Introduction
maltreatment, anhedonia, sexual abuse, ARI, depressive disorder, MDD, depression, Depression, disability
REMISSION, SYNDROME
Major depressive disorder (MDD) affects close to 300 million people globally and is the leading worldwide cause of disability.Childhood maltreatment, including a history of emotional, physical, and/or sexual abuse, represents a particularly promising marker. Childhood maltreatment is the strongest developmental risk factor for MDD,The real promise of personalized medicine requires consideration of the prognostic significance of individual differences at the level of the risk marker (maltreatment) and the syndrome. Therefore, part of the reason for discrepancies in findings across studies may be due to the failure to consider the heterogeneous nature of childhood maltreatment and MDD.First, childhood maltreatment is a broad construct that includes distinct exposures that are associated with distinct neurobiological correlatesTo our knowledge, no studies have examined whether treatment efficacy in depression is differentially impacted by emotional versus physical versus sexual maltreatment. Further, no studies to our knowledge have examined change in anhedonia as a differential mediator of ADM outcome in those with histories of emotional versus physical versus sexual maltreatment. These are important questions as identifying which specific childhood histories are the strongest predictors of nonresponse may identify patients to be targeted for more rigorous intervention. Further, results bearing on mechanisms have the potential to inform the development of novel treatments targeting the domains driving nonremission.We examine our research questions in the context of the 16-week, 6-site Canadian Biomarker Integration Network in Depression (CAN-BIND)-1 trial, in which patients with MDD were treated with ESC for 8 weeks; nonresponders were then augmented with aripiprazole (ARI)—a partial D2 receptor agonist that elevates dopaminergic signalling—for an additional 8 weeks.We hypothesized that (1) emotional maltreatment, particularly perpetrated by the mother, will emerge as the strongest negative predictor of remission status at week 16 relative to physical or sexual maltreatment; (2) greater severity of emotional maltreatment, but not physical or sexual maltreatment, will be significantly associated with greater odds of requiring ARI augmentation (i.e., treatment nonresponse at week 8); and (3) severity of anhedonia at week 8 will significantly mediate the relation of emotional maltreatment to week 16 remission status.