Genetic and environmental influences on corticostriatal circuits in twins with autism

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Hegarty, J. P., Lazzeroni, L. C., Raman, M. M., Hallmayer, J. F., Cleveland, S. C., Wolke, O. N., Phillips, J. M., Reiss, A. L., & Hardan, A. Y. (2020). Genetic and environmental influences on corticostriatal circuits in twins with autism. Journal of Psychiatry and Neuroscience, 45(3), 188-197. https://doi.org/10.1503/jpn.190030

Publication date: 28 Apr 2020 Added to AutiHub: 5 Oct 2026 Type: Article Article language: English
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Authors

Publication authors
9
Publication authors identified as autistic
1 / 9 (11.1%)
  1. John P. Hegarty *
  2. Laura C. Lazzeroni
  3. Mira M. Raman
  4. Joachim F. Hallmayer
  5. Sue C. Cleveland
  1. Olga N. Wolke
  2. Jennifer M. Phillips
  3. Allan L. Reiss
  4. Antonio Y. Hardan

Abstract

Background: Corticostriatal circuits (CSC) have been implicated in the presentation of some restricted and repetitive behaviours (RRBs) in children with autism-spectrum disorder (ASD), and preliminary evidence suggests that disruptions in these pathways may be associated with differences in genetic and environmental influences on brain development. The objective of this investigation was to examine the impact of genetic and environmental factors on CSC regions in twins with and without ASD and to evaluate their relationship with the severity of RRBs. Methods: We obtained T 1 -weighted MRIs from same-sex monozygotic and dizygotic twin pairs, aged 6–15 years. Good-quality data were available from 48 ASD pairs (n = 96 twins; 30 pairs concordant for ASD, 15 monozygotic and 15 dizygotic; 18 pairs discordant for ASD, 4 monozygotic and 14 dizygotic) and 34 typically developing control pairs (n = 68 twins; 20 monozygotic and 14 dizygotic pairs). We generated structural measures of the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), caudate, putamen, pallidum and thalamus using FreeSurfer. Twin pair comparisons included intraclass correlation analyses and ACE modelling (a 2 = additive genetics; c 2 = common or shared environment; e 2 = unique or nonshared environment). We also assessed correlations with RRB severity. Results: Structural variation in CSC regions was predominantly genetically mediated in typically developing twins (a 2 = 0.56 to 0.87), except for ACC white matter volume (a 2 = 0.42, 95% confidence interval [CI] 0.08 to 0.77). We also observed similar magnitudes of genetic influence in twins with ASD (a 2 = 0.65 to 0.97), but the cortical thickness of the ACC (c 2 = 0.44, 95% CI 0.22 to 0.66) and OFC (c 2 = 0.60, 95% CI 0.25 to 0.95) was primarily associated with environmental factors in only twins with ASD. Twin pair differences in OFC grey matter volume were also correlated with RRB severity and were predominantly environmentally mediated. Limitations: We obtained MRIs on 2 scanners, and analytical approaches could not identify specific genetic and environmental factors. Conclusion: Genetic factors primarily contribute to structural variation in subcortical CSC regions, regardless of ASD, but environmental factors may exert a greater influence on the development of grey matter thickness in the OFC and ACC in children with ASD. The increased vulnerability of OFC grey matter to environmental influences may also mediate some heterogeneity in RRB severity in children with ASD.

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Cited references
65
With a DOI
56
Without a DOI, from raw bibliography text
8
2 / 65 (3.1%) cited references include at least one author identified as autistic.
References with data to complete
5 / 65 (7.7%)
References with detected author names
62 / 65 (95.4%)
Without detected author names
3
Without a structured title
3
Without a stable identifier
7
References with raw author names still to review
0
References with external metadata lookup issues
3
These indicators apply to cited references displayed on this page, after technical duplicates have been merged. A reference without a DOI can still support author statistics when a title and author names are available.
Author names detected in the cited bibliography
378
From DOI or external metadata
378
From validated raw bibliography text
0
Raw names already validated
0
Raw names still to review
0
89 / 378 (23.5%) names are linked to an author already present in AutiHub. 289 / 378 (76.5%) names are not yet linked.
Names linked to a person identified as autistic
2 / 378 (0.5%)
Calculated across all author names detected in the cited bibliography. Among names linked to an author already present in AutiHub: 2 / 89 (2.2%). Distinct people identified as autistic: 1 / 290 (0.3%).
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