recent findings in neurobiology, clinical manifestations...

Recent Findings in Neurobiology, Clinical Manifestations and Diagnosis

MA. ROCHELLE BUENAVISTA - PACIFICO, MD, FPPS, FPSDBP

Philippine Society for Developmental and Behavioral Pediatrics 9th Biennial ConventionNovotel, Quezon City, September 5, 2017

DIVERSITY IN ADHD

A brain disorder marked by an ongoing pattern of inattention and/or hyperactivity-impulsivity that is inconsistent with a child’s

level of development. • are more severe• occur more often• interfere with or reduce the quality of how

they functions socially, at school, or in a job

National Institute of Mental Health

ATTENTION DEFICIT / HYPERACTIVITY DISORDER

MRBPacifico_05SEP2017


Evolution of nomenclature used to describe ADHD

Prevalence of ADHD in children and adolescents by geographical location (n=102 studies)

Polanczyk G, de Lima MS, Horta BL, et al. The worldwide prevalence of ADHD: a systematic review and metaregression analysis. Am J Psychiatry 2007; 164: 942-948.

Worldwide estimates = 5 – 7%MRBPacifico_05SEP2017


Philippine Estimates of AD/HD Prevalence

Prevalence: 3 - 5%

Population: 103.3 M

AD/HD: 3-5.1 M

0

2

4

6

8

10

12

2003 2007 2011

Maternal and Child Health Bureau and the National Center for Health Statistics of the U.S. Centers for Disease Control and Prevention in a National Children's Survey from 2003-2011

Prevalence rates of ADHD Diagnosis among children and adolescents aged 4 to 17 years

55% increase in diagnosis among girls from 2003 to 2011

M:F ( 4:1)

52% increase among adolescents

50% increase among younger children

%


"Mild" ADHD diagnosed at 7 years,

"Moderate" ADHD diagnosed at 6.1 years

"Severe" ADHD diagnosed at 4.4 years.

The more severe the symptoms, the younger they are identified and the earlier intervention can be started

Thomas, Rae et al. (April 2015). Prevalence of Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-analysis. Pediatrics, 135(4), pp. e994–e1001.

Pastor, Pastor N. et al. (2015). Association between diagnosed ADHD and selected characteristics among children aged 4–17 years: United States, 2011–2013. NCHS data brief, no 201. Hyattsville, MD: National Center for Health Statistics.MRBPacifico_05SEP2017

Average age of diagnosis = 6.2 yrs old

ETIOLOGY


EPIGENETIC BASIS OF ADHD

ADHD


EPIGENETIC BASIS OF ADHD

Screens and ADHD ….Overstimulation hypothesis :

Christakis D. Rethinking ADHD. JAMA Pediatrics.2016; 170(2):109-110MRBPacifico_05SEP2017

Overstimulating the brain in the first years of life will condition it to expect high levels of input leading to shorter attention spans later

”I’m bored!”

“aren’t youalways?!”

TOYS

Attentional and Self-regulatory Problems from early screen exposure:

10% increase for every hour of television viewing per day in children < 3 yrs old

Further increase with fast-paced videos

110% increase if violent games

Christakis D. Rethinking ADHD. JAMA Pediatrics.2016; 170(2):109-110Zimmerman etal. Association between content type of early media exposure and

subsequent attentional problems. Pediatrics, 2007. 120(5) MRBPacifico_05SEP2017

Children who can’t pay ATTENTION

can’t LEARN!

Christakis 2004, Small 2008 as cited in Rowan, 2015MRBPacifico_05SEP2017

“High speed media content can contribute to ATTENTION

DEFICIT, as well as decreased concentration and memory, due

to the brain pruning neuronal tracks to the frontal cortex."

How Neurotransmission Workshttps://www.youtube.com/watch?v=p5zFgT4aofA

Neurobiology OF ADHD

Basal ganglia (putamen, nucleus accumbens)

Cerebellum

Frontal Lobe

Amygdala


NEUROBIOLOGY OF ADHD

Hippocampus

Basal ganglia (putamen, nucleus accumbens)Frontal Lobe


Hoogman M, et al. Subcortical brain volume differences in participants with attention deficit hyperactivity disorder in children and adults: a cross-sectional mega-analysis. Lancet Psychiatry. Feb. 15, 2017,

Shaw P, etal. Development of cortical surfaces and gyrification in AD/HD.. Biological Psychiatry, 2012

“HOW”

Basal ganglia (putamen, nucleus accumbens)

Cerebellum(vermis)

Frontal Lobe




“WHEN”

Frontal Lobe

Amygdala




Hippocampus

“WHY”

*Lighter colored areas indicate peak

cortical maturation

FrontalLobe

Brain Imaging Studies comparing maturation of Frontal Lobes of Individuals with and without ADHD

Courtesy of ADHD Institute MRBPacifico_05SEP2017


> Frontal Lobe size reduction> Temporal lobe size reduction> Decreased activity in both

MRI Differences between ADHD and Control brains



MRI Studies show less blood flow in regions of the brain while working on a task in individuals with ADHD vs. Non-ADHD



DIAGNOSIS and

CLASSIFICATION

CORE SYMPTOMS OF AD/HD:

(EXECUTIVE FUNCTIONS)2. Hyperactivity 3. Impulsivity


Emotional Dysregulation

1. Inattentiveness(SELF-REGULATION)

AD/HD Mimickers

Sudden change in the child’s life (ex: death of a parent, divorce, parent’s job loss)

Undetected seizures Intermittent hearing problems

(ex: middle ear infection)

Other medical disorders that affect brain functioning

Underachievement caused by Learning Disability

Anxiety or depression


DSM – 5 (American Psychiatric Association)ICD-10( World Health Organization )

Rating scales:• ADHD-RS• Vanderbilt• SNAP-IV• Conners• SKAMP• ACE

Diagnosis and Assessment


Comprehensive Assessment tools

Neuroimaging Studies (ex: MRI, PET Scans)

Diagnosis and Assessment


(ex: Intelligence/Mental Development tests, Educational Achievement tests)

Electrometric Tests (ex: EEG)

Diagnostic and Statistical Manual of Mental Disorders Published by the American

Psychiatric Association Provides standard diagnostic criteria First edition (DSM-1) published in

1952 Most recent edition: DSM-5 (2013)


• Examples added for almost all criterion items• Age of onset: 12 (7 in DSM-IV)• Subtypes replaced with presentation specifiers

Combined presentationPredominantly inattentive presentationPredominantly hyperactive/impulsive presentation

• Comorbidity with ASD is allowed• Symptom threshold: 5 for adults, 6 for younger persons• Several symptoms (not impairment) present in more

than one settingMRBPacifico_05SEP2017

ADHD: Changes in the DSM-5CHANGES IN THE DSM-5

Examples added especially for adult presentationAge of onset: Before 12 years old (7 years old in DSM-IV)Subtypes replaced with presentation specifiers: Combined presentation Predominantly inattentive presentation Predominantly hyperactive/impulsive presentationComorbidity with ASD is allowedSymptom threshold: 5 for > 17 years, 6 for younger personsSeveral symptoms (not impairment) present in more than one setting

MRBPacifico_05SEP2017American Psychiatric Association. Diagnostic and Statistical Manual of Mental

Disorders, Fifth Edition. 2013.

DSM – 5 CLASSIFICATION for a DIAGNOSIS OF AD/HD

Before 12 years

At least 6 months

Present in > 2 settings

Impact on social, academic and occupational functioning

Not better accounted for by another mental disorder

Requires indication of severity

DISTRIBUTION ACCORDING TO AD/HD PRESENTATION

Faraone SV, Biederman J, Weber W, et al. Psychiatric, neuropsychological, and psychosocial features of DSM-IV subtypes of attention-deficit/hyperactivity disorder: results from a clinically

referred sample. J Am Acad Child Adolesc Psychiatry 1998; 37: 185-193.MRBPacifico_05SEP2017

COMBINED

INATTENTIVE

HYPERACTIVE-IMPULSIVE

61%30% 9%

Prevalence of AD/HD presentations according to age range

Willcutt EG. The prevalence of DSM-IV attention-deficit/hyperactivity disorder: a meta-analytic review. Neurotherapeutics 2012; 9: 490-499.MRBPacifico_05SEP2017

Diagnosed with only AD/HD

Diagnosed with 1 co-morbiddisorder

Diagnosed with 2 co-morbiddisorders

Diagnosed with 3 or moreco-morbid disorders

33%33%

18%16%

N = 5000 children

MedPage TodayMRBPacifico_05SEP2017

Distribution of Children with AD/HD in association with Co-morbid conditions

Cuffe, S.P., etal. Attention-Deficit/Hyperactivity Disorder and Psychiatric Comorbidity: Functional Outcomes in a School-Based Sample of Children. Journal of Attention Disorders.

Published online before print, November 25, 2015, doi: 10.1177/1087054715613437MRBPacifico_05SEP2017

Percent of children with certain problems, by disorder group

AD/HD will persist in approximately 50 – 75% of children diagnosed with the

condition

Caye A, etal. Predictors of persistence of ADHD into adulthood: a systematic review of literature and meta-analysis. Eur Child Adolesc Psychiatry. 2016 Nov;25(11):1151-1159.

Predictors of Persistence of ADHD into Adulthood

Severity

Need for treatment

Co-morbid conduct disorders

Co-morbid major depressive disorder

Kessler ,RC et al. Arch Gen Psychiatry 2010; 67:1168-1178


https://www.ncbi.nlm.nih.gov/pubmed/27021056

Associated Conditions1.Learning Disabilities ( 30-60%)

a. Dyslexiab. Dyscalculiac. Dysgraphia

2. Problems in Fine Motor Coordination (Dyspraxia) (50%)

3. Externalizing behavior Problems (50-60%)a. Oppositional Defiant Disorderb. Conduct Disorder

4. Internalizing Behavior Disorder (30%)a. Anxiety/Mood disorder

5. Language/Communication Disorder (Dysphasia)6. Tic Disorder7. Nocturnal Enuresis/Encopresis


Impact of ADHD across the lifespan


Executive Functions Impaired in ADHD

Executive Functions(Work together in various combinations)

Organizing, prioritizing

and activating to work

Focusing, sustaining

and shifting

attention to tasks

Regulating alertness, sustaining effort, and processing

speed

Utilizing working memory

and accessing

recall

Managing frustration

and modulatingemotions

Monitoring and self-

regulating action

1. Activation

2. Focus

3. Effort

4. Memory

5. Emotion

6. Action

TE Brown (2001) Manual for Attention Deficit Disorder Scales for Children and Adolescents

Problem Behaviors associated with ADHD compared to those without ADHD


Perceived negative impact of ADHD on everyday life of children and adolescents

Caci H, et al. Daily life impairments associated with self-reported childhood/adolescent AD/HD and experiences of diagnosis and treatment: results from the European Lifetime Impairment Survey. Eur Psychiatry 2014; 29: 316-323MRBPacifico_05SEP2017

Harpin V. 2005. The Effect of AD/HD on the Life of an Individual, their Families and Community from Pre-school to Adult life. Arch of Dis in Childhood MRBPacifico_05SEP2017

Developmental Impact of ADHD

PreschoolSchool-age

AdolescentCollege-age

Adult

BehavioralDisturbance

Behavioral DisturbanceAcademic Problems

Difficulty with social interactionSelf esteem issues

Academic ProblemsDifficulty with social interaction

Self esteem issuesLegal Issues, smoking and injury

Academic FailureSelf esteem issuesSubstance abuseInjury, accidents

Occupational difficulties

Self esteem issuesRelationship problems

Substance abuseInjury, accidents

Occupational Failure

Some Positive AD/HD Traits

ProductiveMulti-taskResourcefulAchieverAmbitious Broad mindedConceptualizes wellTenaciousTolerantDrivenOptimisticEmpathetic


HYPER-FOCUSED

AdaptiveCollaborativeAdventurous CourageousConfidentEloquent speakersUnconventionalCreativeInnovativeImaginativeVersatileMulti-talented


HYPER-FOCUSED

IMPULSIVE UNINHIBITED

Out goingWittyFunnyExcitingLivelyGood story-tellerAttractive personality CharismaticSociableSpontaneousPragmatic


HYPER-FOCUSED

IMPULSIVE UNINHIBITED

ATTENTION-SEEKING

ADHD

To Conclude:

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