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Journal of Neurodevelopmental Disorders
Published in: Journal of Neurodevelopmental Disorders 1/2019

Open Access 01-12-2019 | Autism Spectrum Disorder | Research

Differentiating social preference and social anxiety phenotypes in fragile X syndrome using an eye gaze analysis: a pilot study

Authors: Michael P. Hong, Eleanor M. Eckert, Ernest V. Pedapati, Rebecca C. Shaffer, Kelli C. Dominick, Logan K. Wink, John A. Sweeney, Craig A. Erickson

Published in: Journal of Neurodevelopmental Disorders | Issue 1/2019

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Abstract

Background

Fragile X syndrome (FXS) is the leading inherited cause of autism spectrum disorder, but there remains debate regarding the clinical presentation of social deficits in FXS. The aim of this study was to compare individuals with FXS to typically developing controls (TDC) and individuals with idiopathic autism spectrum disorder (ASD) across two social eye tracking paradigms.

Methods

Individuals with FXS and age- and gender-matched TDC and individuals with idiopathic ASD completed emotional face and social preference eye tracking tasks to evaluate gaze aversion and social interest, respectively. Participants completed a battery of cognitive testing and caregiver-reported measures for neurobehavioral characterization.

Results

Individuals with FXS exhibited reduced eye and increased mouth gaze to emotional faces compared to TDC. Gaze aversive findings were found to correlate with measures of anxiety, social communication deficits, and behavioral problems. In the social interest task, while individuals with idiopathic ASD showed significantly less social preference, individuals with FXS displayed social preference similar to TDC.

Conclusions

These findings suggest fragile X syndrome social deficits center on social anxiety without the prominent reduction in social interest associated with autism spectrum disorder. Specifically designed eye tracking techniques clarify the nature of social deficits in fragile X syndrome and may have applications to improve phenotyping and evaluate interventions targeting social functioning impairments.
Literature
1.
2.
Dictenberg JB, Swanger SA, Antar LN, Singer RH, Bassell GJ. A direct role for FMRP in activity-dependent dendritic mRNA transport links filopodial-spine morphogenesis to fragile X syndrome. Dev Cell. 2008;14(6):926–39.PubMedPubMedCentralCrossRef
3.
Baumgardner TL, Reiss AL, Freund LS, Abrams MT. Specification of the neurobehavioral phenotype in males with fragile X syndrome. Pediatrics. 1995;95(5):744–52.PubMed
4.
Mazzocco MM. Advances in research on the fragile X syndrome. Ment Retard Dev Disabil Res Rev. 2000;6(2):96–106.PubMedCrossRef
5.
Cordeiro L, Ballinger E, Hagerman R, Hessl D. Clinical assessment of DSM-IV anxiety disorders in fragile X syndrome: prevalence and characterization. J Neurodev Disord. 2011;3(1):57.PubMedCrossRef
6.
Bailey DB, Raspa M, Olmsted M, Holiday DB. Co-occurring conditions associated with FMR1 gene variations: findings from a national parent survey. Am J Med Genet A. 2008;146(16):2060–9.CrossRef
7.
Cornish K, Turk J, Hagerman R. The fragile X continuum: new advances and perspectives. J Intellect Disabil Res. 2008;52(6):469–82.PubMedCrossRef
8.
Hagerman RJ, Berry-Kravis E, Kaufmann WE, Ono MY, Tartaglia N, Lachiewicz A, et al. Advances in the treatment of fragile X syndrome. Pediatrics. 2009;123(1):378–90.PubMedPubMedCentralCrossRef
9.
Berry-Kravis E, Potanos K. Psychopharmacology in fragile X syndrome—present and future. Dev Disabil Res Rev. 2004;10(1):42–8.
10.
Bailey A, Bolton P, Butler L, Couteur A, Murphy M, Scott S, et al. Prevalence of the fragile X anomaly amongst autistic twins and singletons. J Child Psychol Psychiatry. 1993;34(5):673–88.PubMedCrossRef
11.
12.
Hagerman RJ, Hagerman PJ. Fragile X syndrome: diagnosis, treatment, and research. 3rd ed. Baltimore: John Hopkins University Press; 2002.
13.
Caglayan AO. Genetic causes of syndromic and non-syndromic autism. Dev Med Child Neurol. 2010;52(2):130–8.PubMedCrossRef
14.
Cohen D, Pichard N, Tordjman S, Baumann C, Burglen L, Excoffier E, et al. Specific genetic disorders and autism: clinical contribution towards their identification. J Autism Dev Disord. 2005;35(1):103–16.PubMedCrossRef
15.
Hagerman RJ, Rivera SM, Hagerman PJ. The fragile X family of disorders: a model for autism and targeted treatments. Curr Pediatr Rev. 2008;4(1):40–52.CrossRef
16.
Hong MP, Guilfoyle JL, Mooney LN, Wink LK, Pedapati EV, Shaffer RC, et al. Eye gaze and pupillary response in Angelman syndrome. Res Dev Disabil. 2017;68:88–94.PubMedCrossRef
17.
Baptista P, Mercadante M, Macedo E, Schwartzman J. Cognitive performance in Rett syndrome girls: a pilot study using eyetracking technology. J Intellect Disabil Res. 2006;50(9):662–6.PubMedCrossRef
18.
Sweeney JA, Takarae Y, Macmillan C, Luna B, Minshew NJ. Eye movements in neurodevelopmental disorders. Curr Opin Neurol. 2004;17(1):37–42.PubMedCrossRef
19.
20.
Klin A, Jones W, Schultz R, Volkmar F, Cohen D. Visual fixation patterns during viewing of naturalistic social situations as predictors of social competence in individuals with autism. Arch Gen Psychiatry. 2002;59(9):809–16.PubMedCrossRef
21.
Klin A, Lin DJ, Gorrindo P, Ramsay G, Jones W. Two-year-olds with autism orient to non-social contingencies rather than biological motion. Nature. 2009;459(7244):257.PubMedPubMedCentralCrossRef
22.
Shaffer RC, Pedapati EV, Shic F, Gaietto K, Bowers K, Wink LK, et al. Brief report: diminished gaze preference for dynamic social interaction scenes in youth with autism spectrum disorders. J Autism Dev Disord. 2017;47(2):506–13.PubMedCrossRef
23.
Dalton KM, Nacewicz BM, Johnstone T, Schaefer HS, Gernsbacher MA, Goldsmith HH, et al. Gaze fixation and the neural circuitry of face processing in autism. Nat Neurosci. 2005;8(4):519.PubMedPubMedCentralCrossRef
24.
Dalton KM, Nacewicz BM, Alexander AL, Davidson RJ. Gaze-fixation, brain activation, and amygdala volume in unaffected siblings of individuals with autism. Biol Psychiatry. 2007;61(4):512–20.PubMedCrossRef
25.
Farzin F, Rivera SM, Hessl D. Brief report: visual processing of faces in individuals with fragile X syndrome: an eye tracking study. J Autism Dev Disord. 2009;39(6):946–52.PubMedPubMedCentralCrossRef
26.
Farzin F, Scaggs F, Hervey C, Berry-Kravis E, Hessl D. Reliability of eye tracking and pupillometry measures in individuals with fragile X syndrome. J Autism Dev Disord. 2011;41(11):1515–22.PubMedPubMedCentralCrossRef
27.
Hessl D, Glaser B, Dyer-Friedman J, Reiss AL. Social behavior and cortisol reactivity in children with fragile X syndrome. J Child Psychol Psychiatry. 2006;47(6):602–10.PubMedCrossRef
28.
Hall SS, Frank MC, Pusiol GT, Farzin F, Lightbody AA, Reiss AL. Quantifying naturalistic social gaze in fragile X syndrome using a novel eye tracking paradigm. Am J Med Genet B Neuropsychiatr Genet. 2015;168(7):564–72.PubMedPubMedCentralCrossRef
29.
Hall SS, Lightbody AA, Huffman LC, Lazzeroni LC, Reiss AL. Physiological correlates of social avoidance behavior in children and adolescents with fragile X syndrome. J Am Acad Child Adolesc Psychiatry. 2009;48(3):320–9.PubMedPubMedCentralCrossRef
30.
Guillon Q, Hadjikhani N, Baduel S, Rogé B. Visual social attention in autism spectrum disorder: insights from eye tracking studies. Neurosci Biobehav Rev. 2014;42:279–97.PubMedCrossRef
31.
Dalton KM, Holsen L, Abbeduto L, Davidson RJ. Brain function and gaze fixation during facial-emotion processing in fragile X and autism. Autism Res. 2008;1(4):231–9.PubMedPubMedCentralCrossRef
32.
Watson C, Hoeft F, Garrett AS, Hall SS, Reiss AL. Aberrant brain activation during gaze processing in boys with fragile X syndrome. Arch Gen Psychiatry. 2008;65(11):1315–23.PubMedPubMedCentralCrossRef
33.
Wang J, Ethridge LE, Mosconi MW, White SP, Binder DK, Pedapati EV, et al. A resting EEG study of neocortical hyperexcitability and altered functional connectivity in fragile X syndrome. J Neurodev Disord. 2017;9(1):11.PubMedPubMedCentralCrossRef
34.
Ethridge L, White SP, Mosconi MW, Wang J, Byerly M, Sweeney JA. Reduced habituation of auditory evoked potentials indicate cortical hyper-excitability in fragile X syndrome. Transl Psychiatry. 2016;6(4):e787.PubMedPubMedCentralCrossRef
35.
Hessl D, Rivera S, Koldewyn K, Cordeiro L, Adams J, Tassone F, et al. Amygdala dysfunction in men with the fragile X premutation. Brain. 2006;130(2):404–16.PubMedCrossRef
36.
Kim S-Y, Burris J, Bassal F, Koldewyn K, Chattarji S, Tassone F, et al. Fear-specific amygdala function in children and adolescents on the fragile x spectrum: a dosage response of the FMR1 gene. Cereb Cortex. 2012;24(3):600–13.PubMedPubMedCentralCrossRef
37.
Hessl D, Wang JM, Schneider A, Koldewyn K, Le L, Iwahashi C, et al. Decreased fragile X mental retardation protein expression underlies amygdala dysfunction in carriers of the fragile X premutation. Biol Psychiatry. 2011;70(9):859–65.PubMedPubMedCentralCrossRef
38.
Holsen LM, Dalton KM, Johnstone T, Davidson RJ. Prefrontal social cognition network dysfunction underlying face encoding and social anxiety in fragile X syndrome. NeuroImage. 2008;43(3):592–604.PubMedPubMedCentralCrossRef
39.
Gale HR. Stanford Binet intelligence scales. Fifth edition. Itasca: Riverside Pub; 2003.
40.
Esbensen AJ, Rojahn J, Aman MG, Ruedrich S. Reliability and validity of an assessment instrument for anxiety, depression, and mood among individuals with mental retardation. J Autism Dev Disord. 2003;33(6):617–29.PubMedCrossRef
41.
Aman MG, Singh NN, Stewart AW, Field CJ. The aberrant behavior checklist: a behavior rating scale for the assessment of treatment effects. Am J Ment Defic. 1985;89(5):485-491.
42.
Rutter M, Bailey A, Lord C. The social communication questionnaire: manual. Los Angeles: Western Psychological Services; 2003.
43.
Sparrow SS, Cicchetti DV, Balla DA. Vineland Adaptive Behavior Scales. 2nd ed. Minneapolis: Pearson Assessments; 2005.
44.
Sansone SM, Widaman KF, Hall SS, Reiss AL, Lightbody A, Kaufmann WE, et al. Psychometric study of the aberrant behavior checklist in fragile X syndrome and implications for targeted treatment. J Autism Dev Disord. 2012;42(7):1377–92.PubMedPubMedCentralCrossRef
45.
Moriuchi JM, Klin A, Jones W. Mechanisms of diminished attention to eyes in autism. Am J Psychiatr. 2016;174(1):26–35.PubMedCrossRef
46.
Pierce K, Conant D, Hazin R, Stoner R, Desmond J. Preference for geometric patterns early in life as a risk factor for autism. Arch Gen Psychiatry. 2011;68(1):101–9.PubMedCrossRef
47.
Feinstein C, Reiss AL. Autism: the point of view from fragile X studies. J Autism Dev Disord. 1998;28(5):393–405.PubMedCrossRef
48.
Bailey DB, Hatton DD, Mesibov G, Ament N, Skinner M. Early development, temperament, and functional impairment in autism and fragile X syndrome. J Autism Dev Disord. 2000;30(1):49–59.PubMedCrossRef
49.
Hatton DD, Sideris J, Skinner M, Mankowski J, Bailey DB, Roberts J, et al. Autistic behavior in children with fragile X syndrome: prevalence, stability, and the impact of FMRP. Am J Med Genet A. 2006;140(17):1804–13.CrossRef
50.
Kaufmann WE, Cortell R, Kau AS, Bukelis I, Tierney E, Gray RM, et al. Autism spectrum disorder in fragile X syndrome: communication, social interaction, and specific behaviors. Am J Med Genet A. 2004;129(3):225–34.CrossRef
51.
Kau AS, Tierney E, Bukelis I, Stump MH, Kates WR, Trescher WH, et al. Social behavior profile in young males with fragile X syndrome: characteristics and specificity. Am J Med Genet A. 2004;126(1):9–17.CrossRef
52.
Cohen IL. Behavioral profiles of autistic and nonautistic fragile X males. Dev Brain Dys. 1995;8(4-6):252-269.
53.
Wieser MJ, Pauli P, Weyers P, Alpers GW, Mühlberger A. Fear of negative evaluation and the hypervigilance-avoidance hypothesis: an eye-tracking study. J Neural Transm. 2009;116(6):717–23.PubMedCrossRef
54.
Terburg D, Aarts H, van Honk J. Memory and attention for social threat: anxious hypercoding-avoidance and submissive gaze aversion. Emotion. 2012;12(4):666.PubMedCrossRef
55.
Bögels SM, Mansell W. Attention processes in the maintenance and treatment of social phobia: hypervigilance, avoidance and self-focused attention. Clin Psychol Rev. 2004;24(7):827–56.PubMedCrossRef
56.
Hall SS, Maynes NP, Reiss AL. Using percentile schedules to increase eye contact in children with fragile X syndrome. J Appl Behav Anal. 2009;42(1):171–6.PubMedPubMedCentralCrossRef
57.
Hall SS, Lightbody AA, McCarthy BE, Parker KJ, Reiss AL. Effects of intranasal oxytocin on social anxiety in males with fragile X syndrome. Psychoneuroendocrinology. 2012;37(4):509–18.PubMedCrossRef
Metadata
Title
Differentiating social preference and social anxiety phenotypes in fragile X syndrome using an eye gaze analysis: a pilot study
Authors
Michael P. Hong
Eleanor M. Eckert
Ernest V. Pedapati
Rebecca C. Shaffer
Kelli C. Dominick
Logan K. Wink
John A. Sweeney
Craig A. Erickson
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Journal of Neurodevelopmental Disorders / Issue 1/2019
Print ISSN: 1866-1947
Electronic ISSN: 1866-1955
DOI
https://doi.org/10.1186/s11689-019-9262-4

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