Experimental and Parent-Reported Self-Regulation in Infants at High- and Low-Risk for Autism

University of South Carolina Neurodevelopmental Disorders Lab, University of South Carolina
Bridgette Tonnsen, M.A. John Richards, Ph.D. Jane Roberts, Ph.D.

INTRODUCTION
Recent estimates suggest 1 in 54 males are diagnosed with an autism spectrum disorder (ASD), indicating a critical public health concern (CDC, 2012). Atypical self regulation is one of the earliest predictors of autism and is believed to contribute to later socio-communicative deficits. Infants who later meet criteria for autism have demonstrated difficulties disengaging visual attention (e.g. Elsabbagh et al., 2009, 2011; Zwaigenbaum et al., 2005) and modulating physiological arousal (e.g. Roberts et al., 2012) during the first year of life. However, no studies have examined the latent heterogeneity of early visual attention indicators by comparing data across high risk infant samples. The University of South Carolina Neurodevelopmental Disorders Lab is investigating the emergence of autism in two “high risk” infant samples: infant siblings of children with autism and infants with fragile X syndrome.
Infant siblings of children with autism (ASIBS) comprise the most commonly studied high-risk prospective sample, as ASIBS face higher rates of autism diagnoses (10-61%; e.g. Landa & Garrett-Mayer, 2006) than the general population (1-2%). Relevant to the present study, ASIBS have demonstrated difficulties disengaging attention during visual tasks (Elsabbagh et al., 2009, 11; Zwaigenbaum et al., 2005). Between 25% and 60% of infants with fragile X syndrome (FXS) later meet criteria for autism, and up to 90% display autistic symptoms. Fragile X syndrome is the most common heritable form of intellectual disability and the leading single-gene cause of autism, affecting 1:4000 individuals (Crawford et al., 2001). Recent work from our lab suggests longer time spent looking at a toy at 12m and increased latency to disengage attention between 9 and 12m relate to elevated autistic behavior in infants with FXS (Roberts et al., 2011).

METHODS: Gap Overlap Task
The Gap Overlap Task was provided courtesy of the Centre for Brain & Cognitive Development, Birkbeck, University of London. Reaction time (RT) to orient toward a peripheral target is measured across three phases: Baseline, Gap and Overlap.
Baseline trials: peripheral stimulus is presented as the central stimulus disappears Gap trial: central and peripheral stimuli are separated by a 200ms gap, cuing orienting Overlap trial: peripheral stimulus is presented while central stimulus is still on the screen

RESULTS: Parent-Reported Temperament
Contrary to our expectations, one-way ANCOVA analyses did not reveal significant differences among groups across parent-reported Orienting and Regulation (p’s>.05).
Parent Reported Orienting and Regulation
Subdomain Score: Marginal Mean 7 6 5 4 3 2 1 0 Low Pleasure Affiliation Duration of Orienting Soothability

v
v v

v
v v v

TD ASIB FXS

DISCUSSION
The present study includes pilot data from an ongoing longitudinal study of the emergence of autism in high risk infants. These data expand the current literature by comparing the presentation of potential early indicators across multiple high-risk infant groups. Key findings from pilot data suggest: - All groups show expected Disengagement and Facilitation effects - Infants with FXS show particular difficulties disengaging visual attention during a computerized orienting task - ASIBs and TD controls performed similarly, although this finding may relate to the high proportion of females in the ASIB group - Parent-reported Orienting and Regulation does not appear to differ among high- and low-risk groups. Future directions will include: - Continuing data collection through our ongoing longitudinal study - Examining the relationship behavioural performance and physiological indicators of attention - Examining moderating effects of age, gender and biological markers (e.g. FMRP and CGG Repeats in FXS) - Linking early patterns of self-regulation to later autism outcomes We hope these findings will eventually inform earlier detection, diagnosis and treatment of children affected by autism.

The “Facilitation Effect” suggests infants respond more quickly during Gap Trials due to the presence of a visual cue (blank screen).
Facilitation = - (Gap RT – Baseline RT)

The “Disengagement Effect” suggests that infants respond more slowly during Overlap due to the presence of competing stimuli.
Disengagement = Overlap RT – Baseline RT

RESULTS: Gap Overlap Task
Reaction Time Across Trials and Groups
Reaction Time Marginal Mean (s)

RESEARCH QUESTIONS
Do high and low-risk infants differ in self-regulation, as measured by: (a) maternal reports of temperament (b) disengagement and facilitation during a computerized attention task

Disengagemnt and Facilitation Across Groups
0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 Disengagement Facilitation
Reaction Time Marginal Mean (s)

1.6 1.4 1.2 1.0 0.8 0.6 0.4 0.2 0.0 Gap Overlap Baseline FXS (n=3) ASIB (n=8) TD (n=8)

FXS (n=3) ASIB (n=8) TD (n=8)

PARTICIPANTS
Preliminary data include participants from an ongoing longitudinal study investigating the emergence of autism in high risk infants.
Gap Overlap Task Data Parent-Reported Temperament

Mean Reaction Time (s)

1.2 1 0.8 0.6 0.4 0.2 0 Gap Overlap Baseline FXS (n=3) ASIB (n=5) TD (n=3)

Mean Reaction Time (s)

FXS ASIB Controls (TD) TOTAL

n n male 3 3 8 4 8 8 19 15

m age(SD) 9.67 (.53) 10.09 (2.91) 9.70 (2.35) 9.86 (2.35)

n 9 12 15 36

n male 6 10 11 27

Mean Age(SD) 11.3 (1.01) 7.59 (2.04) 8.87 (2.28) 9.05 (2.38)

All groups (n=19) demonstrated Disengagement and Facilitation Effects. Visual inspection of marginal means (controlling age) suggest infants with FXS show the greatest difficulty disengaging from central to peripheral stimuli. Given our small sample, these effects were not statistically significant using one-way ANCOVA, F(3, 15)=1.44, p=.27. However, group differences produced a moderate-sized effect (partial ŋ2=.22; Cohen, 1998).
9 Month Gap Overlap Task
1.6 1.4 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 Disengagement Facilitation

9 Month Gap Overlap Task Data

This work was supported by NIMH-1F31MH095318-01A1 (Tonnsen) and NIMH1R01MH090194-01A1 (Roberts). The Gap Overlap Task was provided courtesy of the Centre for Brain & Cognitive Development, Birkbeck, University of London.

FXS (n=3) ASIB (n=5) TD (n=3)

REFERENCES
Center for Disease Control (2012). Prevalence of Autism Spectrum Disorders – Autism and Developmental Disabilities Monitoring Network, 14 Sites, United States, 2008. Morbidity and Mortality Weekly Report: Surveillance Summaries, 61(SS03); 1-19. Crawford, D. C., Acuna, J. M., & Sherman, S. L. (2001). FMR1 and the fragile X syndrome: human genome epidemiology review. Genetics in Medicine, 3, 359-371. Elsabbagh, M., Holmboe, K. , Gliga, T., Mercure, E., Hudry, K. … & BASIS Team (2011). Social and attention factors during infancy and the later emergence of autism characteristics. Elsabbagh, M., Volein, A., Holmboe, K., Tucker, L., Csibra, G. … & Johnson, M. H. (2009). Visual orienting in the early broader autism phenotype: disengagement and facilitation. Journal of Child Psychology and Psychiatry, 50, 637-42. Gartstein, M. A., & Rothbart, M. K. (2003). Studying infant temperament via the Revised Infant Behaviour Questionnaire. Infant Behavior & Development, 26, 64-86. Landa, R., & Garrett-Mayer, E. (2006). Development in infants with autism spectrum disorders: a prospective study. Journal of Child Psychology and Psychiatry, 47, 629-638. Roberts, J.E., Hatton, D.D., Long, A.C.J., Anello, V., & Colombo, J. (2011). Visual attention and autistic behavior in infants with fragile X syndrome. Journal of Autism and Developmental Disorders. Epub ahead of print. Roberts, J. E., Tonnsen, B. L., Robinson, A. R., & Shrinkareva, S. (in press). Heart activity and autistic behavior in toddlers with fragile X syndrome. American Journal of Intellectual and Developmental Disabilities. Zwaigenbaum, L., Bryson, S., Rogers, T., Roberts, W., Brian, J., & Szatmari, P. (2005). Behavioral manifestations of autism in the first year of life. International Journal of Developmental Neuroscience, 23, 143-152.

METHODS: Parent-Reported Temperament
Mothers completed the Infant Behavior Questionnaire-Revised (IBQ-R; Gartstein & Rothbart, 2003), a 191 item measure of infant temperament. The Orienting/Regulation Scale of the IBQ-R measures regulatory functioning across several subdomains: Low Intensity Pleasure, Affiliation, Duration of Orienting, and Soothability.

Visual inspection of 9-month data (n=11) suggest infants with FXS show the greatest difficulty disengaging from central to peripheral stimuli. Contrary to our expectations, the ASIB group showed slightly stronger Disengagement than TD participants. The similar performance between ASIB and TD groups may relate to the inclusion of female ASIBs. These pilot data trends will be further examined as we continue collecting data.

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