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

ABSTRACT: 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.

SUBMITTER: Aitken M

PROVIDER: S-EPMC7496892 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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

Aitken Madison M Haltigan John D JD Szatmari Peter P Dubicka Bernadka B Fonagy Peter P Kelvin Raphael R Midgley Nick N Reynolds Shirley S Wilkinson Paul O PO Goodyer Ian M IM

Journal of child psychology and psychiatry, and allied disciplines 20200112 9

<h4>Background</h4>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.<h4>Methods</h4>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 beh ...[more]

PMID: 31930507

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Project description:BackgroundApproximately half of depressed adolescents fail to respond to cognitive behavioral therapy (CBT). Given the variability in response, it is important to identify pretreatment characteristics that predict prognosis. Knowledge of which depressed adolescents are likely to exhibit a positive versus poor outcome to CBT may have important clinical implications (e.g., informing treatment recommendations). Emerging evidence suggests that neural reward responsiveness represents one promising predictor.MethodsAdolescents with major depressive disorder (n = 36) received CBT and completed a reward task at 3 time points (pretreatment, midtreatment and posttreatment) while 128-channel electroencephalographic data were acquired. Healthy control participants (n = 29) completed the same task at 3 corresponding time points. Analyses focused on event-related potentials linked to 2 stages of neural processing: initial response to rewards (reward positivity) and later, elaborative processing (late positive potential). Moreover, time-frequency analyses decomposed the reward positivity into 2 constituent components: reward-related delta and loss-related theta activity.ResultsMultilevel modeling revealed that greater pretreatment reward responsiveness, as measured by the late positive potential to rewards, predicted greater depressive symptom change. In addition, a group × condition × time interaction emerged for theta activity to losses, reflecting normalization of theta power in the group with major depressive disorder from baseline to posttreatment.ConclusionsAn event-related potential measure of sustained (late positive potential)-but not initial (reward positivity)-reward responsiveness predicted symptom improvement, which may help inform which depressed adolescents are most likely to benefit from CBT. In addition to alleviating depression, successful CBT may attenuate underlying neural (theta) hypersensitivity to negative outcomes in depressed youths.

Project description:Purpose/backgroundHeterogeneity has been documented in trajectories of symptom change during antidepressant treatment for major depressive disorder (MDD). It is unclear whether distinct trajectories of change exist for functioning during antidepressant treatment.Methods/proceduresThis analysis explored distinct trajectories of functioning in MDD and tested whether they corresponded to trajectories of symptom change. Data were from 4317 patients and were pooled from 9 randomized placebo-controlled trials. Growth mixture modeling was used to identify trajectories of Hamilton Rating Scale for Depression (HRSD) and Sheehan Disability Scale (SDS) for placebo- and desvenlafaxine-treated patients.Findings/resultsThree trajectories were identified for symptoms (HRSD) in patients receiving placebo (mean reduction baseline to week 8, -18.4 [most favorable] to -2.6 points [least favorable]). Four HRSD trajectories were identified for patients receiving desvenlafaxine (mean reduction from baseline to week 8, -17.2 [most favorable] to -2.6 points [least favorable]). Four trajectories were identified for functioning (SDS) in patients receiving placebo (mean reduction baseline to week 8, -13.6 [most favorable] to -0.8 points [least favorable]), and 3 for desvenlafaxine (-12.8 to -1.4 points, respectively). Percentages of agreement between most favorable HRSD and SDS trajectories were 75% (placebo) and 85% (desvenlafaxine), and for least favorable trajectories were 88% (placebo) and 80% (desvenlafaxine).Implications/conclusionsDistinct trajectories of change based on symptoms and functioning were identified among patients with MDD receiving desvenlafaxine and among patients with MDD receiving placebo. Differentiating subpopulations of patients has the potential to provide a more personalized treatment of patients with MDD.ClinicalTrials.govIdentifiers: NCT00072774; NCT00277823; NCT00300378; NCT00384033; NCT00798707; NCT00863798; NCT01121484; NCT00824291; NCT01432457.

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

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

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