Genetic and environmental influences on structural brain measures in twins with autism spectrum disorder

Abstract

Atypical growth patterns of the brain have been previously reported in autism spectrum disorder (ASD) but these alterations are heterogeneous across individuals, which may be associated with the variable effects of genetic and environmental influences on brain development. Monozygotic (MZ) and dizygotic (DZ) twin pairs with and without ASD (aged 6-15 years) were recruited to participate in this study. T1-weighted MRIs (n = 164) were processed with FreeSurfer to evaluate structural brain measures. Intra-class correlations were examined within twin pairs and compared across diagnostic groups. ACE modeling was also completed. Structural brain measures, including cerebral and cerebellar gray matter (GM) and white matter (WM) volume, surface area, and cortical thickness, were primarily influenced by genetic factors in TD twins; however, mean curvature appeared to be primarily influenced by environmental factors. Similarly, genetic factors accounted for the majority of variation in brain size in twins with ASD, potentially to a larger extent regarding curvature and subcortical GM; however, there were also more environmental contributions in twins with ASD on some structural brain measures, such that cortical thickness and cerebellar WM volume were primarily influenced by environmental factors. These findings indicate potential neurobiological outcomes of the genetic and environmental risk factors that have been previously associated with ASD and, although preliminary, may help account for some of the previously outlined neurobiological heterogeneity across affected individuals. This is especially relevant regarding the role of genetic and environmental factors in the development of ASD, in which certain brain structures may be more sensitive to specific influences.

Fig. 1

ICCs in ACE model space. Intra-class correlation coefficients (ICC) in a all participants, adjusted for diagnosis and gender, and separately within twin pairs in which both twins were diagnosed with b autism spectrum disorder (ASD) or were c typically-developing (TD) controls, adjusted for gender, were generated within monozygotic (MZ) and dizygotic (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]. Brain structures above or near the CE line are primarily environmentally-mediated whereas brain structures below or near the DE line are primarily genetically-mediated