Treatment and Etiology of Depression in Youth Laboratory

Director: Christian A. Webb, PhD.
Lab Website:

The Treatment and Etiology of Depression in Youth (TEDY) Laboratory uses a multimodal approach (EEG, fMRI, ecological momentary assessment, passive smartphone sensor data, laboratory-based experiments, and behavioral paradigms) to investigate the etiology and pathophysiology of depression in adolescents, as well as the mechanisms of change in psychotherapeutic and pharmacological treatments for depression.

Predicting Treatment Outcome in Depression

Greater knowledge of variables predicting better or worse treatment response prior to the start of treatment may have important clinical implications regarding which interventions are best suited for whom, thus informing treatment selection. To date, we have strikingly little empirical data to usefully guide the selection of treatments for depressed individuals. In current clinical practice, treatment selection for depressed individuals is largely based on trial-and-error and clinician/patient preference. Rates of non-response to first line depression treatment in primary care are high (~ 70%), resulting in protracted depressive episodes until an adequate treatment is found. Consistent with the goals of precision medicine, the more recent work of the TEDY Lab is aimed at developing actionable, algorithm-guided treatment recommendations to improve outcomes for depressed individuals by matching them to the optimal intervention. We are currently conducting this research within the context of randomized clinical trials and within real-world psychiatric clinics (e.g., units at McLean Hospital).

Selected publications:

Webb, C. A., Cohen, Z.D., Beard, C., Forgeard, M., Peckham, A., & Björgvinsson, T. (2020). Personalized prognostic prediction of treatment outcome for depressed patients in a naturalistic psychiatric setting: A comparison of machine learning approaches. Journal of Consulting & Clinical Psychology, 88, 25-38.

Webb, C. A., Swords, C., & *Murray, L., & Hilt, L. (in press). App-based mindfulness training for adolescent rumination: Predicting immediate vs. cumulative benefit. Mindfulness.

Webb, C. A., Forgeard, M, *Israel, E., *Lovell-Smith, N.M., Björgvinsson, T & Beard, C. (in press). Personalized prescriptions of therapeutic skills from patient characteristics: An ecological momentary assessment approach. Journal of Consulting & Clinical Psychology

Webb, C. A., Auerbach, R. P., Bondy, E., Stanton, C. H., Appleman, L., & Pizzagalli, D. A. (2021). Reward-related neural predictors and mechanisms of change in cognitive behavioral therapy for depressed adolescent girls. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 6(1), 39-49. [For associated Editorial, see Fryer, 2021;].

Webb, C. A., Trivedi, M.D., Cohen, Z. D, Dillon, D. G., Fournier, J.C., Goer, F., Fava, M. McGrath, P. J., WeissmanM., Parsey, R., Adams, P., Trombello, J. M., Cooper, C., Deldin, P., Oquendo, M. A., McInnis, M.G., Huys, Q., Bruder, G., Kurian, B.T., Jha, M., DeRubeis, R. J., and Pizzagalli D. A. (2019). Personalized prediction of antidepressant versus placebo response: Evidence from the EMBARC study. Psychological Medicine, 49, 1118-1127.

Pizzagalli, D.A.*, Webb, C.A.*, Dillon, D.G., Tenke, C.E., Kayser, J., Goer, F., Fava, M., McGrath, P., Weissman, M., Parsey, R., Adams, P., Trombello, J. M., Cooper, C., Deldin, P., Oquendo, M.A., McInnis, M.G., Carmody, T., Bruder, G., Trivedi, M.H. (2018). Pretreatment rostral anterior cingulate cortex theta activity in relation to symptom improvement in depression: A randomized clinical trial. JAMA Psychiatry, 75, 547-554.  [*Joint First Authorship/Contributed equally]

Webb, C. A., Olson E.A., Killgore W.D.S., Pizzagalli, D. A., Rauch S.L. & Rosso I.M. (2018). Rostral anterior cingulate cortex morphology predicts treatment response to internet-based CBT for depression. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 3, 255-262. [For associated commentary, see Fu, Biological Psychiatry: CNNI, 2018;]

Clarifying the Mechanisms of Change in Psychotherapy for Depression

There is a large body of treatment outcome research attesting to the efficacy of psychotherapies (in particular, cognitive behavioral therapy [CBT]) for depression. However, the mechanisms through which patients improve – and why many fail to sufficiently improve – remain largely unknown, in particular with regards to the treatment of depression in youth. A clearer understanding of the “active ingredients” of treatment and underlying mechanisms of symptom change may ultimately inform the development of more targeted – and ideally more effective and efficient – treatments for depression. My colleagues and I are conducting this research within the context of clinical trials of CBT, mindfulness-based interventions, and Behavioral Activation (BA) therapy. We are examining the role of therapist adherence to, and competence in, CBT techniques in predicting depressive symptom change. In addition, we examine the role of the therapist-patient relationship, as well as patient acquisition and use of various cognitive and behavioral skills.

Selected publications:

Webb, C. A., Singleton, P., Bondy, E., Stanton, C. H., & Pizzagalli, D. A., & Auerbach, R. P. (2019). Cognitive vs. behavioral skills in CBT for depressed adolescents: Disaggregating within-patient vs. between-patient effects on symptom change. Journal of Consulting and Clinical Psychology, 87, 484-490

Webb, C. A., DeRubeis, R. J., & Barber, J. P. (2010). Therapist adherence/competence and treatment outcome: A meta-analytic review. Journal of Consulting and Clinical Psychology, 78, 200-211.

Webb, C. A., Beard, C., Kertz, S. J., Hsu, K. & Björgvinsson, T. (2016). Differential role of CBT skills, DBT skills and psychological flexibility in predicting depressive versus anxiety symptom improvement. Behaviour Research and Therapy, 81, 12-20.

Webb, C. A., DeRubeis, R. J., Dimidjian, S., Hollon, S. D., Amsterdam, J. D. & Shelton, R. C. (2012). Predictors of patient cognitive therapy skills and symptom change in two randomized clinical trials: The role of therapist adherence and the therapeutic alliance. Journal of Consulting and Clinical Psychology, 80, 373-381.

Webb, C. A., DeRubeis, R. J., Amsterdam, J. D., Shelton, R. C., Hollon, S. D., & Dimidjian, S. (2011). Two aspects of the therapeutic alliance: Differential relations with depressive symptom change.Journal of Consulting and Clinical Psychology, 79, 279-283.

Webb, C. A., Beard, C, Auerbach, R P., Menninger, E. & Björgvinsson, T. (2014). The therapeutic alliance in a naturalistic psychiatric setting: Temporal relations with depressive symptom change. Behaviour Research and Therapy, 61, 70-77.

Investigating the Etiology of Depression

Depression rates are low in childhood but surge in adolescence. A clearer understanding of factors that cause and maintain depressive symptoms in adolescents can ultimately help inform and improve interventions aimed at treating and preventing depression in this age group. The NIMH Research Domain Criteria (RDoC) initiative has highlighted the need for research focusing on fundamental dimensions of behavior that cut across traditional diagnostic categories. Accordingly, and in an effort to parse the heterogeneity and etiological/pathophysiological complexity of MDD, our research in this area has focused on relatively less complex intermediate (endo)phenotypes that map more reliably unto underlying neurobiology. Specifically, we have examined behavioral endophenotypes probing central domains specified in the RDoC matrix, including negative valence (e.g., neuroticism), positive valence (e.g., reward learning), and cognitive (cognitive control) systems. Such research may ultimately inform efforts to empirically derive meaningful depression subtypes, as well as suggest treatment targets.

Selected publications:

Webb, C. A., *Israel, E.S., Belleau, E., *Appleman, L., Forbes, E.E., & Pizzagalli, D.A (2021). Mind-wandering in adolescents predicts worse affect and is linked to aberrant default mode network – salience network connectivity. Journal of the American Academy of Child and Adolescent Psychiatry, 60(3), 377-387 [For associated Editorial, see Thai et al., 2020;]

Webb, C. A., Dillon, D. G., Pechtel, P., Goer, F., Murray, M., Huys, Q. J., Fava, M., McGrath, P., Weissman, M., Parsey R., Kurian, B., Adams, P., Weyandt, S., Trombello, J., Grannemann, B., Cooper, C., Deldin, P., Tenke, C., Trivedi, M., Bruder, G., & Pizzagalli, D. P. (2016). Neural correlates of three promising endophenotypes of depression: Evidence from the EMBARC study. Neuropsychopharmacology, 41, 454-463.

Webb, C. A., Auerbach, R. P., Bondy, E., Stanton, C. H., Foti, D. J., & Pizzagalli, D. A., (2017). Abnormal neural responses to feedback in depressed adolescents. Journal of Abnormal Psychology, 126, 19-31.

Webb, C. A., Weber, M., Mundy, E., & Killgore, W. D. S. (2014). Reduced gray matter volume in the anterior cingulate, orbitofrontal cortex and thalamus as a function of mild depressive symptoms: A voxel-based morphometric analysis. Psychological Medicine, 44, 2833-2843.