Journal of Autism and Developmental Disorders

, Volume 47, Issue 12, pp 3741–3755 | Cite as

Stranger Fear and Early Risk for Social Anxiety in Preschoolers with Fragile X Syndrome Contrasted to Autism Spectrum Disorder

  • Jessica F. Scherr
  • Abigail L. Hogan
  • Deborah Hatton
  • Jane E. RobertsEmail author
S.I. : Anxiety in Autism Spectrum Disorders


This study investigated behavioral indicators of social fear in preschool boys with fragile X syndrome (FXS) with a low degree of autism spectrum disorder (ASD) symptoms (FXS-Low; n = 29), FXS with elevated ASD symptoms (FXS-High; n = 25), idiopathic ASD (iASD; n = 11), and typical development (TD; n = 36). Gaze avoidance, escape behaviors, and facial fear during a stranger approach were coded. Boys with elevated ASD symptoms displayed more avoidant gaze, looking less at the stranger and parent than those with low ASD symptoms across etiologies. The iASD group displayed more facial fear than the other groups. Results suggest etiologically distinct behavioral patterns of social fear in preschoolers with elevated ASD symptoms.


Fragile X syndrome Autism spectrum disorder Stranger fear Anxiety Temperament 



The authors are thankful to the families who participated in this research. This project was funded by the National Institute of Mental Health (R01MH107573; R01MH0901194; PI: Roberts) and the National Institute of Child Health and Human Development (P30-HD003110-35S1; PI: Bailey).

Author contributions

JS conceived of the study, participated in its design and coordination, performed some statistical analysis, and drafted the manuscript; AH helped to draft the manuscript and performed some statistical analysis. JR participated in the design and interpretation of the data; and DH participated in the design and coordination of the study and performed the measurement. All authors read and approved the final manuscript.

Compliance with Ethical Standards

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.


  1. Abrahams, B. S., & Geschwind, D. H. (2008). Advances in autism genetics: On the threshold of a new neurobiology. Nature Reviews Genetics, 9(5), 341–355.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Achenbach, T.M., & Rescorla, L.A. (2001). Manual for the ASEBA school-age forms & profiles. Burlington, VT: University of Vermont, Research Center for Children, Youth, & Families.Google Scholar
  3. American Psychiatric Association. (2013). DSM 5. American Psychiatric Association.Google Scholar
  4. Bailey, A., Phillips, W., & Rutter, M. (1996). Autism: Towards an integration of clinical, genetic, neuropsychological, and neurobiological perspectives. Journal of Child Psychology and Psychiatry, 37(1), 89–126.PubMedCrossRefGoogle Scholar
  5. Bailey, D. B. Jr., Hatton, D. D., Skinner, M., & Mesibov, G. (2001). Autistic behavior, FMR1 protein, and developmental trajectories in young males with fragile X syndrome. Journal of Autism and Developmental Disorders, 31(2), 165–174.PubMedCrossRefGoogle Scholar
  6. Bailey, D. B., Raspa, M., Olmsted, M., & Holiday, D. B. (2008). Co - occurring conditions associated with FMR1 gene variations: Findings from a national parent survey. American Journal of Medical Genetics Part A, 146(16), 2060–2069.CrossRefGoogle Scholar
  7. Baio, J. (2012). Prevalence of autism spectrum disorders: Autism and developmental disabilities monitoring network, 14 sites, United States, 2008. Morbidity and Mortality Weekly Report. Surveillance Summaries (Vol 61, Number 3). Centers for Disease Control and Prevention.Google Scholar
  8. Baron-Cohen, S., Ring, H. A., Bullmore, E. T., Wheelwright, S., Ashwin, C., & Williams, S. C. R. (2000). The amygdala theory of autism. Neuroscience & Biobehavioral Reviews, 24(3), 355–364.CrossRefGoogle Scholar
  9. Beesdo, K., Bittner, A., Pine, D. S., Stein, M. B., Höfler, M., Lieb, R., & Wittchen, H. U. (2007). Incidence of social anxiety disorder and the consistent risk for secondary depression in the first three decades of life. Archives of General Psychiatry, 64(8), 903–912.PubMedCrossRefGoogle Scholar
  10. Bennetto, L., Taylor, A. K., Pennington, B. F., Porter, D., & Hagerman, R. J. (2001). Profile of cognitive functioning in women with the fragile X mutation. Neuropsychology, 15(2), 290.PubMedCrossRefGoogle Scholar
  11. Berry, K. J., & Mielke, P. W. (1988). A generalization of Cohen’s kappa agreement measure to interval measurement and multiple raters. Educational and Psychological Measurement, 48(4), 921–933.CrossRefGoogle Scholar
  12. Brooker, R. J., Buss, K. A., Lemery-Chalfant, K., Aksan, N., Davidson, R. J., & Goldsmith, H. H. (2013). The development of stranger fear in infancy and toddlerhood: Normative development, individual differences, antecedents, and outcomes. Developmental Science, 16(6), 864–878.PubMedPubMedCentralGoogle Scholar
  13. Budimirovic, D. B., Bukelis, I., Cox, C., Gray, R. M., Tierney, E., & Kaufmann, W. E. (2006). Autism spectrum disorder in Fragile X syndrome: Differential contribution of adaptive socialization and social withdrawal. American Journal of Medical Genetics Part A, 140(17), 1814–1826.CrossRefGoogle Scholar
  14. Cassady, J. C., & Johnson, R. E. (2002). Cognitive test anxiety and academic performance. Contemporary Educational Psychology, 27(2), 270–295.CrossRefGoogle Scholar
  15. Cath, D. C., Ran, N., Smit, J. H., van Balkom, A. J., & Comijs, H. C. (2007). Symptom overlap between autism spectrum disorder, generalized social anxiety disorder and obsessive-compulsive disorder in adults: A preliminary case-controlled study. Psychopathology, 41(2), 101–110.PubMedCrossRefGoogle Scholar
  16. Centers for Disease Control and Prevention. (2014). Prevalence of autism spectrum disorders among children aged 8 years: Autism and developmental disabilities monitoring network. MMWR Surveillance Summaries, 63(2), 1–22.Google Scholar
  17. Cervantes, P., Matson, J. L., Tureck, K., & Adams, H. L. (2013). The relationship of comorbid anxiety symptom severity and challenging behaviors in infants and toddlers with autism spectrum disorder. Research in Autism Spectrum Disorders, 7(12), 1528–1534.CrossRefGoogle Scholar
  18. Chavira, D. A., Stein, M. B., Bailey, K., & Stein, M. T. (2004). Child anxiety in primary care: Prevalent but untreated. Depression and Anxiety, 20(4), 155–164.PubMedCrossRefGoogle Scholar
  19. Clark, L. A., & Watson, D. (1999). Temperament: A new paradigm for trait psychology. Handbook of Personality: Theory and Research, 2, 399–423.Google Scholar
  20. Clark, L. A., Watson, D., & Mineka, S. (1994). Temperament, personality, and the mood and anxiety disorders. Journal of Abnormal Psychology, 103(1), 103.PubMedCrossRefGoogle Scholar
  21. Cohen, D., Pichard, N., Tordjman, S., Baumann, C., Burglen, L., Excoffier, E., Lazar, G., Mazet, P., Pinquier, C., Verloes, A., & Héron, D. (2005). Specific genetic disorders and autism: clinical contribution towards their identification. Journal of Autism and Developmental Disorders, 35(1), 103–116.PubMedCrossRefGoogle Scholar
  22. Colonnesi, C., Napoleone, E., & Bögels, S. M. (2014). Positive and negative expressions of shyness in toddlers: Are they related to anxiety in the same way. Journal of Personality and Social Psychology, 106(4), 624.PubMedCrossRefGoogle Scholar
  23. Cordeiro, L., Ballinger, E., Hagerman, R., & Hessl, D. (2010). Clinical assessment of DSM-IV anxiety disorders in fragile X syndrome: Prevalence and characterization. Journal of Neurodevelopmental Disorders, 3(1), 57–67.PubMedPubMedCentralCrossRefGoogle Scholar
  24. Cornish, K., Cole, V., Longhi, E., Karmiloff-Smith, A., & Scerif, G. (2013). Do behavioural inattention and hyperactivity exacerbate cognitive difficulties associated with autistic symptoms? Longitudinal profiles in fragile X syndrome. International Journal of Developmental Disabilities, 59(2), 80–94.CrossRefGoogle Scholar
  25. Crawford, D. C., Acuña, J. M., & Sherman, S. L. (2001). FMR1 and the fragile X syndrome: Human genome epidemiology review. Genetics in Medicine, 3(5), 359–371.PubMedPubMedCentralCrossRefGoogle Scholar
  26. Crawford, D. C., Meadows, K. L., Newman, J. L., Taft, L. F., Scott, E., Leslie, M., Shubek, L., Holmgreen, P., Yeargin-Allsopp, M., Boyle, C., & Sherman, S. L., et al. (2002). Prevalence of the fragile X syndrome in African - Americans. American Journal of Medical Genetics, 110(3), 226–233.PubMedCrossRefGoogle Scholar
  27. Davis, T. E. III, Hess, J. A., Moree, B. N., Fodstad, J. C., Dempsey, T., Jenkins, W. S., & Matson, J. L. (2011). Anxiety symptoms across the lifespan in people diagnosed with Autistic Disorder. Research in Autism Spectrum Disorders, 5(1), 112–118.CrossRefGoogle Scholar
  28. Durbin, C. E., Klein, D. N., Hayden, E. P., Buckley, M. E., & Moerk, K. C. (2005). Temperamental emotionality in preschoolers and parental mood disorders. Journal of Abnormal Psychology, 114(1), 28.PubMedCrossRefGoogle Scholar
  29. Dykens, E. M., & Volkmar, F. R. (1997). Medical conditions associated with autism. Handbook of Autism and Pervasive Developmental Disorders, 2, 388–407.Google Scholar
  30. Gagne, J. R., Van Hulle, C. A., Aksan, N., Essex, M. J., & Goldsmith, H. H. (2011). Deriving childhood temperament measures from emotion-eliciting behavioral episodes: Scale construction and initial validation. Psychological Assessment, 23(2), 337–353.Google Scholar
  31. Geschwind, D. H. (2011). Genetics of autism spectrum disorders. Trends in Cognitive Sciences, 15(9), 409–416.PubMedPubMedCentralCrossRefGoogle Scholar
  32. Goldsmith, H., & Rothbart, M. K. (1996). Prelocomotor and locomotor laboratory temperament assessment battery (Lab-TAB; version 3.0, technical manual). Madison: University of Wisconsin, Department of Psychology.Google Scholar
  33. Grant, B. F., Hasin, D. S., Blanco, C., Stinson, F. S., Chou, S. P., Goldstein, R. B., Dawson, D. A., Smith, S., Saha, T. D., & Huang, B. (2005). The epidemiology of social anxiety disorder in the United States: results from the National epidemiologic survey on alcohol and related conditions. The Journal of Clinical Psychiatry, 66(11), 1351–1361.PubMedCrossRefGoogle Scholar
  34. Gurrieri, F., & Neri, G. (2009). Defective oxytocin function: A clue to understanding the cause of autism? BMC Medicine, 7(1), 63.PubMedPubMedCentralCrossRefGoogle Scholar
  35. Hagerman, P. J. (2008). The fragile X prevalence paradox. Journal of Medical Genetics, 45(8), 498–499.PubMedPubMedCentralCrossRefGoogle Scholar
  36. Hall, S., DeBernardis, M., & Reiss, A. (2006). Social escape behaviors in children with fragile X syndrome. Journal of Autism and Developmental Disorders, 36(7), 935–947.PubMedCrossRefGoogle Scholar
  37. Hall, S. S., Lightbody, A. A., & Reiss, A. L. (2008). Compulsive, self-injurious, and autistic behavior in children and adolescents with fragile X syndrome. American Journal on Mental Retardation, 113(1), 44–53.PubMedCrossRefGoogle Scholar
  38. Harris, S. W., Hessl, D., Goodlin-Jones, B., Ferranti, J., Bacalman, S., Barbato, I. et al. (2008). Autism profiles of males with fragile X syndrome. American Journal of Mental Retardation, 113(6), 427–438.Google Scholar
  39. Izard, C. E., & Weiss, M. (1979). Maximally discriminative facial movement coding system. University of Delaware, Instructional Resources Center.Google Scholar
  40. Kagan, J., & Snidman, N. (1999). Early childhood predictors of adult anxiety disorders. Biological Psychiatry, 46(11), 1536–1541.PubMedCrossRefGoogle Scholar
  41. Kapalu, L., & Gartstein, M. A. (2016). Boys with fragile X syndrome: Investigating temperament in early childhood. Journal of Intellectual Disability Research, 60(9), 891–900.CrossRefGoogle Scholar
  42. Kaufmann, W. E., Cortell, R., Kau, A. S., Bukelis, I., Tierney, E., Gray, R. M., Cox, C., Capone, G. T., & Stanard, P. (2004). Autism spectrum disorder in fragile X syndrome: Communication, social interaction, and specific behaviors. American Journal of Medical Genetics Part A, 129(3), 225–234.CrossRefGoogle Scholar
  43. Keith, T. Z. (2015). Multiple regression and beyond: An introduction to multiple regression and structural equation modeling (2nd ed.). New York, NY: Routledge.Google Scholar
  44. Kindt, M., Bögels, S., & Morren, M. (2003). Processing bias in children with separation anxiety disorder, social phobia and generalised anxiety disorder. Behaviour Change, 20(03), 143–150.CrossRefGoogle Scholar
  45. Kreiser, N. L., & White, S. W. (2014). Assessment of social anxiety in children and adolescents with autism spectrum disorder. Clinical Psychology, 21(1), 18–31.Google Scholar
  46. La Greca, A. M., & Lopez, N. (1998). Social anxiety among adolescents: Linkages with peer relations and friendships. Journal of Abnormal Child Psychology, 26(2), 83–94.PubMedCrossRefGoogle Scholar
  47. Lesniak-Karpiak, K., Mazzocco, M. M., & Ross, J. L. (2003). Behavioral assessment of social anxiety in females with Turner or fragile X syndrome. Journal of Autism and Developmental Disorders, 33(1), 55–67.PubMedCrossRefGoogle Scholar
  48. Lonigan, C. J., & Phillips, B. M. (2001). Temperamental influences on the development of anxiety disorders. The Developmental Psychopathology of Anxiety, 60–91Google Scholar
  49. Lonigan, C. J., Phillips, B. M., & Hooe, E. S. (2003). Relations of positive and negative affectivity to anxiety and depression in children: evidence from a latent variable longitudinal study. Journal of Consulting and Clinical Psychology, 71(3), 465.PubMedCrossRefGoogle Scholar
  50. Lopata, C., & Thomeer, M. L. (2014). Autism and anxiety in school. In Handbook of autism and anxiety (pp. 201–214). New York: Springer.Google Scholar
  51. Lopata, C., Toomey, J. A., Fox, J. D., Volker, M. A., Chow, S. Y., Thomeer, M. L., et al. (2010). Anxiety and depression in children with HFASDs: Symptom levels and source differences. Journal of Abnormal Child Psychology, 38, 765–776.PubMedCrossRefGoogle Scholar
  52. Lord, C., Risi, S., Lambrecht, L., Cook, E. H. Jr., Leventhal, B. L., DiLavore, P. C., Pickles, A., & Rutter, M. (2000). The autism diagnostic observation schedule—Generic: A standard measure of social and communication deficits associated with the spectrum of autism. Journal of Autism and Developmental Disorders, 30(3), 205–223.PubMedCrossRefGoogle Scholar
  53. Lord, C., Rutter, M., DiLavore, P., Risi, S., Gotham, K., & Bishop, S. (2012). Autism diagnostic observation schedule–2nd edition (ADOS-2). Los Angeles, CA: Western Psychological Corporation.Google Scholar
  54. Mogg, K., Bradley, B. P., De Bono, J., & Painter, M. (1997). Time course of attentional bias for threat information in non-clinical anxiety. Behaviour Research and Therapy, 35(4), 297–303.PubMedCrossRefGoogle Scholar
  55. Mullen, E. M. (1995). Mullen scales of early learning. Circle Pines: American Guidance Services.Google Scholar
  56. Muris, P., Steerneman, P., Merckelbach, H., Holdrinet, I., & Meesters, C. (1998). Comorbid anxiety symptoms in children with pervasive developmental disorders. Journal of Anxiety Disorders, 12(4), 387–393.PubMedCrossRefGoogle Scholar
  57. Pisula, E. (2004). Response of children with autism to a brief separation from the mother. Polish Psychological Bulletin, 35(2), 109–115.Google Scholar
  58. Rapee, R. M. (2002). The development and modification of temperamental risk for anxiety disorders: Prevention of a lifetime of anxiety? Biological Psychiatry, 52(10), 947–957.PubMedCrossRefGoogle Scholar
  59. Rapee, R. M. (2014). Preschool environment and temperament as predictors of social and nonsocial anxiety disorders in middle adolescence. Journal of the American Academy of Child & Adolescent Psychiatry, 53(3), 320–328.CrossRefGoogle Scholar
  60. Rapee, R. M., & Coplan, R. J. (2010). Conceptual relations between anxiety disorder and fearful temperament. New Directions for Child and Adolescent Development, 2010(127), 17–31.PubMedCrossRefGoogle Scholar
  61. Rellini, E., Tortolani, D., Trillo, S., Carbone, S., & Montecchi, F. (2004). Childhood autism rating scale (CARS) and autism behavior checklist (ABC) correspondence and conflicts with DSM-IV criteria in diagnosis of autism. Journal of Autism and Developmental Disorders, 34(6), 703–708.PubMedCrossRefGoogle Scholar
  62. Roberts, J. E., Tonnsen, B. L., Robinson, M., McQuillin, S. D., & Hatton, D. D. (2014). Temperament factor structure in fragile X syndrome: The children’s behavior questionnaire. Research in Developmental Disabilities, 35(2), 563–571.PubMedCrossRefGoogle Scholar
  63. Roberts, J. E., Weisenfeld, L. A. H., Hatton, D. D., Heath, M., & Kaufmann, W. E. (2007). Social approach and autistic behavior in children with fragile X syndrome. Journal of Autism and Developmental Disorders, 37(9), 1748–1760.PubMedCrossRefGoogle Scholar
  64. Rogers, S. J., Wehner, E. A., & Hagerman, R. (2001). The behavioral phenotype in fragile X: Symptoms of autism in very young children with fragile X syndrome, idiopathic autism, and other developmental disorders. Journal of Developmental & Behavioral Pediatrics, 22(6), 409–417.CrossRefGoogle Scholar
  65. Rothbart, M. K., Ahadi, S. A., & Evans, D. E. (2000). Temperament and personality: Origins and outcomes. Journal of Personality and Social Psychology, 78(1), 122.PubMedCrossRefGoogle Scholar
  66. Rothbart, M. K., Ahadi, S. A., Hershey, K. L., & Fisher, P. (2001). Investigations of temperament at three to seven years: The Children’s Behavior Questionnaire. Child Development, 72(5), 1394–1408.PubMedCrossRefGoogle Scholar
  67. Rothbart, M. K., Derryberry, D., & Hershey, K. (2000). Stability of temperament in childhood: Laboratory infant assessment to parent report at seven years. Temperament and Personality Development Across the Life Span, 85–119.Google Scholar
  68. Ruscio, A. M., Brown, T. A., Chiu, W. T., Sareen, J., Stein, M. B., & Kessler, R. C. (2008). Social fears and social phobia in the USA: Results from the National Comorbidity Survey. Psychological Medicine, 38, 15–28.PubMedCrossRefGoogle Scholar
  69. Sacrey, L. A. R., Bennett, J. A., & Zwaigenbaum, L. (2015). Early infant development and intervention for autism spectrum disorder. Journal of Child Neurology, 30(14), 1921–1929.PubMedCrossRefGoogle Scholar
  70. Schopler, E., Reichler, R. J., & Renner, B. R. (1988). The Childhood Autism Rating Scale (CARS). Los Angeles, CA: Western Psychological Services.Google Scholar
  71. Shechner, T., Britton, J. C., Pérez-Edgar, K., Bar-Haim, Y., Ernst, M., Fox, N. A., Leibenluft, E., & Pine, D. S., et al. (2012). Attention biases, anxiety, and development: Toward or away from threats or rewards? Depression and Anxiety, 29(4), 282–294.PubMedCrossRefGoogle Scholar
  72. Simonoff, E., Pickles, A., Charman, T., Chandler, S., Loucas, T., & Baird, G. (2008). Psychiatric disorders in children with autism spectrum disorders: Prevalence, comorbidity, and associated factors in a population-derived sample. Journal of the American Academy of Child & Adolescent Psychiatry, 47(8), 921–929.CrossRefGoogle Scholar
  73. Stein, M. B., & Stein, D. J. (2008). Social anxiety disorder. Lancet, 371(9618), 1115–1125.PubMedCrossRefGoogle Scholar
  74. Strang, J. F., Kenworthy, L., Daniolos, P., Case, L., Wills, M. C., Martin, A., & Wallace, G. L. (2012). Depression and anxiety symptoms in children and adolescents with autism spectrum disorders without intellectual disability. Research in Autism Spectrum Disorders, 6(1), 406–412.PubMedPubMedCentralCrossRefGoogle Scholar
  75. Tonnsen, B. L., Malone, P. S., Hatton, D. D., & Roberts, J. E. (2013). Early negative affect predicts anxiety, not autism, in preschool boys with fragile X syndrome. Journal of Abnormal Child Psychology, 41(2), 267–280.PubMedPubMedCentralCrossRefGoogle Scholar
  76. Tonnsen, B. L., Shinkareva, S. V., Deal, S. C., Hatton, D. D., & Roberts, J. E. (2013). Biobehavioral indicators of social fear in young children with fragile X syndrome. American Journal on Intellectual and Developmental Disabilities, 118(6), 447–459.PubMedPubMedCentralCrossRefGoogle Scholar
  77. Van Steensel, F. J., Bögels, S. M., & Perrin, S. (2011). Anxiety disorders in children and adolescents with autistic spectrum disorders: A meta-analysis. Clinical Child and Family Psychology Review, 14(3), 302–317.PubMedPubMedCentralCrossRefGoogle Scholar
  78. Vasa, R. A., Kalb, L., Mazurek, M., Kanne, S., Freedman, B., Keefer, A., Clemons, T., & Murray, D. (2013). Age-related differences in the prevalence and correlates of anxiety in youth with autism spectrum disorders. Research in Autism Spectrum Disorders, 7(11), 1358–1369.CrossRefGoogle Scholar
  79. Wheeler, A., Raspa, M., Bann, C., Bishop, E., Hessl, D., Sacco, P., & Bailey, D. B. (2014). Anxiety, attention problems, hyperactivity, and the Aberrant Behavior Checklist in fragile X syndrome. American Journal of Medical Genetics Part A, 164(1), 141–155.CrossRefGoogle Scholar
  80. White, S. W., Oswald, D., Ollendick, T., & Scahill, L. (2009). Anxiety in children and adolescents with autism spectrum disorders. Clinical Psychology Review, 29(3), 216–229.PubMedPubMedCentralCrossRefGoogle Scholar
  81. Williams, T. A., Porter, M. A., & Langdon, R. (2014). Social approach and emotion recognition in fragile X syndrome. American Journal on Intellectual and Developmental Disabilities, 119(2), 133–150.PubMedCrossRefGoogle Scholar
  82. Yu, T. W., & Berry-Kravis, E. (2014). Autism and fragile x syndrome. Seminars in Neurology, 34(3), 258–265.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Jessica F. Scherr
    • 1
  • Abigail L. Hogan
    • 1
  • Deborah Hatton
    • 2
  • Jane E. Roberts
    • 1
    Email author
  1. 1.Department of PsychologyUniversity of South CarolinaColumbiaUSA
  2. 2.Department of Special EducationVanderbilt UniversityNashvilleUSA

Personalised recommendations