Medical history of discordant twins and environmental etiologies of autism
Open accessAbstract
The environmental contributions to autism spectrum disorder (ASD) and their informative content for diagnosing the condition are still largely unknown. The objective of this study was to investigate associations between early medical events and ASD, as well as autistic traits, in twins, to test the hypothesis of a cumulative environmental effect on ASD risk. A total of 80 monozygotic (MZ) twin pairs (including a rare sample of 13 twin pairs discordant for clinical ASD) and 46 dizygotic (DZ) twin pairs with varying autistic traits, were examined for intra-pair differences in early medical events (for example, obstetric and neonatal factors, first year infections). First, differences in early medical events were investigated using multisource medical records in pairs qualitatively discordant for ASD. The significant intra-pair differences identified were then tested in relation to autistic traits in the remaining sample of 100 pairs, applying generalized estimating equations analyses. Significant association of the intra-pair differences in the MZ pairs were found for the cumulative load of early medical events and clinical ASD (Z=−2.85, P=0.004) and autistic traits (β=78.18, P=0.002), as well as infant dysregulation (feeding, sleeping abnormalities, excessive crying and worriedness), when controlling for intelligence quotient and attention deficit hyperactivity disorder comorbidity. The cumulative load of early medical events in general, and infant dysregulation in particular, may index children at risk of ASD owing to non-shared environmental contributions. In clinical practice, these findings may facilitate screening and early detection of ASD.
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A recent study showed that associations between pesticide exposures and ASD were modulated by folate intake during the first month of pregnancy, with evidence of a cumulative risk for environmental effects in autism.
“a recent study showed that associations between pesticide exposures and ASD were modulated by folate intake during the first month of pregnancy [255] with evidence of a cumulative risk for environmental effects in autism [32].”
From The contribution of environmental exposure to the etiology of autism spectrum disorder (2019) · cites this paper as [32]
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Cites
Diagnostic and Statistical Manual of Mental Disorders
American Psychiatric Association (2013) · doi:10.1176/appi.books.9780890425596 · Cited by 116,369 · see citing works
PLINK: a tool set for whole-genome association and population-based linkage analyses.
Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A. R., Bender, D., Maller, J., Sklar, P., de Bakker, P. I. W., Daly, M. J., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/519795 · Cited by 34,089 · see citing works
KAUFMAN, J., BIRMAHER, B., BRENT, D., RAO, U., FLYNN, C., MORECI, P., WILLIAMSON, D., & RYAN, N. (1997) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/00004583-199707000-00021 · Cited by 10,148 · see citing works
Cicchetti, D. V. (1994) · Psychological Assessment · doi:10.1037/1040-3590.6.4.284 · Cited by 9,349 · see citing works
Lord, C., Rutter, M., & Le Couteur, A. (1994) · Journal of Autism and Developmental Disorders · doi:10.1007/bf02172145 · Cited by 9,065 · see citing works
Peabody Picture Vocabulary Test
Campbell, J. M., & Dommestrup, A. K. (2010) · The Corsini Encyclopedia of Psychology · doi:10.1002/9780470479216.corpsy0649 · Cited by 3,787 · see citing works
Simonoff, E., Pickles, A., Charman, T., Chandler, S., Loucas, T., & Baird, G. (2008) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/chi.0b013e318179964f · Cited by 3,399 · see citing works
Lai, M.-C., Lombardo, M. V., & Baron-Cohen, S. (2014) · The Lancet · doi:10.1016/s0140-6736(13)61539-1 · Cited by 2,371 · see citing works
Genetic Heritability and Shared Environmental Factors Among Twin Pairs With Autism
Hallmayer, J. (2011) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2011.76 · Cited by 1,970 · see citing works
Constantino, J. N., Davis, S. A., Todd, R. D., Schindler, M. K., Gross, M. M., Brophy, S. L., Metzger, L. M., Shoushtari, C. S., Splinter, R., & Reich, W. (2003) · Journal of Autism and Developmental Disorders · doi:10.1023/a:1025014929212 · Cited by 1,611 · see citing works
Microbial reconstitution reverses maternal diet-induced social and synaptic deficits in offspring
Buffington, S. A., Di Prisco, G. V., Auchtung, T. A., Ajami, N. J., Petrosino, J. F., & Costa-Mattioli, M. (2016) · Cell · doi:10.1016/j.cell.2016.06.001 · Cited by 1,163 · see citing works
Sandin, S., Lichtenstein, P., Kuja-Halkola, R., Larsson, H., Hultman, C. M., & Reichenberg, A. (2014) · JAMA · doi:10.1001/jama.2014.4144 · Cited by 1,073 · see citing works
Self-citationThe Screening and Diagnosis of Autistic Spectrum Disorders
Filipek, P. A., Accardo, P., Baranek, G. T., Cook, E. H., Dawson, G., Gordon, B., Gravel, J. S., Johnson, C. P., Kallen, R. J., Levy, S. E., et al. (1999) · Journal of Autism and Developmental Disorders · doi:10.1023/a:1021943802493 · Cited by 996 · see citing works
Zwaigenbaum, L., Bauman, M. L., Choueiri, R., Kasari, C., Carter, A., Granpeesheh, D., Mailloux, Z., Smith Roley, S., Wagner, S., Fein, D., et al. (2015) · Pediatrics · doi:10.1542/peds.2014-3667e · Cited by 856 · see citing works
The genetics of autism spectrum disorders and related neuropsychiatric disorders in childhood
Lichtenstein, P., Carlström, E., Råstam, M., Gillberg, C., & Anckarsäter, H. (2010) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2010.10020223 · Cited by 738 · see citing works
Prenatal risk factors for autism: comprehensive meta-analysis
Gardener, H., Spiegelman, D., & Buka, S. L. (2009) · British Journal of Psychiatry · doi:10.1192/bjp.bp.108.051672 · Cited by 736 · see citing works
Generalized Estimating Equation Models for Correlated Data: A Review with Applications
Zorn, C. (2001) · American Journal of Political Science · doi:10.2307/2669353 · Cited by 694 · see citing works
Perinatal and Neonatal Risk Factors for Autism: A Comprehensive Meta-analysis
Gardener, H., Spiegelman, D., & Buka, S. L. (2011) · Pediatrics · doi:10.1542/peds.2010-1036 · Cited by 665 · see citing works
The NIMH research domain criteria initiative: Background, issues, and pragmatics
Kozak, M. J., & Cuthbert, B. N. (2016) · Psychophysiology · doi:10.1111/psyp.12518 · Cited by 655 · see citing works
Autism spectrum disorders and autistic traits: A decade of new twin studies
Ronald, A., & Hoekstra, R. A. (2011) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.31159 · Cited by 616 · see citing works
Self-citationHeritability of Autism Spectrum Disorder in a UK Population-Based Twin Sample
Colvert, E., Tick, B., McEwen, F., Stewart, C., Curran, S. R., Woodhouse, E., Gillan, N., Hallett, V., Lietz, S., Garnett, T., et al. (2015) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2014.3028 · Cited by 560 · see citing works
Self-citationAdaptive Behavior Assessment System
Malatino, K. W. (2018) · The SAGE Encyclopedia of Intellectual and Developmental Disorders · doi:10.4135/9781483392271.n14 · Cited by 553 · see citing works
Early Identification of Autism Spectrum Disorder: Recommendations for Practice and Research
Zwaigenbaum, L., Bauman, M. L., Stone, W. L., Yirmiya, N., Estes, A. M., Hansen, R. L., McPartland, J. C., Natowicz, M. R., Choueiri, R., FEIN, D. A., et al. (2015) · PEDIATRICS · doi:10.1542/peds.2014-3667c · Cited by 512 · see citing works
Genetic Heterogeneity Between the Three Components of the Autism Spectrum: A Twin Study
RONALD, A., HAPPÉ, F., BOLTON, P., BUTCHER, L. M., PRICE, T. S., WHEELWRIGHT, S., BARON-COHEN, S., & PLOMIN, R. (2006) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/01.chi.0000215325.13058.9d · Cited by 508 · see citing works
Self-citationAssessing autistic traits: cross‐cultural validation of the social responsiveness scale (SRS)
Bölte, S., Poustka, F., & Constantino, J. N. (2008) · Autism Research · doi:10.1002/aur.49 · Cited by 448 · see citing works
Self-citationAutism in Infancy and Early Childhood
Volkmar, F., Chawarska, K., & Klin, A. (2005) · Annual Review of Psychology · doi:10.1146/annurev.psych.56.091103.070159 · Cited by 400 · see citing works
Genetic risk for autism spectrum disorders and neuropsychiatric variation in the general population
iPSYCH-SSI-Broad Autism Group, Robinson, E. B., St Pourcain, B., Anttila, V., Kosmicki, J. A., Bulik-Sullivan, B., Grove, J., Maller, J., Samocha, K. E., Sanders, S. J., et al. (2016) · Nature Genetics · doi:10.1038/ng.3529 · Cited by 367 · see citing works
Self-citationMandy, W., & Lai, M. (2016) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.12501 · Cited by 283 · see citing works
Autism Spectrum Disorders and Epigenetics
Grafodatskaya, D., Chung, B., Szatmari, P., & Weksberg, R. (2010) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2010.05.005 · Cited by 235 · see citing works
Neuhaus, J. M., & McCulloch, C. E. (2006) · Journal of the Royal Statistical Society Series B (Statistical Methodology) · doi:10.1111/j.1467-9868.2006.00570.x · Cited by 202 · see citing works
Obstetric Complications in Autism: Consequences or Causes of the Condition?
BOLTON, P. F., MURPHY, M., MACDONALD, H., WHITLOCK, B., PICKLES, A., & RUTTER, M. (1997) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/00004583-199702000-00018 · Cited by 198 · see citing works
Charman, T., & Gotham, K. (2013) · Child and Adolescent Mental Health · doi:10.1111/j.1475-3588.2012.00664.x · Cited by 185 · see citing works
The discordant MZ-twin method: One step closer to the holy grail of causality
Vitaro, F., Brendgen, M. R., & Arseneault, L. (2009) · International Journal of Behavioral Development · doi:10.1177/0165025409340805 · Cited by 135 · see citing works
Hallmayer, J., Glasson, E., Bower, C., Petterson, B., Croen, L., Grether, J., & Risch, N. (2002) · American Journal of Human Genetics · doi:10.1086/342990 · Cited by 119 · see citing works
de Schipper, E. J., Lundequist, A., Coghill, D., de Vries, P. J., Granlund, M., Holtmann, M. H., Jonsson, U., Karande, S., Robison, J. E., Shulman, C., et al. (2015) · Autism Research · doi:10.1002/aur.1485 · Cited by 89 · see citing works
Self-citationLower birth weight indicates higher risk of autistic traits in discordant twin pairs
Losh, M. C., Esserman, D., Anckarsäter, H. S., Sullivan, P. F., & Lichtenstein, P. (2011) · Psychological Medicine · doi:10.1017/s0033291711002339 · Cited by 73 · see citing works
The Roots of Autism and ADHD Twin Study in Sweden (RATSS)
Bölte, S., Willfors, C., Berggren, S., Norberg, J., Poltrago, L., Mevel, K., Coco, C., Fransson, P., Borg, J., Sitnikov, R., et al. (2014) · Twin Research and Human Genetics · doi:10.1017/thg.2014.12 · Cited by 71 · see citing works
Self-citationAutism before diagnosis: crying, feeding and sleeping problems in the first two years of life
Olsson, M. B., Carlsson, L. H., Westerlund, J., Gillberg, C., & Fernell, E. (2013) · Acta Paediatrica · doi:10.1111/apa.12229 · Cited by 48 · see citing works
Doubly robust methods for handling confounding by cluster
Zetterqvist, J., Vansteelandt, S., Yudi Pawitan, Y., & Sjölander, A. (2015) · Biostatistics · doi:10.1093/biostatistics/kxv041 · Cited by 46 · see citing works
Santos, I. S., Matijasevich, A., Capilheira, M. F., Anselmi, L., & Barros, F. C. (2015) · Journal of Epidemiology & Community Health · doi:10.1136/jech-2014-204568 · Cited by 42 · see citing works
Ronald, A., Happé, F., Dworzynski, K., Bolton, P., & Plomin, R. (2010) · Child Development · doi:10.1111/j.1467-8624.2009.01387.x · Cited by 39 · see citing works
Self-citationGenetic risk for autism spectrum disorders and neuropsychiatric variation in the general populationPreprint
Robinson, E., Pourcain, B. S., Anttila, V., Kosmicki, J. A., Bulik-Sullivan, B. K., Grove, J., Maller, J., Samocha, K. E., Sanders, S., Ripke, S., et al. (2015) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/027771 · Cited by 34 · see citing works
Self-citationWeapon Involvement in the Victimization of Children
Mitchell, K. J., Hamby, S., Turner, H. A., et al. (2015) · PEDIATRICS · doi:10.1542/peds.2014-3966 · Cited by 30 · see citing works
No major effect of twinning on autistic traits
Curran, S. R., Dworzynski, K., Happe, F. G. E., Ronald, A., Allison, C. L., Baron‐Cohen, S., Brayne, C., & Bolton, P. (2011) · Autism Research · doi:10.1002/aur.207 · Cited by 26 · see citing works
Self-citationOn the origins of autism: The Quantitative Threshold Exposure hypothesis
Crawford, S. (2015) · Medical Hypotheses · doi:10.1016/j.mehy.2015.10.006 · Cited by 13 · see citing works
Flagged first, then by citations
Research works printed but not linked: 4
- Lord C, Rutter M, DiLavore P, Risi S, Gotham K, Bishop S. Autism Diagnostic Observation Schedule, Second Edition (ADOS-2) Manual (Part I). Western Psychological Services: Torrance, 2012.
- Kooij JJS. Diagnostic Interview for ADHD in Adults 2.0 (DIVA 2.0) Diagnostic Assessment and Treatment. Pearson Assessment and Information BV: Amsterdam, 2010.
- Wechsler D. WISC-IV Technical and Interpretive Manual. Pearson: San Antonio, TX, USA, 2003.
- Wechsler D. WAIS-IV Technical and Interpretative Manual. Pearson: San Antonio, TX, USA, 2008.
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The contribution of environmental exposure to the etiology of autism spectrum disorder
Bölte, S., Girdler, S., & Marschik, P. B. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2988-4 · Cited by 509 · see citing works
Self-citationThe association between ADHD and physical health: a co-twin control study
Pan, P.-Y., & Bölte, S. (2020) · Scientific Reports · doi:10.1038/s41598-020-78627-1 · Cited by 37 · see citing works
Self-citation
- Authors
- Willfors, C., Carlsson, T., Anderlid, B.-M., Nordgren, A., Kostrzewa, E., Berggren, S., Ronald, A., Kuja-Halkola, R., Tammimies, K., & Bölte, S.
- Affiliations
- Region Stockholm (SE)
- Karolinska Institutet (SE)
- Karolinska University Hospital (SE)
- University of London (GB)
- Corresponding author
- Bölte, S
- Venue
- Translational Psychiatry
- Published
- 2017-01-31
- Volume
- 7
- Issue
- 1
- Pages
- e1014-e1014
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC5299390
- OpenAlex
- W2583660246
- Cited by
- 35
- References
- 45
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 2 · 2023: 4 · 2022: 3 · 2021: 2 · 2020: 7 · 2019: 4 · 2018: 5 · 2017: 3
- FWCI
- 2.98
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Translational Psychiatry (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- BIROn (Birkbeck, University of London) (acceptedVersion)
- eSpace (Curtin University) (submittedVersion, cc-by)
- Funders
- Kempe Foundation
- Stiftelsen för Strategisk Forskning
- Svenska Forskningsrådet Formas
- Hjärnfonden
- Knut och Alice Wallenbergs Stiftelse
- Vetenskapsrådet
- Forskningsrådet om Hälsa, Arbetsliv och Välfärd
- Stiftelsen Solstickan
- Science for Life Laboratory
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Health Sciences › Medicine › Psychiatry and Mental health › Child Nutrition and Feeding Issues
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- autism spectrum disorder, discordant twins, monozygotic twins, dizygotic twins, environmental risk factors, cumulative environmental exposure, autistic traits, excessive crying, autism screening, early detection
- MeSH terms
- Autism Spectrum Disorder, Adolescent, Adult, Apgar Score, Asthma, Attention Deficit Disorder with Hyperactivity, Autistic Disorder, Birth Weight, Breech Presentation, Cerebral Hemorrhage, Child, Eczema, Environment, Epilepsy, Female, Fetal Distress, Gastroenteritis, Heart Defects, Congenital, Humans, Hydrocephalus, Hypersensitivity, Hypoglycemia, Male, Microcephaly, Otitis Media, Oxygen Inhalation Therapy, Pregnancy, Pyelonephritis, Sleep Wake Disorders, Sweden, Thrombocytopenia, Twins, Dizygotic, Twins, Monozygotic, Vision Disorders, Sepsis, Feeding and Eating Disorders of Childhood, Hyperbilirubinemia, Neonatal, Young Adult
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