Numerous genetic studies have demonstrated that schizophrenia, bipolar disorder and ADHD are highly heritable disorders. For schizophrenia, illness risk exceeds 40% in monocygotic twins and 6.5% in first degree relatives (Cardno et al. 1999; Kendler et al. 1993). Similar heritability estimates have been found for bipolar disorder (Kieseppä et al. 2004) and ADHD has been reported to have even higher heritability between 60% and 90% (Todd 2000; Faraone et al. 2005).


Despite this, studies investigating genetic markers of these illnesses at a whole-genome level have had limited success in explaining substantial parts of this heritable variance, likely in part because the genetic architecture is complex and includes pleiotropic, epistatic as well as gene-environment interaction contributions. At the individual marker level, observed genetic variation is partially consistent with changes in neurotransmitter (e.g. dopamine) systems hypothesized to be involved in the diseases’ aetiologies. Additionally, genetic association studies have implicated other biological processes in the aetiology of mental illnesses, such as neurodevelopment, neuron differentiation and cell structural processes, including synaptic scaffolding (Addington and Rapoport 2011). At the brain level, a broad spectrum of illness associated differences including structural and functional changes have been observed using imaging technologies.


Most of these studies have, however, been performed in small cohorts and have not been validated in independent datasets. In particular for schizophrenia, numerous studies have also investigated changes in peripheral molecular systems and found abnormalities in glucose metabolism, immunological changes and altered growth factor levels (Insel 2010).


Nevertheless, this evidence has so far been correlative without a clear link to potential aetiological processes affecting brain function. This is likely due to lack of multi-modal investigations where genetic, imaging and other data are combined in a single analytic framework.