Behavior (MAP-DB) Questionnaire

• Valid instrument to assess irritability in preschool children

• 20-item measure

• Assess features of tantrums and anger regulation

• Covers a broad range of behaviors

Multidimensional Assessment of Preschool Disruptive Behavior (MAP-DB) Questionnaire

• Valid instrument to assess irritability in preschool children

• 20-item measure

• Assess features of tantrums and anger regulation

• Covers a broad range of behaviors

61Wakschlag et al., 2010

Irritability: ManagementIrritability: Management

• Treat comorbid conditions first!

• Can add psychological treatment:

• Cognitive behavioral therapy (CBT)

• Parent management training (PMT)

• Pharmacological treatment should be a last resort

• Treat comorbid conditions first!

• Can add psychological treatment:

• Cognitive behavioral therapy (CBT)

• Parent management training (PMT)

• Pharmacological treatment should be a last resort

62

Irritability: ManagementIrritability: Management

63

Depression

ADHD

ODD / CD

Anxiety

•DMDD co-occurs with another disorder in 65% – 90% of cases

22

Stringaris et al. 2018 Mechanisms of Irritability

Assessment:Parental negativity /warmth

Treatment:Parenting intervention

Treating Irritability in Children: TherapyTreating Irritability in Children: Therapy

• Parent management training (Barkley 1997, 2000)

• Standardized daily routines and social rhythms (Frank 1997)

• Collaborative problem solving used for ODD (Greene 2003, 2004).

• Family therapy (Fristad 2003, Miklowitz 2003, Pavuluri 2004, Keitner 1995)

• DBT for adolescents with mood disorders (Goldstein et al.,2007)

• Interpretation Bias Training (Stoddard et al., 2016)

Treating Irritability in Children: Parent Management TherapyTreating Irritability in Children: Parent Management Therapy

Parent management training (Barkley 1997, 2000)

23

Treating Irritability in Children: Parent Management TherapyTreating Irritability in Children: Parent Management Therapy

http://www.continuingedcourses.net/active/courses/course079.phpParent management training (Barkley 1997, 2000

Treating Irritability in Children:Interpersonal Social Rhythm TherapyTreating Irritability in Children:Interpersonal Social Rhythm Therapy

Standardized daily routines and social rhythms (Frank 1997)

Treatment for adults with bipolar disorder modified for youth

•Principles:– Regular sleep, exercise, socialization keeps people’s mood and behavior regular

– Converse: irregularities in sleep, exercise, socialization may be an early warning sign of problems/non-euthymic mood or behavior

Treating Irritability in Children: Family therapies Treating Irritability in Children: Family therapies

• Multi-family psychoeducational psychotherapy (Fristad 2009)

– Psychoeducation; build skills in mood sxmanagement, affect regulation, problem solving, communication

• Family-focused therapy (FFT)=CBT+psychoed+famtx -effective in adults and adolescents (Miklowtiz 2000, Pavuluri 2004)

– Psychoed about BD/tx; Communication & problem solving to reduce conflict/improve positive interactions

– For example “RAINBOW” (Pavuluri 2004)

• Multi-family psychoeducational psychotherapy (Fristad 2009)

– Psychoeducation; build skills in mood sxmanagement, affect regulation, problem solving, communication

• Family-focused therapy (FFT)=CBT+psychoed+famtx -effective in adults and adolescents (Miklowtiz 2000, Pavuluri 2004)

– Psychoed about BD/tx; Communication & problem solving to reduce conflict/improve positive interactions

– For example “RAINBOW” (Pavuluri 2004)

24

Treating Irritability in Children: Collaborative Problem SolvingTreating Irritability in Children: Collaborative Problem Solving

Collaborative Problem Solving (Greene 2003, 2004)•2 principles:

1) Social/emotional/behavioral issues for children should be understood from lagging cognitive skills—rather than attention-seeking, manipulative, limit-testing, poor motivation

2) Resolve these problems collaboratively—rather than reward/punishment

•3 steps:

1) Empathy Step: What is child’s concern about problem (chores, siblings, screen time)?

2) Define the Problem Step: Adult concerns

3) Brainstorm solution to address both

Dialectical Behavior Therapy (DBT) for AdolescentsDialectical Behavior Therapy (DBT) for Adolescents

Main target of which is emotion dysregulation, including high sensitivity to emotional stimuli and extreme emotional intensity

This adapted intervention is delivered over the course of one year, and is comprised of two modalities:

family skills training

individual psychotherapy with the adolescent patient.

Main target of which is emotion dysregulation, including high sensitivity to emotional stimuli and extreme emotional intensity

This adapted intervention is delivered over the course of one year, and is comprised of two modalities:

family skills training

individual psychotherapy with the adolescent patient.

71Goldstein T, Axelson D, Birmaher B, et al. J Am Acad Child Adolesc Psychiatry 2007; 46(7): 820-830.

Interpretation Bias Training Interpretation Bias Training

Targets hostile interpretation bias

Participants are presented with stream of faces depicting emotions

Training consists of 180 trials with goal of moving rating of ambiguous faces from angry to happy

Open study of DMDD subjects demonstrated significant reduction on parent rated irritability

Stoddard et al, 2016 JCAP 26 (1) 49-57

Targets hostile interpretation bias

Participants are presented with stream of faces depicting emotions

Training consists of 180 trials with goal of moving rating of ambiguous faces from angry to happy

Open study of DMDD subjects demonstrated significant reduction on parent rated irritability

Stoddard et al, 2016 JCAP 26 (1) 49-57

72

25

Irritability: Pharmacologic Management Irritability: Pharmacologic Management

Lithium = placebo

SSRIs = small impact alone - more in comb with stimulants

Stimulants = medium to large effect sizes

Atypical Antipsychotics = FDA approval in ASD

73

Case study : MaxCase study : Max

A 10-year-old boy presents to the outpatient clinic with a two year history of frequent temper tantrums in the context of frustration especially at home. He is described as “constantly cranky.”

His teachers also report that he is prone to get into fights during recess when he feels slighted. There is no trauma or social adversity that explains his presentation. He has no evidence of psychosis. Family history includes anxiety and depression in some relatives.

How would you proceed?

A 10-year-old boy presents to the outpatient clinic with a two year history of frequent temper tantrums in the context of frustration especially at home. He is described as “constantly cranky.”

His teachers also report that he is prone to get into fights during recess when he feels slighted. There is no trauma or social adversity that explains his presentation. He has no evidence of psychosis. Family history includes anxiety and depression in some relatives.

How would you proceed?

74

AACAP Presidential Initiative:

“It would be a shame if we jumped from the frying pan of mislabeling children as “bipolar” because we had no accurate diagnosis to categorize their explosivity—to the fire of conflating the mood & behavioral components of irritability”

Carlson G, J Child Psychol Psych 58;7 2018 740-43

“It would be a shame if we jumped from the frying pan of mislabeling children as “bipolar” because we had no accurate diagnosis to categorize their explosivity—to the fire of conflating the mood & behavioral components of irritability”

Carlson G, J Child Psychol Psych 58;7 2018 740-43

26

AcknowledgementsAcknowledgements

Ashley Martinez, BA

John Boekamp, PhD

Sarah Martin PhD

Heather Hunter, PhD

Maria Teresa Coutinho

The COBY Team and all the subjects

Ashley Martinez, BA

John Boekamp, PhD

Sarah Martin PhD

Heather Hunter, PhD

Maria Teresa Coutinho

The COBY Team and all the subjects

76

THANK YOU!THANK YOU!

[email protected][email protected]

77

Documents

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