Preclinical neuroimaging of gene-environment interactions in psychiatric disease

Psychiatric disease is one of the leading causes of disability worldwide. Despite the global burden and need for accurate diagnosis and treatment of mental illness, psychiatric diagnosis remains largely based on patient-reported symptoms, allowing for immense symptomatic heterogeneity within a single disease. In renewed efforts towards improved diagnostic specificity and subsequent evaluation of treatment response, a greater understanding of the underlying of the neuropathology and neurobiology of neuropsychiatric disease is needed. However, dissecting these mechanisms of neuropsychiatric illness in clinical populations are problematic with numerous experimental hurdles limiting hypothesis-driven studies including genetic confounds, variable life experiences, different environmental exposures, therapeutic histories, as well as the inability to investigate deeper molecular changes in vivo . Preclinical models, where many of these confounding factors can be controlled, can serve as a crucial experimental bridge for studying the neurobiological origins of mental illness. Furthermore, although behavioral studies and molecular studies are relatively common in these model systems, focused neuroimaging studies are very rare and represent an opportunity to link the molecular changes in psychiatric illness with advanced quantitative neuroimaging studies. In this review, we present an overview of well-validated genetic and environmental models of psychiatric illness, discuss gene-environment interactions, and examine the potential role of neuroimaging towards understanding genetic, environmental, and gene-environmental contributions to psychiatric illness.