Figure 1. Imaging Genetics and Genomics Models.

(A) The traditional imaging genetics and genomics model suggests that genetic variation confers risk for psychopathology indirectly through its influence on the brain. This theoretical model is well suited for traditional mediation models estimating indirect associations (demarcated with the dashed line), through which genetic background is linked to behavior through neural phenotypes. (B) Imaging genetics and imaging genomics redux: In the future, as imaging genetics and genomics expand to include larger and longitudinal samples it will be possible to evaluate a more complete interactive model in which bidirectional relationships between the genome, brain, and behavior may be investigated in the context of environmental experience and peripheral biological markers. For example, socioeconomic status has been associated with epigenetic modifications that are, in turn, related to psychiatrically-relevant brain function (145). Moreover, environmental experience (e.g., trauma experienced during early life) moderates genetic associations with neural phenotypes and associations between neural phenotypes and behavior (20,146). Further, genetic background influences peripheral indices such as gut microbiome (147), which in turn has been linked to neural phenotypes and psychopathology (148). As a result, a more complete mechanistic understanding requires multiple levels of analyses in the context of longitudinal and convergent data. Currently, convergence across multiple methods and studies testing legs separately is attainable. Informed by such studies, in the future, as large multimodal longitudinal studies develop, it is plausible that more complete pathways could be tested in the framework of a single study.