Psychiatric neuroimaging at a crossroads: Insights from psychiatric genetics

Thanks to methodological advances, large-scale data collections, and longitudinal designs, psychiatric neuroimaging is better equipped than ever to identify the neurobiological underpinnings of youth mental health problems. However, the complexity of such endeavors has become increasingly evident, as the field has been confronted by limited clinical relevance, inconsistent results, and small effect sizes. Some of these challenges parallel those historically encountered by psychiatric genetics. In past genetic research, robust findings were historically undermined by oversimplified biological hypotheses, mistaken assumptions about expectable effect sizes, replication problems, confounding by population structure, and shared biological patterns across disorders. Overcoming these challenges has contributed to current successes in the field. Drawing parallels across psychiatric genetics and neuroimaging, we identify key shared challenges as well as pinpoint relevant insights that could be gained in psychiatric neuroimaging from the transition that occurred from the candidate gene to (post) genome-wide “eras” of psychiatric genetics. Finally, we discuss the prominent developmental component of psychiatric neuroimaging and how that might be informed by epidemiological and omics approaches. The evolution of psychiatric genetic research offers valuable insights that may expedite the resolution of key challenges in psychiatric neuroimaging, thus potentially moving our understanding of psychiatric pathophysiology forward.