Discussion
anhedonia, ARI, treatment-refractory, MDD, depression, depressive recall
EVENTS, MALTREATMENT, REMISSION
In a large multicentre trial that included rigorous contextual assessment of childhood maltreatment history, we found that greater severity of mother-perpetrated emotional maltreatment directly predicted lower odds of remission following 16 weeks of treatment with ESC or ESC + ARI. Further, emotional maltreatment perpetrated by the father and physical maltreatment were indirectly associated with remission status through greater severity of (less change in) anhedonia from baseline to week 8. The current design provided a particularly conservative test of our research question. The effect of emotional maltreatment was robust when controlling for overlapping variance with physical and sexual maltreatment, and ROC analysis indicated that a model containing only physical and sexual maltreatment did not predict remission better than chance. Further, the effect of emotional maltreatment on remission at week 16 was robust even over and above the very strong association of response at week 8. Previous cross-sectional research has found that emotional maltreatment is also significantly more strongly associated than other forms of maltreatment with the onset and severity of MDD.Higher severity of emotional and physical maltreatment was associated with greater severity of (less change in) anhedonia following 8 weeks of ESC treatment. Further, the relations of emotional maltreatment perpetrated by the father and physical maltreatment to remission status were significantly Symptoms of anhedonia are more strongly related to threat neurocircuitry than are symptoms of general distress in depression.Maltreatment predicted remission over and above treatment arm (ESC vs. ESC + ARI). Therefore, childhood maltreatment may represent a marker of a more treatment-refractory set of patients who warrant multilevel investigation. In particular, future research is needed to examine other treatment strategies (e.g., new pharmacotherapy augmentation strategiesLimitations include the retrospective nature of the CECA, which raises concerns about depressive recall bias. However, contextual interview measures of childhood maltreatment are less subject to recall bias than traditional self-report measures because ratings are independent and standardized to anchored exemplars.Further, the MADRS includes 1 item related to anhedonia (item 8 “Inability to feel”), raising the potential that our mediator may be confounded with our outcome. However, our measure of anhedonia assesses the much broader domain, capturing interest, motivation, effort, and enjoyment of rewards across several areas of life. Nevertheless, conclusions would be strengthened through future research including behavioural tasks or neurophysiological markers of anhedonia. Finally, it was beyond our scope to examine the developmental timing of maltreatment, proximal stressful life events, or additional psychobiological factors that could potentially mediate or moderate the relation between childhood maltreatment and treatment response.Childhood maltreatment is widely regarded as one of the strongest risk factors for the onset and treatment resistance of MDD. The current results identify which specific early exposures place patients at the greatest risk, thereby allowing these patients to be assigned for more rigorous intervention. Further, they have the potential to inform the development of novel treatments targeting the domains driving nonremission, specifically anhedonia, with the ultimate goal of reducing the burden associated with MDD.