Transcript HANDOUT Szatmari

Resiliency in ASD; A Missed
Translational Opportunity?
Peter Szatmari MD
Chief of the Child and Youth Mental Health
Collaborative
CAMH, SickKids and University of Toronto
Conflict of Interest
• Receive grant funding from CIHR, Genome
Canada, Autism Speaks (Canada and US),
NeuroDevNet, OBI
• Royalties from Guildford Press
• No consultancy or pharmaceutical fees
Learning Objectives
• To understand the interaction of risk and
protective factors in accounting for
“resiliency” in ASD
• To give examples of resiliency from the
literature on sex differences and natural
history studies in ASD
• To appreciate the translational opportunities
that a study of resiliency might mean for ASD
Resilience
• Resilience refers to individuals who have “better
than expected outcomes” in the face of adversity
• The adversity is usually an “external” event;
trauma, catastrophe, abuse, mental illness in a
parent
• Resilience originally considered an individual trait
that “protects” a child from adversity (IQ, social
skills are protective factors)
• Now thought to be a reflection of both individual
(biological/behavioural) and contextual variables
Risk Factors in ASD
• Sex; boys more frequently affected than girls
• ASD is a familial disorder;
– Disorder runs in families; SRR is roughly 10% (Risch et
al 2013)
– 20% of sibs of an older child with ASD are affected
with ASD (Ozonoff et al 2011)
– Another 10% have some other developmental
challenge (Charman et al 2013)
• Rare de novo and inherited genetic variants
account for an increasing number of cases of ASD
• These include SNV, indels, CNVs, chromosomal
There is evidence for “shared”
environmental factors
• These occur “in utero” during 1st trimester
– Prematurity
– Maternal diabetes
– Vit D and folic acid deficiency
– Pregnancy and birth complications
– Air pollution
• Probably examples of gene X environment
interactions
• ES very small and in need of replication
Resiliency in ASD
• What if the adversity is a diagnosis of ASD? Or
exposure to the risk factors for ASD?
• Then resiliency is doing “better than expected”
given a dx of ASD
• Or not developing ASD given a risk factor for ASD
• PubMed offers no citations on ‘resiliency” in the
child with ASD
• There are in fact many examples of resiliency in
ASD if one looks for heterogeneity in outcome
Three Examples of Resiliency
• Sex differences and the existence of protective
effects in girls
• Resilient outcomes seen over time in children
with ASD; mental health challenges
• Resiliency in parents
Sex differences
• Girls outnumber boys 4:1 in clinic samples, 2-3 :1
in community samples
• Increasing evidence that higher functioning girls
are less well recognized;
• Girls show fewer RSB, those with higher IQ also
better social communication skills
• Might have a different phenotype that is missed
• What is it that protects girls in the face of genetic
liability?
Three Predictions that follow from the
Multiple Threshold Model are
Confirmed
• Girls require a higher number of genetic risk
factors to show ASD (Jacquement et al 2014)
• Male relatives of affected females are at higher
risk of ASD than male relatives of affected males
(Werling & Geschwind 2015)
• Girls can carry the risk factor but not be affected
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Resilience in Natural History Studies of
ASD?
• Many longitudinal follow up studies of ASD
• Improvement in ASD symptoms but decline in
adaptive functioning relative to typical children
• Predictors of poor outcome; Lower IQ and no
useful speech by 5 years of age
• Problem has been that there is an unwarranted
assumption that course is homogeneous
• If test for heterogeneity, can look for resilient
trajectories and resilient outcomes
PATHWAYS IN ASD STUDY; A
LONGITUDINAL STUDY OF OUTCOMES
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Pathways in ASD
• Multi-site study of the natural history of ASD
• Following 420 newly diagnosed children (age 2-4)
into adolescence (8 data points so far, Phase III now
funded)
• Describe heterogeneous developmental trajectories
of children with ASD
• And the predictors of those trajectories
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Descriptive statistics
Gender
Male
Female
Site
Halifax
Montreal
Hamilton
Vancouver
Edmonton
Age at diagnosis
Age at study enrolment
M-P-R developmental index standard score
PLS-4 total language standard score
n
%
355
66
84.3
15.7
56
134
68
93
70
13.3
31.8
16.2
22.1
16.6
Mean
38.2
39.9
57.2
65.2
SD
8.8
9.0
26.2
19.2
What about Trajectories of Mental
Health Challenges?
• Increasing recognition of comorbidity with
mental health challenges; between 40%-60%
have comorbid ADHD or anxiety disorder
• Aggression, anxiety, temper tantrums, emotion
regulation
• All this is based on cross-sectional data
• Are there trajectories of internalizing problems
(anxiety/depression) and externalizing problems
(disruptive behaviours and ADHD)?
Implications of Ext/Int Trajectories
• Stability of heterogeneous trajectories
• These trajectories are “yoked”
• 1 very high risk group; high scores on both
(10%)
• But most kids moderate or low trajectories
• Family income predicts High risk status
• Girls more likely to be in the high internalizing
trajectory than boys
What about Resilient Families?
• Families with an ASD child experience more
stress than any other child disability
• Demographic factors; SES, ethnicity, family size
• Associated with several child characteristics;
aggression, repetitive behaviors, language and
cognitive difficulties
Impact of personal and social resources on parenting
stress in mothers of children with ASD (Zaidman-Zait,
Mirenda et al 2016)
• Stress is a function of resources available
• What variables are associated with stress?
Demographic, child characteristics?
• Or personal resources such as social supports,
family functioning, ways of coping?
• Question; what baseline (T1) variables predict
maternal stress at T2 (at 6 years of age or 2
years later)?
Variables (all at T1) that DO NOT
predict Stress at T2
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Maternal education
Household income
Marital status
Ethnicity
Externalizing behavior
Internalizing behavior
Repetitive behavior
Engaged problem coping
Disengaged emotion coping
Results of the final step of the hierarchical regression
for child and family variables predicting parenting
stress at T2.
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Overall parenting stress at diagnosis (T1)
Social support at T1
Family dysfunction at T1
Change in engaged problem coping
Change in disengaged emotion coping
Change in social support
Change in family dysfunction
Summary
• Resilient trajectories and outcomes; doing better
than expected given the dx or exposure to the
risk factor
• It is possible to be exposed to the risk factor and
NOT develop the disorder
• It is possible to have better than expected
trajectories in mental health symptoms given the
diagnosis
• Parental resilience largely a function of coping
strategies, social supports and family functioning
Many Unanswered Questions
• What accounts for resilient trajectories and
outcomes? At different stages and for
different domains?
• What is the interaction between parental and
child resilience?
• What interventions will promote resiliency
among all family members of a child with
ASD? Why are these interventions not
routinely available for family members?
Conclusions
• The resilience of each individual with ASD (or
each family member) is the result of the
interaction between risk and protective factors at
several levels (molecular to individual to
contextual)
• Focus of the field has been on the study of risk
factors and what predicts a poor outcome
• Instead a focus on factors that promote resiliency
may have a larger impact on QOL and long term
outcomes!
Acknowledgements
• Pathways team; Anat Zaidman-Zait, Pat
Mirenda, Eric Duku, Tracy Vaillancourt, Isabel M
Smith, Susan Bryson, Eric Fombonne, Joanne
Volden, Charlotte Waddell, Lonnie
Zwaigenbaum, Stelios Georgiades, Teresa
Bennett, Mayada Elsabaggh, Wendy Ungar, Mike
Chalupka, Ann Thompson
• Funding agencies and the families and kids
who participated in our studies