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Background  The longitudinal course of multiple symptom domains in adolescents treated for major depression is not known. Revealing the temporal course of general and specific psychopathology factors, including potential differences between psychotherapies, may aid therapeutic decision‐making.    Methods  Participants were adolescents with major depressive disorder (aged 11–17; 75% female;  N  = 465) who were part of the IMPACT trial, a randomized controlled trial comparing cognitive behavioral therapy, short‐term psychoanalytic psychotherapy, and brief psychosocial intervention. Self‐reported symptoms at baseline and 6, 12, 36, 52, and 86 weeks postrandomization were analyzed with bifactor modeling.    Results  General psychopathology factor scores decreased across treatment and one‐year follow‐up. Specific melancholic features and depressive cognitions factors decreased from baseline to 6 weeks. Conduct problems decreased across treatment and follow‐up. Anxiety increased by 6 weeks and then reverted to baseline levels. Obsessions–compulsions did not change. Changes in general and specific factors were not significantly different between the three psychotherapies during treatment. During follow‐up, however, conduct problems decreased more in brief psychosocial intervention versus cognitive behavioral therapy (1.02, 95% Bayes credible interval 0.25, 1.96), but not versus short‐term psychoanalytic psychotherapy.    Conclusions  The clinical response signature in this trial is best revealed by rapid reductions in depression symptoms and general psychopathology. Protracted improvements in general psychopathology and conduct problems subsequently occur. Psychosocial treatments for adolescent depression have comparable effects on general and specific psychopathology, although a psychoeducational, goal‐focused approach may be indicated for youth with comorbid conduct problems.

Toward precision therapeutics: general and specific factors differentiate symptom change in depressed adolescents