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Chapter 6
Heritability of childhood resting state connectivity
The second aim of this study was to examine the heritability of childhood resting state connections, specifically focusing on connections between the ventral striatum and amygdala with prefrontal cortex and other subcortical regions. Variance in the majority of connections from the ventral striatum to the prefrontal cortex was best described by genetics, with moderately strong heritability factors (up to 67%). Weaker ventral striatum-prefrontal cortex connections have been linked to psychiatric disorders such as depression (Russo and Nestler, 2013) and substance abuse (Deadwyler et al., 2004), which are thought to have a genetic component (Bouchard and McGue, 2003; Flint and Kendler, 2014). The association between genotypic characteristics and psychiatric disorders might be mediated by genetically based connectivity in the brain (Hyman, 2000). Interestingly, connectivity from the ventral striatum to the vACC and thalamus was mostly influenced by shared and unique environmental factors, which is in line with previous findings that reported environmental plasticity of the striatum (Tottenham and Galvan, 2016). These results suggest that long-range cortical-striatal connectivity is more strongly influenced by genetic profiles, while short range thalamic and vACC connectivity is more influenced by environmental factors.
With the exception of ventral striatum-thalamic connectivity, limbic/subcortical-subcortical connectivity was notably influenced by genetics, with heritability estimates ranging from 32-42%. For instance, we found heritability for amygdala-hippocampus connectivity (A=32%), indicating that this emotional memory network (Phelps, 2004) is influenced by genetic factors. Interestingly, a broad literature has shown that these two regions independently are affected by environmental influences such as stress and early adversity (Lupien et al., 2009; Tottenham and Sheridan, 2009; Barch et al., 2016). This raises new questions with respect to how the amygdala-hippocampus circuitry is shaped and develops during child development. Moreover, while ventral striatum-prefrontal cortex connective showed large genetic influences, amygdala-prefrontal cortex connectivity showed mostly effects of the environment, with high estimates of the E component (up to 92%). There were two exceptions to this general pattern. First, in line with the ventral striatum, amygdala-vACC connectivity showed influences of the shared environment. The vACC has been shown to signal for socially salient cues such as peer feedback, both in adults as well as in children (Somerville et al., 2006; Achterberg et al., 2016b; Achterberg et al., 2018b). Connectivity between the vACC and limbic/subcortical regions might also be susceptible to social context and social environmental factors, as these connections are significantly influenced by environment (Gee et al., 2014). Secondly, 54% of the variance in amygdala-OFC connectivity was explained by genetic influences. Interestingly, Whittle and colleagues (2014) have reported longitudinal effects of positive parenting on structural development of the amygdala and OFC. Our study is the first to show
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