Several studies using both whole brain and region of interest approaches have explored the effects of familial risk on various brain structures in offspring from high and low-risk families. Deviation of regional brain volume, whether decreases or increases, can be expected to alter brain functioning. The formation of appropriate synaptic connections in the developing brain occurs through a series of progressive events including cell migration, neuronal growth and synaptogenesis but also through regressive events that may lead to reduced volume; all of which are essential for normal brain function (Riccomagno and Kolodkin, 2015). Removal of excessive neuronal connections through axonal pruning appears to be as important as events associated with neuronal growth because disruption of pruning has been linked to some psychiatric disorders (Tang et al., 2014; Glausier and Lewis, 2013). Reduced pruning has been suggested as an explanation for greater total cerebellar volume as well as regional differences that are seen in adolescent and young adult offspring from high-risk (HR) families with multiple cases of AD when contrasted with low-risk (LR) controls (Hill et al., 2011; 2015).
