Hostname: page-component-cb9f654ff-pvkqz Total loading time: 0 Render date: 2025-09-06T05:24:51.818Z Has data issue: false hasContentIssue false
  • English
  • Français

Genetic architecture of reciprocal social behavior in toddlers: Implications for heterogeneity in the early origins of autism spectrum disorder

Published online by Cambridge University Press:  09 November 2020

Natasha Marrus ,
Julia D. Grant ,
Brooke Harris-Olenak ,
Jordan Albright ,
Drew Bolster ,
Jon Randolph Haber ,
Theodore Jacob ,
Yi Zhang ,
Andrew C. Heath  and
Arpana Agrawal
...Show all authors
Natasha Marrus*
Affiliation:
Department of Psychiatry, Washington University, St. Louis, MO, USA
Julia D. Grant
Affiliation:
Department of Psychiatry, Washington University, St. Louis, MO, USA Department of Psychology, Maryville University of St. Louis, St. Louis, MO, USA
Brooke Harris-Olenak
Affiliation:
Kaiser Permanente San Jose, San Jose, CA, USA
Jordan Albright
Affiliation:
Department of Psychiatry, Washington University, St. Louis, MO, USA
Drew Bolster
Affiliation:
Department of Psychiatry, Washington University, St. Louis, MO, USA
Jon Randolph Haber
Affiliation:
Palo Alto Veterans Affairs Health Care System, Menlo Park, CA, USA
Theodore Jacob
Affiliation:
Palo Alto Veterans Affairs Health Care System, Menlo Park, CA, USA
Yi Zhang
Affiliation:
Department of Psychiatry, Washington University, St. Louis, MO, USA
Andrew C. Heath
Affiliation:
Department of Psychiatry, Washington University, St. Louis, MO, USA
Arpana Agrawal
Affiliation:
Department of Psychiatry, Washington University, St. Louis, MO, USA
John N. Constantino
Affiliation:
Department of Psychiatry, Washington University, St. Louis, MO, USA
Jed T. Elison
Affiliation:
Institute of Child Development, University of Minnesota, Minneapolis, MN, USA Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA
Anne L. Glowinski
Affiliation:
Department of Psychiatry, Washington University, St. Louis, MO, USA
*
Author for Correspondence: Natasha Marrus, MD, PhD, Department of Psychiatry, Division of Child and Adolescent Psychiatry, Washington University School of Medicine, 660 South Euclid, Box 8504, St. Louis, MO 63110, USA; E-mail: natasha@wustl.edu
Get access Rights & Permissions [Opens in a new window]

Abstract

Impairment in reciprocal social behavior (RSB), an essential component of early social competence, clinically defines autism spectrum disorder (ASD). However, the behavioral and genetic architecture of RSB in toddlerhood, when ASD first emerges, has not been fully characterized. We analyzed data from a quantitative video-referenced rating of RSB (vrRSB) in two toddler samples: a community-based volunteer research registry (n = 1,563) and an ethnically diverse, longitudinal twin sample ascertained from two state birth registries (n = 714). Variation in RSB was continuously distributed, temporally stable, significantly associated with ASD risk at age 18 months, and only modestly explained by sociodemographic and medical factors (r2 = 9.4%). Five latent RSB factors were identified and corresponded to aspects of social communication or restricted repetitive behaviors, the two core ASD symptom domains. Quantitative genetic analyses indicated substantial heritability for all factors at age 24 months (h2 ≥ .61). Genetic influences strongly overlapped across all factors, with a social motivation factor showing evidence of newly-emerging genetic influences between the ages of 18 and 24 months. RSB constitutes a heritable, trait-like competency whose factorial and genetic structure is generalized across diverse populations, demonstrating its role as an early, enduring dimension of inherited variation in human social behavior. Substantially overlapping RSB domains, measurable when core ASD features arise and consolidate, may serve as markers of specific pathways to autism and anchors to inform determinants of autism's heterogeneity.

Keywords

quantitative autistic traitsreciprocal social behaviortoddlerstwinsvrRSB

Information

Type
Special Section Articles
Information
Development and Psychopathology , Volume 32 , Special Issue 4: Conceptualizing and Interrogating Autism Spectrum Disorder from a Developmental Psychopathology Framework , October 2020 , pp. 1190 - 1205
Check for updates
Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

Footnotes

†

Deceased August 22, 2016

*

Senior authors who contributed equally to the development of this manuscript

References

American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (DSM-5) (5th ed.). Washington, DC: Author.Google Scholar
Bai, D., Yip, B. H. K., Windham, G. C., Sourander, A., Francis, R., Yoffe, R., … Gissler, M. (2019). Association of genetic and environmental factors with autism in a 5-country cohort. JAMA Psychiatry, 76, 1035–1043. doi:10.1001/jamapsychiatry.2019.1411CrossRefGoogle Scholar
Beuker, K. T., Schjølberg, S., Lie, K. K., Donders, R., Lappenschaar, M., Swinkels, S. H., & Buitelaar, J. K. (2013). The structure of autism spectrum disorder symptoms in the general population at 18 months. Journal of Autism and Developmental Disorders, 43, 45–56. doi:10.1007/s10803-012-1546-4CrossRefGoogle ScholarPubMed
Bing, M. N., Whanger, J. C., Davison, H. K., & VanHook, J. B. (2004). Incremental validity of the frame-of-reference effect in personality scale scores: a replication and extension. Journal of Applied Psychology, 89, 150. doi:10.1037/0021-9010.89.1.150CrossRefGoogle Scholar
Boomsma, A., Van Lang, N. D. J., De Jonge, M. V., De Bildt, A. A., Van Engeland, H., & Minderaa, R. B. (2008). A new symptom model for autism cross-validated in an independent sample. Journal of Child Psychology and Psychiatry, 49, 809–816. doi:10.1111/j.1469-7610.2008.01897.xCrossRefGoogle Scholar
Bucholz, K. K., Cadoret, R., Cloninger, C. R., Dinwiddie, S. H., Hesselbrock, V. M., Nurnberger, J. I., … Schuckit, M. A. (1994). A new, semi-structured psychiatric interview for use in genetic linkage studies: A report on the reliability of the SSAGA. Journal of Studies on Alcohol and Drugs, 55, 149–158. doi:10.15288/jsa.1994.55.149CrossRefGoogle ScholarPubMed
Castelbaum, L., Sylvester, C. M., Zhang, Y., Qiongry, Y., & Constantino, J. N. (2019). On the nature of monozygotic twin concordance for autistic trait severity: A quantitative analysis. Behavior Genetics, 1–10. doi:10.1007/s10519-019-09987-2Google ScholarPubMed
Cen, C. Q., Liang, Y. Y., Chen, Q. R., Chen, K. Y., Deng, H. Z., Chen, B. Y., & Zou, X. B. (2017). Investigating the validation of the Chinese Mandarin version of the social responsiveness scale in a mainland China child population. BMC Psychiatry, 17, 51. doi:10.1186/s12888-016-1185-yCrossRefGoogle Scholar
Cheon, K. A., Park, J. I., Koh, Y. J., Song, J., Hong, H. J., Kim, Y. K., … Paik, K. C. (2016). The social responsiveness scale in relation to DSM IV and DSM 5 ASD in Korean children. Autism Research, 9, 970–980. doi:10.1002/aur.1671CrossRefGoogle ScholarPubMed
Chevallier, C., Kohls, G., Troiani, V., Brodkin, E. S., & Schultz, R. T. (2012). The social motivation theory of autism. Trends in Cognitive Sciences, 16, 231–239. doi:10.1016/j.tics.2012.02.007CrossRefGoogle ScholarPubMed
Cicchetti, D. (1984). The emergence of developmental psychopathology. Child Development, 55, 1–7. doi:10.2307/1129830CrossRefGoogle ScholarPubMed
Cicchetti, D. (1993). Developmental psychopathology: Reactions, reflections, projections. Developmental Review, 13, 471–502. doi:10.1006/drev.1993.1021CrossRefGoogle Scholar
Constantino, J. N. (2018). Deconstructing autism: from unitary syndrome to contributory developmental endophenotypes. International Review of Psychiatry, 30, 18–24. doi:10.1080/09540261.2018.1433133CrossRefGoogle ScholarPubMed
Constantino, J. N. (2019). Early behavioral indices of inherited liability to autism. Pediatric Research, 85, 127–133. doi:10.1038/s41390-018-0217-3CrossRefGoogle ScholarPubMed
Constantino, J. N., & Gruber, C. P. (2012). Social responsiveness Scale (SRS-2) (2nd ed.) Torrance, CA: Western Psychological Services.Google Scholar
Constantino, J. N., Gruber, C. P., Davis, S., Hayes, S., Passanante, N., & Przybeck, T. (2004). The factor structure of autistic traits. Journal of Child Psychology and Psychiatry, 45, 719–726. doi:10.1111/j.1469-7610.2004.00266.xCrossRefGoogle ScholarPubMed
Constantino, J. N., Hudziak, J. J., & Todd, R. D. (2003). Deficits in reciprocal social behavior in male twins: evidence for a genetically independent domain of psychopathology. Journal of the American Academy of Child & Adolescent Psychiatry, 42, 458–467. doi:10.1097/01.CHI.0000046811.95464.21CrossRefGoogle ScholarPubMed
Constantino, J. N., & Todd, R. D. (2003). Autistic traits in the general population: a twin study. Archives of General Psychiatry, 60, 524–530. doi:10.1001/archpsyc.60.5.524CrossRefGoogle ScholarPubMed
Duku, E., Vaillancourt, T., Szatmari, P., Georgiades, S., Zwaigenbaum, L., Smith, I. M., … The Pathways in ASD Study Team (2013). Investigating the measurement properties of the social responsiveness scale in preschool children with autism spectrum disorders. Journal of Autism and Developmental Disorders, 43, 860–868. doi:10.1007/s10803-012-1627-4CrossRefGoogle ScholarPubMed
Estes, A., Zwaigenbaum, L., Gu, H., St. John, T., Paterson, S., Elison, J. T., … the Pathways in ASD Study Team (2015). Behavioral, cognitive, and adaptive development in infants with autism spectrum disorder in the first 2 years of life. Journal of Neurodevelopmental Disorders, 7, 24. doi:10.1186/s11689-015-9117-6CrossRefGoogle ScholarPubMed
Evans, G. W., & English, K. (2002). The environment of poverty: Multiple stressor exposure, psychophysiological stress, and socioemotional adjustment. Child Development, 73, 1238–1248. doi:10.1111/1467-8624.00469CrossRefGoogle ScholarPubMed
Frazier, T. W., Ratliff, K. R., Gruber, C., Zhang, Y., Law, P. A., & Constantino, J. N. (2014). Confirmatory factor analytic structure and measurement invariance of quantitative autistic traits measured by the Social Responsiveness Scale-2. Autism, 18, 31–44. doi:10.1177/1362361313500382CrossRefGoogle ScholarPubMed
Frazier, T. W., Youngstrom, E. A., Kubu, C. S., Sinclair, L., & Rezai, A. (2008). Exploratory and confirmatory factor analysis of the autism diagnostic interview-revised. Journal of Autism and Developmental Disorders, 38, 474–480. doi:10.1007/s10803-007-0415-zCrossRefGoogle ScholarPubMed
Hawks, Z. W., Marrus, N., Glowinski, A. L., & Constantino, J. N. (2019). Early origins of autism comorbidity: Neuropsychiatric traits correlated in childhood are independent in infancy. Journal of Abnormal Child Psychology, 47, 369–379. doi:10.1007/s10802-018-0410-1CrossRefGoogle ScholarPubMed
Hediger, M. L., Overpeck, M. D., Ruan, W. J., & Troendle, J. F. (2002). Birthweight and gestational age effects on motor and social development. Paediatric and Perinatal Epidemiology, 16, 33–46. doi:10.1046/j.1365-3016.2002.00393.xCrossRefGoogle ScholarPubMed
Hernandez, D. J. (1997). Child development and the social demography of childhood. Child Development, 68, 149–169. doi:10.2307/1131933CrossRefGoogle Scholar
Hu, L. T., & Bentler, P. M. (1999). Cutoff criteria for fit indexes in covariance structure analysis: Conventional criteria versus new alternatives. Structural Equation Modeling: A Multidisciplinary Journal, 6, 1–55. doi:10.1080/10705519909540118CrossRefGoogle Scholar
Jennrich, R. I., & Sampson, P. F. (1966). Rotation for simple loadings. Psychometrika, 31, 313–323. doi:10.1007/BF02289465CrossRefGoogle ScholarPubMed
Kamio, Y., Inada, N., Moriwaki, A., Kuroda, M., Koyama, T., Tsujii, H., … Constantino, J. N. (2013). Quantitative autistic traits ascertained in a national survey of 22 529 Japanese schoolchildren. Acta Psychiatrica Scandinavica, 128, 45–53. doi:10.1111/acps.12034CrossRefGoogle Scholar
Lam, K. S., & Aman, M. G. (2007). The Repetitive Behavior Scale-Revised: Independent validation in individuals with autism spectrum disorders. Journal of Autism and Developmental Disorders, 37, 855–866. doi:10.1007/s10803-006-0213-zCrossRefGoogle ScholarPubMed
Lam, K. S., Bodfish, J. W., & Piven, J. (2008). Evidence for three subtypes of repetitive behavior in autism that differ in familiality and association with other symptoms. Journal of Child Psychology and Psychiatry, and Allied Disciplines, 49, 1193–1200. doi:10.1111/j.1469-7610.2008.01944.xCrossRefGoogle ScholarPubMed
Landa, R. J., Gross, A. L., Stuart, E. A., & Bauman, M. (2012). Latent class analysis of early developmental trajectory in baby siblings of children with autism. Journal of Child Psychology and Psychiatry, and Allied Disciplines, 53, 986–996. doi:10.1111/j.1469-7610.2012.02558.xCrossRefGoogle ScholarPubMed
Lasch, C., Wolff, J. J., & Elison, J. T. (2019). Examining criterion-oriented validity of the repetitive behavior scales for early childhood (RBS-EC) and the video-referenced rating of reciprocal social behavior (vrRSB). Development and Psychopathology, 1–11. doi:10.1017/S0954579419001159Google Scholar
Lievens, F., De Corte, W., & Schollaert, E. (2008). A closer look at the frame-of-reference effect in personality scale scores and validity. Journal of Applied Psychology, 93, 268. doi:10.1037/0021-9010.93.2.268CrossRefGoogle Scholar
Marrus, N., Glowinski, A. L., Jacob, T., Klin, A., Jones, W., Drain, C. E., … Constantino, J. N. (2015). Rapid video-referenced ratings of reciprocal social behavior in toddlers: a twin study. Journal of Child Psychology and Psychiatry, 56, 1338–1346. doi:10.1111/jcpp.12391CrossRefGoogle ScholarPubMed
Marrus, N., Kennon-McGill, S., Harris, B., Zhang, Y., Glowinski, A. L., & Constantino, J. N. (2018). Use of a video scoring anchor for rapid serial assessment of social communication in toddlers. Journal of Visualized Experiments, 133, e57041. doi:10.3791/57041Google Scholar
McLoyd, V. C. (1998). Socioeconomic disadvantage and child development. American Psychologist, 53, 185. doi:10.1037/0003-066X.53.2.185CrossRefGoogle ScholarPubMed
Muthén, L. K., & Muthén, B. O. (2012). Mplus user's guide (7th ed.). Los Angeles, CA: Muthén & Muthén.Google Scholar
Neale, M. C. (2000). Mx: statistical modeling (2nd ed.). Richmond, VA: VCU Department of Psychiatry.Google Scholar
Neale, M. C., & Maes, H. H. M. (2004). Methodology for genetic studies of twins and families. Dordrecht: Kluwer.Google Scholar
Over, H. (2016). The origins of belonging: social motivation in infants and young children. Philosophical Transactions of the Royal Society of London. Series B, Biological sciences, 371, 20150072. doi:10.1098/rstb.2015.0072CrossRefGoogle ScholarPubMed
Pohl, A., Jones, W. R., Marrus, N., Zhang, Y., Klin, A., & Constantino, J. N. (2019). Behavioral predictors of autism recurrence are genetically independent and influence social reciprocity: Evidence that polygenic ASD risk is mediated by separable elements of developmental liability. Translational Psychiatry, 9, 202. doi:10.1038/s41398-019-0545-zCrossRefGoogle ScholarPubMed
Price, T. S., Freeman, B., Craig, I., Petrill, S. A., Ebersole, L., & Plomin, R. (2000). Infant zygosity can be assigned by parental report questionnaire data. Twin Research and Human Genetics, 3, 129–133. doi:10.1375/twin.3.3.129CrossRefGoogle ScholarPubMed
Reich, W. (2000). Diagnostic interview for children and adolescents (DICA). Journal of the American Academy of Child & Adolescent Psychiatry, 39, 59–66. doi:10.1097/00004583-200001000-00017CrossRefGoogle Scholar
Robins, D. L., Fein, D., Barton, M. L., & Green, J. A. (2001). The Modified Checklist for Autism in Toddlers: an initial study investigating the early detection of autism and pervasive developmental disorders. Journal of Autism and Developmental Disorders, 31, 131–144. doi:10.1023/A:1010738829569CrossRefGoogle ScholarPubMed
Sandin, S., Schendel, D., Magnusson, P., Hultman, C., Surén, P., Susser, E., … Henning, M. (2016). Autism risk associated with parental age and with increasing difference in age between the parents. Molecular Psychiatry, 21, 693–700. doi:10.1038/mp.2015.70CrossRefGoogle ScholarPubMed
Shuster, J., Perry, A., Bebko, J., & Toplak, M. E. (2014). Review of factor analytic studies examining symptoms of autism spectrum disorders. Journal of Autism and Developmental Disorders, 44, 90–110. doi:10.1007/s10803-013-1854-3CrossRefGoogle ScholarPubMed
Sifre, R., Lasch, C., Fenoglio, A., Georgieff, M. K., Wolff, J. J., & Elison, J. T. (2018). Restricted, repetitive, and reciprocal social behavior in toddlers born small for gestation duration. The Journal of Pediatrics, 200, 118–124. doi:10.1016/j.jpeds.2018.05.003CrossRefGoogle ScholarPubMed
Singer, E., & Ye, C. (2013). The use and effects of incentives in surveys. Annals of the American Academy of Political and Social Science, 645, 112–141. doi:10.1177/0002716212458082CrossRefGoogle Scholar
Skuse, D. H., Mandy, W., Steer, C., Miller, L. L., Goodman, R., Lawrence, K., … Golding, J. (2009). Social communication competence and functional adaptation in a general population of children: preliminary evidence for sex-by-verbal IQ differential risk. Journal of the American Academy of Child & Adolescent Psychiatry, 48, 128–137. doi:10.1097/CHI.0b013e31819176b8CrossRefGoogle Scholar
Sutcliffe, A. G., & Derom, C. (2006). Follow-up of twins: health, behaviour, speech, language outcomes and implications for parents. Early Human Development, 82, 379–86. doi:10.1016/j.earlhumdev.2006.03.007CrossRefGoogle ScholarPubMed
Takei, R., Matsuo, J., Takahashi, H., Uchiyama, T., Kunugi, H., & Kamio, Y. (2014). Verification of the utility of the social responsiveness scale for adults in non-clinical and clinical adult populations in Japan. BMC Psychiatry, 14, 302. doi:10.1186/s12888-014-0302-zCrossRefGoogle ScholarPubMed
Wagner, R. E., Zhang, Y., Gray, T., Abbacchi, A., Cormier, D., Todorov, A., & Constantino, J. N. (2019). Autism-related variation in reciprocal social behavior: A longitudinal study. Child Development, 90, 441–451. doi:10.1111/cdev.13170CrossRefGoogle ScholarPubMed
Wolff, J. J., Boyd, B. A., & Elison, J. T. (2016). A quantitative measure of restricted and repetitive behaviors for early childhood. Journal of Neurodevelopmental Disorders, 8, 27. https://goi.org/10.1186/s11689-016-9161-xCrossRefGoogle ScholarPubMed
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, 143–52. doi:10.1016/j.ijdevneu.2004.05.001CrossRefGoogle ScholarPubMed
Supplementary material: File

Marrus et al. supplementary material

Tables S1-S4

Download Marrus et al. supplementary material(File)
File 35.3 KB