The relationship between family history of depression and brain structure and function: a systematic review of large cohorts.
Review
Overview
abstract
Family history (FH) of major depression is a well-replicated risk factor for developing the disorder. Studying individuals who may be at high familial risk but are symptom free may allow us to better distinguish mechanisms predisposing individuals to depression from those that arise from having the disorder. Neuroimaging studies, employing such high-risk designs, have suggested several cortical and subcortical regions that may contribute to depression susceptibility; however, specificity, timing of mechanisms, and long-term clinical implications remain unclear. As developing de novo cohorts to address these questions would be resource demanding, we sought to identify existing, longitudinal cohorts that could be used to examine the effects of family history on brain imaging outcomes rigorously and cost-effectively; to determine how family history was assessed in these cohorts; and to summarize their major findings published to date. A structured PUBMED search identified 25 longitudinal cohorts (13 countries), each containing ≥1,000 participants, direct- or informant-based family history, psychiatric measures, and ≥1 MRI collection. Across publications from these cohorts, subcortical (particularly striatum, amygdala) and cortical (anterior cingulate, prefrontal) regions most frequently showed alterations in association with familial risk. However, current evidence for whether these regions predicted psychopathology was limited and should be examined in future studies as offspring in these cohorts age. This comprehensive review should also serve as a resource for further analyses of existing data from cohorts with family history and neuroimaging data in the context of depression and other disorders.
