Subjects
For the volumetric measures at baseline, 198 MZ and 283 DZ twin pairs had acceptable quality data and were included in the analysis. For diffusion analysis, 145 MZ and 211 DZ twin pairs were included at baseline. At two-year follow-up the corresponding numbers were 146/186 and 127/148 for volume and diffusion respectively. While two of the three sites recruited roughly equal numbers of MZ/DZ twins (83/101 and 86/90), the third site recruited a higher proportion of DZ twins (56/120). The MZ and DZ groups did not differ significantly in age, sex, household income, parental education, or race/ethnicity (Table 1).
Baseline Results
Intraclass correlations (ICCs) for MZ and DZ twin pairs for each region and metric at baseline are shown in Fig. 1. For MZ twins, ICCs ranged from 0.624 (caudate) to 0.861 (pallidum) for RNI, 0.386 (ventral diencephalon) to 0.673 (putamen) for MD, and 0.638 (pallidum) to 0.881 (brain stem) for volumes. For all regions and metrics, the ICCs for DZ twins were significantly less than those from MZ twins, indicating genetic contributions.
Structural equation modelling estimates of the additive genetic, common, and unique environmental contributions to each region and metric are shown in Fig. 2 (top). Heritability estimates for RNI at baseline in the pallidum (0.862, 0.820–0.893), putamen (0.845, 0.798–0.879), and thalamus (0.849, 0.803–0.883) were especially high. For MD, heritability was generally lower than for RNI, but highest in the putamen (0.686, 0.596–0.756) and thalamus (0.676, 0.580–0.751). For structure volumes, the brainstem (0.880 0.850–0.903), caudate (0.881, 0.851–0.904), and putamen (0.870, 0.835–0.896) were found to be highly heritable.
Only the RNI signal in the amygdala showed weakly trending evidence of an influence of the common environment (C = 0.218, -0.007-0.416).
Two-Year Follow-Up Results
The contributions to each region and metric are shown in Fig. 2 (bottom). Heritability estimates for RNI showed a similar pattern at two-year follow-up, with the pallidum (0.819, 0.758–0.863), putamen (0.838, 0.612-1.000) and thalamus (0.830, 0.775–0.870) again demonstrating the highest heritability. For MD, the amygdala, caudate, hippocampus, pallidum, putamen, and thalamus had similar heritabilities, with estimates in the range of 0.571 to 0.688. As at baseline, structure volumes were most highly heritable for the brainstem (0.878, 0.841–0.906), caudate (0.909, 0.881–0.930), and putamen (0.881, 0.845–0.908).
The contribution of the common environment to MD in the nucleus accumbens (0.358, 0.056–0.640) was individually significant, albeit not after correction for multiple comparisons. With the exception of MD in the nucleus accumbens, there were no significant differences in the heritability estimates between baseline and two-year follow-up.
Stability of Measures and Heritability Estimates
The Pearson correlations between measures at baseline and two-year follow-up for the wider ABCD sample are shown in Fig. 3. For RNI, the correlations ranged from 0.717 (amygdala) to 0.879 (pallidum). For MD, the correlations were substantially lower, ranging from 0.388 (ventral diencephalon) to 0.751 (pallidum). The volume of the pallidum displayed the lowest correlation between time points (0.647), while the caudate was highest (0.931).
Figure 4 shows that those measures that were stable between time points (r = 0.87–0.93, pallidum, putamen, thalamus for RNI, and brainstem, caudate and putamen for volume) demonstrated the highest heritability estimates (0.84–0.88 at baseline; 0.82–0.91 at two-year follow-up). Conversely, those measures that were least stable showed relatively low heritabilities (such as MD in the brain stem, nucleus accumbens, and ventral diencephalon).