autism in girls - iaccof females with autism network. this network has generated a comprehensive,...
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AUTISM IN GIRLS AND WOMEN
A PANELDISCUSSION
TUESDAY, SEPTEMBER 19, 2017 • 1:00 PM - 3:00 PM
NEUROSCIENCE CENTER (NSC)6001 EXECUTIVE BLVD • ROOM 7102
ABOUT THE SPEAKERS
KEVIN PELPHREY,PH.D.Carbonell Family ProfessorDirector, Autism and Neurodevelopmental DisordersInstitute at George Washington University and Children’s National MedicalCenter
Dr. Kevin Pelphrey is the Carbonell Family Professor and Director of the Autism & Neurodevelopmental Disorders
Institute at George Washington University (GW) and Children’s National Health System (CNHS) in Washington, DC. The Institute serves as a focal point for translational research and comprehensive clinical services for people living with Autism Spectrum Disorder (ASD). His program of research investigates the brain basis of neurodevelopmental disorders to develop biologically-based tools for detection, stratification,and individually tailored treatments. Dr. Pelphrey is also the Principal Investigator of the NIH ACE-Multimodal Developmental Neurogeneticsof Females with Autism network. This Network has generated a comprehensive, multi-level (gene-brain-behavior) data from large and diverse cohorts of young women and men with ASD. Dr. Pelphrey joined the Interagency Autism Coordinating Committee as a public member in 2015. He is the father of a son and a daughter on the autismspectrum.
PAMELA VENTOLA,PH.D.Assistant Professor, Yale Child StudyCenter
Dr. Pamela Ventola is a clinical psychologist and Assistant Professor at the Yale Child Study Center. Her clinical work and research program focus on behavioral treatment for ASD, specifically,Pivotal Response Treatment (PRT).She also has a strong interest in girls and women with ASD. She has
conducted several studies on sex-based differences in treatment response, and she is currently collaborating with Dr. Kevin Pelphrey on a multi-site study related to the neurogenetics of females with ASD. Dr. Ventola is heavily involved in the clinical components of this multi-site program. Additionally, she is commencing a study withDr. Pelphrey to assess the effects of oxytocin as an enhancer of response to PRT. Evaluating sex-based differences to this combination treatment is a key aim of the newproject.
ZOEGROSSDirector of Operations, Autistic Self Advocacy Network
Zoe Gross is Director of Operations at Autistic Self Advocacy Network. Previously, she workedas a special assistant atthe Administration for Community Living, and as a policyanalyst on Senator Tom Harkin’s Health, Education, Laborand Pensions Committee staff. In 2012, Zoe created the
annual Disability Day of Mourning vigil, a national, cross-disability event which commemorates the lives of disabled people murdered by their family members or caregivers.
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ABOUT AUTISM IN GIRLS AND WOMEN: A PANEL DISCUSSION
Recent advances in research suggest that autism spectrum disorder (ASD) presents differently in males andfemales.As a result, researchers are seeking to understand the biological differences between ASD in males and females, as well as reevaluating the effectiveness of diagnostic tools and treatments for females on theautism spectrum. Meanwhile, girls and women with ASD are sharing their stories in order to increase awareness among researchers and the general public. This panel discussion will present three different perspectives on understanding ASD in girls and women.
Dr. Kevin Pelphrey will be speaking on biological aspects of sex differences in ASD, Dr. Pamela Ventola will be speaking on observable differences in phenotype between girls and boys, and Ms. Zoe Gross will be speaking on personal and community experiences related to ASD in girls and women.
SPONSORED BY ORDGMH AND OARC
AGENDA
1:00 PM –1:10 PM INTRODUCTORY REMARKS
Susan Daniels, Ph.D.Director, Office of Autism ResearchCoordination, National Institute of Mental Health
Executive Secretary, Interagency Autism Coordinating Committee
Tamara Lewis Johnson, M.P.H., M.B.A.Health Scientist Administrator, Office for Research on Disparities and Global Mental Health, National Institute of Mental Health
Chief, Women’s Mental Health ResearchProgram
1:10 PM –1:30 PM
Kevin Pelphrey, Ph.D.Carbonell FamilyProfessor
Director, Autism and Neurodevelopmental Disorders Institute at George Washington University and Children’s National Medical Center
1:30 PM –1:50 PM
Pamela Ventola,Ph.D.Assistant Professor, Yale Child StudyCenter
1:50 PM –2:10 PM
Zoe GrossDirector of Operations, Autistic Self AdvocacyNetwork
2:10 PM –3:00 PMQUESTION AND ANSWER PANEL DISCUSSION
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S L I D E 4
NIH Autism Center of Excellence: Girls' (Women's) Neurogenetics Network
Kevin Pelphrey & the Girls’ Network TeamAutism & Neurodevelopmental Disorders Institute
www.autism.gwu.edu
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S L I D E 5
NIH Autism Center of Excellence:Girls' (Women's) Neurogenetics Network
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S L I D E 6
Network Aims
1) Identify sex differences in ASD brain development leading to gender specific biomarkers to inform treatment selection & response. 2) Bridge DNA sequence and brain development.
3) Relate neural signatures to behavior and genetics (structure & expression) to predict behavioral trajectories.
4) Collaborate with ASD self-advocates / participants to evaluate the experiential validity of our findings.
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S L I D E 7
Systems Biology Approach
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Social vs. Non‐Social Motion
Kaiser et al. (2010) Proceedings of the National Academy of Sciences
S L I D E 8
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S L I D E 9
R
R
R
State: ASD < TD & ASD < USTrait: US < TD & ASD < TDCompensatory: US > TD & US > ASD
Kaiser et al. (2010) Proceedings of the National Academy of Sciences
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S L I D E 10
Informative at the level of the individual child?
Discovery Replication
?
Malin Björnsdotter, PhD
Björnsdotter et al., JAMA: Psychiatry, 2016
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S L I D E 11
Björnsdotter et al., JAMA: Psychiatry, 2016
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S L I D E 12
Allison Jack, PhD
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S L I D E 13
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S L I D E 14
Archana Venkataraman, PhD
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S L I D E 15
Girls –Network to Construct mapping
Boys –Network to Construct mapping
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S L I D E 16
Problem: Lack of predictive autism biomarkers perpetuates the status quo of imprecise treatments, wasted time & resources.
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S L I D E 17
Pivotal Response Training (PRT)
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S L I D E 18
Change in Behavior: Social Responsiveness Scale (SRS)
Yang et al. (2016) Translational Psychiatry
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S L I D E 19
Increase in severity
Decrease in severity
Predicted change in severity
Actu
al c
hang
e in
seve
rity
r = .85, p < .0001
y = -50 mm y = -52 mm
y = 18 mm y = -4 mm
Cluster 1 Cluster 2
Cluster 3 Cluster 4
-0.06 0.04weights
R
Neuro-prediction of treatment response
Yang et al. (2016) Translational Psychiatry
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S L I D E 20
Linking genes, brain, & behavior in the longitudinal study of infants social brain development
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S L I D E 21
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S L I D E 22
-0.06
-0.01
0.04
0.09
0.14
1 11 21 31 41 51 61 71 81 91 101
111
121
131
141
151
Hem
oglo
bin
chan
ge
(mic
rom
olar
)
Time (in tenths of seconds)
Low Risk
BIOLOGICAL
SCRAMBLED
-0.06
-0.01
0.04
0.09
0.14
1 11 21 31 41 51 61 71 81 91 101
111
121
131
141
151
Hem
oglo
bin
chan
ge
(mic
rom
olar
)
Time (in tenths of seconds)
Low Risk
BIOLOGICAL
SCRAMBLED
-0.06
-0.01
0.04
0.09
0.14
1 11 21 31 41 51 61 71 81 91 101
111
121
131
141
151Hem
oglo
bin
chan
ge
(mic
rom
olar
)
Time (in tenths of seconds)
High Risk
BIOLOGICAL
SCRAMBLED
-0.06
-0.01
0.04
0.09
0.14
1 11 21 31 41 51 61 71 81 91 101
111
121
131
141
151
Hem
oglo
bin
chan
ge
(mic
rom
olar
)
Time (in tenths of seconds)
High Risk
BIOLOGICAL
SCRAMBLED
LEFT RIGHT
Results: fNIRS (LR and HR 3-Month-Old Infants)
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S L I D E 23
Universal Screening?
3,600 births per year representing all ethnicities, classes, backgrounds – a population-based sample
Ashley Darcy-Mahoney, PhD, NNP, FAAN
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S L I D E 24
AcknowledgmentsNIMH NICHDNINDSThe Carbonell FamilyThe Harris FamilyThe Dietz FamilySimons FoundationAutism SpeaksHilibrand FoundationJohn Merck Scholars FundAutism Science Foundation
We thank the participants and their families for participating in our research.We thank my colleagues who make this work so much fun.
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Girls and Women with ASD–Clinical Perspectives
Pam Ventola, PhDAssistant Professor
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Learning Objectives
• Identify clinical differences between females and males with ASD
• Describe factors related to misdiagnosis or delayed diagnosis in females with ASD
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Differential Prevalence
• Sex Ratio 4:1; as high as 8:1 in individuals with IQ > 70
• Girls diagnosed later than boys– Mean age of 3 years for boys– Mean age of 4 years for girls
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Boys and Girls Differ
• Girls and boys are different.• Biological? Socially constructed?
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Social Demands Differ
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Differences in Social Expectations
• Boys (and men):
• Large stable groups; rough and tumble play; competitive team games; socialize through activities
• Girls (and women):
• Small groups; conversational; intimacy through sharing
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The Classic Female Phenotype
• Often, girls with ASD compared to boys with ASD:
• Lower cognitive abilities
• More severe social communication deficits
• Fewer externalizing behaviors
• Fewer repetitive behaviors/restricted interests
• What about the more cognitively able girls?
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Females and Males with IQ >70
• Boys with ASD
• More isolative
• Unusual interests (mayors, portable toilets, schedules)
• Disruptive behaviors
• Girls with ASD
• Strong interests but consistent with TD peers
• Greater internalizing symptoms (anxiety, depression)
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Case Vignette
• Diagnosed with ASD at 4 years old
• Nonverbal skills ~ 2.5 year level; Language skills ~ 2 year level
• “Talked” constantly
• Flitted about, repetitively “dancing”
• Hyper-focused on own reflection
• Fixated on Disney princesses
• Very directive and rigid
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Case Vignette
• 10 year old girl with ASD
• Nonverbal abilities: below average; verbal abilities: average
• Highly socially motivated, outgoing, and talkative
• No disruptive behaviors
• “Hyper-feminine”
• Focused on style, celebrities, boys
• Fixated on peers
• Learn about peers, follow peers, want to be close to peers (over-bearing to others)
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Why are we missing or delaying diagnosis of ASD in girls?
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Standardized Diagnostic Measures
• Biased towards typical ASD male presentation
• Girls report problems with relationships but teachers report fewer symptoms
• Clinical settings- boys are more active and outwardly atypical
• Boys have more atypical interests and more repetitive behaviors
• Easier to identify as RRBs
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Girls with ASD Mask Difficulties?
• Elementary school-aged children (Dean et al., 2017)
• Girls with ASD maintain physical proximity but not engagement
• Girls are flitting in and out of social groups
• Adults see girls with ASD together with other girls, but peers detect differences
• Boys with ASD were more isolative
• Boys have trouble initiating and sustaining
• Adults see boys as being excluded/alone
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Continuing to Mask Inherent Difficulties
• Adults with ASD also “camouflage” symptoms
• Use learned jokes, follow social scripts, mimic others’ gestures/facial expressions
• Adopt persona from peer or fictional character
• Women use these camouflaging strategies more readily and often (Lai et al., 2017)
• Camouflaging may bring increased stress and anxiety; “exhausting to be someone you are not”
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Delayed or Misdiagnosis in Females
• Differing gender-based expectations
• Differing presentations
• Function of bias in diagnostic instruments
• Compensatory strategies (masking/camouflaging)
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Treatment and Support for Girls with ASD
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Behavioral Interventions
• Multiple evidence-based naturalistic behavioral interventions
• Pivotal Response Treatment (PRT)
• Combines applied behavior analysis principles with motivational strategies
• Focuses on pivotal areas with widespread change in functioning
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Supporting Girls with ASD
28 children; 16 boys/12 girls (4-7 years) received PRT
4-month treatment course
8 hours per week
Direct work with child & parent in clinic & home
Variable M SD
Age 5.48 0.85
DAS-II 102.8 16.7
CELF-4 Core Language
103.5 13.7
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Supporting Girls with ASD
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Supporting Girls with ASD
0
20
40
60
80
100
120
SRS
Tota
l Sco
re
Baseline
SRS Total Score
Female
Male
Post-Treatment
• Overall improvement in social communication skills
• No sex-based differential in improvement
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Acknowledgements
We are grateful for funding from:• NIMH• NIH • Simons Foundation• Deitz Family• Esme Usdan and Family• Schmid Family• Dwek Family• Women’s Health Research at Yale• Autism Science Foundation
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Autistic Women and Girls& Research
• More autistic people exist than have been diagnosed• Underdiagnosis widens this gap for women and people of color
• Diagnostic disparities research diagnostic disparities research….
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Autistic Women and Girls& Diagnosis
• Common experiences of being diagnosed
• Consequences of not having a diagnosis
• Consequences of getting diagnosed
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Autistic Women and Girls& Myths About Autism
• Empathy
• “Extreme maleness”
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Autistic Women and GirlsStruggles
• Health care
• Autistic women and girls face violence and abuse
• Employment
• Access to community-based services
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Autistic Women and GirlsStrengths
• Autistic people & strengths (generally)
• Resilience
• We want a better future for autistic children & adults
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What is the best way to address the needs of autistic girls & women?
• Ask us
Autistic Self Advocacy Network: autisticadvocacy.orgAutism Women’s Network: autismwomensnetwork.orgAcademic Autism Spectrum Partnership in Research and Education: aaspire.org