Genetic and Environmental Influences on Lobar Brain Structures in Twins With Autism

Abstract

This investigation examined whether the variation of cerebral structure is associated with genetic or environmental factors in children with autism spectrum disorder (ASD) compared with typically developing (TD) controls. T1-weighted magnetic resonance imaging scans were obtained from twin pairs (aged 6-15 years) in which at least one twin was diagnosed with ASD or both were TD. Good quality data were available from 30 ASD, 18 discordant, and 34 TD pairs (n = 164). Structural measures (volume, cortical thickness, and surface area) were generated with FreeSurfer, and ACE modeling was completed. Lobar structures were primarily genetically mediated in TD twins (a2 = 0.60-0.89), except thickness of the temporal (a2 = 0.33 [0.04, 0.63]) and occipital lobes (c2 = 0.61 [0.45, 0.77]). Lobar structures were also predominantly genetically mediated in twins with ASD (a2 = 0.70-1.00); however, thickness of the frontal (c2 = 0.81 [0.71, 0.92]), temporal (c2 = 0.77 [0.60, 0.93]), and parietal lobes (c2 = 0.87 [0.77, 0.97]), and frontal gray matter (GM) volume (c2 = 0.79 [0.63, 0.95]), were associated with environmental factors. Conversely, occipital thickness (a2 = 0.93 [0.75, 1.11]) did not exhibit the environmental contributions that were found in controls. Differences in GM volume were associated with social communication impairments for the frontal (r = 0.52 [0.18, 0.75]), temporal (r = 0.61 [0.30, 0.80]), and parietal lobes (r = 0.53 [0.19, 0.76]). To our knowledge, this is the first investigation to suggest that environmental factors influence GM to a larger extent in children with ASD, especially in the frontal lobe.

Keywords: FreeSurfer; cortical thickness; frontal lobe; heritability; social communication.

Figure 1

ICCs in ACE model space. ICCs from twin pairs in which both twins were diagnosed with ASD or were TD controls, adjusted for gender, were generated separately for MZ and DZ twin pairs and are displayed in relation to ACE model space [a = additive genetics; c = shared family environment; e = unique environment; d = genetic dominance] for the (A) frontal, (B) temporal, (C) parietal, and (D) occipital lobes. Under a primarily environmental CE model, ICCs in MZ and DZ twin pairs are equal or nearly equal, while under primarily genetic AE or DE models, the ICC in MZ twins is approximately twice, or more, that in DZ twin pairs.

Figure 2

Relationships between intra-twin pair differences in GM volume and SCI. Within twin pair differences in lobar GM volume (mm³) and SCIs, as assessed with the SRS, are displayed for DZ and MZ twin pairs in which at least one twin was diagnosed with ASD (squares) or both were TD controls (circles). Pearson’s correlations that survived false discovery rate (Benjamini and Hochberg 1995) correction for multiple comparisons across all lobar structures (solid line) are displayed for ASD twin pairs. There were no significant correlations in TD twins or MZ twins with ASD.