Abstract
Anhedonia is a cardinal characteristic of depression which predicts worse treatment outcome and is among the most common residual symptoms following treatment. Behavioral Activation (BA) has been shown to be an effective treatment for depressed adults, and more recently, depressed adolescents. Given its emphasis on systematically and gradually increasing exposure to and engagement with rewarding activities and experiences, BA may be a particularly effective intervention for adolescents experiencing anhedonia and associated reward system dysfunction. In the present study, anhedonic adolescents (AA; n = 39) received 12 weekly sessions of BA and completed a multimodal (i.e., neural, behavioral, and self-report [ecological momentary assessment]) assessment of reward function at pre-treatment and post-treatment (as well as weekly self-report assessments of anhedonia). Typically developing adolescents (TDA; n = 41) completed the same measures at corresponding timepoints. Multilevel models tested pre-treatment reward-related predictors of anhedonia improvement, as well as change in reward measures over the course of BA. Analyses revealed significant reductions in anhedonia following BA treatment. Enhanced pre-treatment neural (striatal) reward responsiveness predicted greater anhedonia improvement. In contrast, baseline self-report and behavioral reward measures did not predict treatment outcome. A group x time interaction revealed greater increases in both reward- and loss-related neural responsiveness among AA relative to TDA adolescents. Consistent with a capitalization (rather than compensatory) model, pre-treatment neural – but not self-report or behavioral – measures of relatively enhanced reward responsiveness predicted better BA outcome. In addition to alleviating anhedonia, successful BA may also increase neural sensitivity to affectively salient (e.g., reward- and loss-related) stimuli among anhedonic youth.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Avenevoli S, Swendsen J, He J-P, Burstein M, Merikangas KR. Major depression in the national comorbidity survey–adolescent supplement: prevalence, correlates, and treatment. J Am Acad Child Adolesc Psychiatry. 2015;54:37–44.e2.
Eckshtain D, Kuppens S, Ugueto A, Ng MY, Vaughn-Coaxum R, Corteselli K, et al. Meta-analysis: 13-year follow-up of psychotherapy effects on youth depression. J Am Acad Child Adolesc Psychiatry. 2020;59:45–63.
Weersing VR, Jeffreys M, Do M-CT, Schwartz KT, Bolano C. Evidence base update of psychosocial treatments for child and adolescent depression. J Clin Child Adolesc Psychol. 2017;46:11–43.
Walkup JT. Antidepressant efficacy for depression in children and adolescents: industry- and NIMH-funded studies. Am J Psychiatry. 2017;174:430–7.
Goodyer IM, Reynolds S, Barrett B, Byford S, Dubicka B, Hill J, et al. Cognitive behavioural therapy and short-term psychoanalytical psychotherapy versus a brief psychosocial intervention in adolescents with unipolar major depressive disorder (IMPACT): a multicentre, pragmatic, observer-blind, randomised controlled superiority trial. Lancet Psychiatry. 2017;4:109–19.
Orchard F, Pass L, Marshall T, Reynolds S. Clinical characteristics of adolescents referred for treatment of depressive disorders. Child Adolesc Ment Health. 2017;22:61–68.
Bringmann LF, Lemmens LHJM, Huibers MJH, Borsboom D, Tuerlinckx F. Revealing the dynamic network structure of the Beck Depression Inventory-II. Psychol Med. 2015;45:747–57.
McMakin DL, Olino TM, Porta G, Dietz LJ, Emslie G, Clarke G, et al. Anhedonia predicts poorer recovery among youth with selective serotonin reuptake inhibitor-treatment resistant depression. J Am Acad Child Adolesc Psychiatry. 2012;51:404–11.
Auerbach RP, Millner AJ, Stewart JG, Esposito EC. Identifying differences between depressed adolescent suicide ideators and attempters. J Affect Disord. 2015;186:127–33.
Nierenberg AA. Residual symptoms in depression: prevalence and impact. J Clin Psychiatry. 2015;76:e1480–e1480.
Dunn BD, German RE, Khazanov G, Xu C, Hollon SD, DeRubeis RJ. Changes in positive and negative affect during pharmacological treatment and cognitive therapy for major depressive disorder: a secondary analysis of two randomized controlled trials. Clin Psychol Sci. 2020;8:36–51.
Craske MG, Meuret AE, Ritz T, Treanor M, Dour H, Rosenfield D. Positive affect treatment for depression and anxiety: a randomized clinical trial for a core feature of anhedonia. J Consult Clin Psychol. 2019;87:457–71.
Landén M, Högberg P, Thase ME. Incidence of sexual side effects in refractory depression during treatment with citalopram or paroxetine. J Clin Psychiatry. 2005;66:8892.
McCabe C, Mishor Z, Cowen PJ, Harmer CJ. Diminished neural processing of aversive and rewarding stimuli during selective serotonin reuptake inhibitor treatment. Biol Psychiatry. 2010;67:439–45.
Price J, Cole V, Goodwin GM. Emotional side-effects of selective serotonin reuptake inhibitors: qualitative study. Br J Psychiatry. 2009;195:211–7.
Webb CA, Auerbach RP, Bondy E, Stanton CH, Appleman L, Pizzagalli DA. Reward-related neural predictors and mechanisms of symptom change in cognitive behavioral therapy for depressed adolescent girls. Biol Psychiatry Cogn Neurosci Neuroimaging. 2021;6:39–49.
Dimidjian S, Hollon SD, Dobson KS, Schmaling KB, Kohlenberg RJ, Addis ME, et al. Randomized trial of behavioral activation, cognitive therapy, and antidepressant medication in the acute treatment of adults with major depression. J Consult Clin Psychol. 2006;74:658–70.
Forbes CN. New directions in behavioral activation: using findings from basic science and translational neuroscience to inform the exploration of potential mechanisms of change. Clin Psychol Rev. 2020;79:101860.
Stein AT, Carl E, Cuijpers P, Karyotaki E, Smits JAJ. Looking beyond depression: a meta-analysis of the effect of behavioral activation on depression, anxiety, and activation. Psychol Med. 2021;51:1491–504.
McCauley E, Gudmundsen G, Schloredt K, Martell C, Rhew I, Hubley S, et al. The adolescent behavioral activation program: adapting behavioral activation as a treatment for depression in adolescence. J Clin Child Adolesc Psychol. 2015;0:1–14.
Ritschel LA, Ramirez CL, Cooley JL, Edward, Craighead W. Behavioral activation for major depression in adolescents: results from a pilot study. Clin Psychol Sci Pr. 2016;23:39–57.
Tindall L, Mikocka‐Walus A, McMillan D, Wright B, Hewitt C, Gascoyne S. Is behavioural activation effective in the treatment of depression in young people? A systematic review and meta‐analysis. Psychol Psychother. 2017;90:770–96.
Martell CR, Dimidjian S, Herman-Dunn R. Behavioral activation for depression: a clinician’s guide. New York, NY: Guilford Press; 2013.
McCauley E, Schloredt KA, Gudmundsen GR, Martell CR, Dimidjian S. Behavioral activation with adolescents: a clinician’s guide. New York, NY: Guilford Publications; 2016.
Webb CA, Stanton CH, Bondy E, Singleton P, Pizzagalli DA, Auerbach RP. Cognitive versus behavioral skills in CBT for depressed adolescents: disaggregating within-patient versus between-patient effects on symptom change. J Consult Clin Psychol. 2019;87:484–90.
Leventhal AM, Unger JB, Audrain-McGovern J, Sussman S, Volk HE, Strong DR. Measuring anhedonia in adolescents: a psychometric analysis. J Pers Assess. 2015;97:506–14.
Snaith RP, Hamilton M, Morley S, Humayan A, Hargreaves D, Trigwell P. A scale for the assessment of hedonic tone the Snaith-Hamilton Pleasure Scale. Br J Psychiatry. 1995;167:99–103.
Auerbach RP, Admon R, Pizzagalli DA. Adolescent depression: stress and reward dysfunction. Harv Rev Psychiatry. 2014;22:139–48.
Murray L, Israel ES, Balkind EG, Pastro B, Lovell-Smith N, Lukas SE, et al. Multi-modal assessment of reward functioning in adolescent anhedonia. Psychol Med. 2022:1–10.
Keren H, O’Callaghan G, Vidal-Ribas P, Buzzell GA, Brotman MA, Leibenluft E, et al. Reward processing in depression: a conceptual and meta-analytic review across fMRI and EEG studies. Am J Psychiatry. 2018;175:1111–20.
Rappaport BI, Kandala S, Luby JL, Barch DM. Brain reward system dysfunction in adolescence: current, cumulative, and developmental periods of depression. Am J Psychiatry. 2020;177:754–63.
Borsini A, Wallis ASJ, Zunszain P, Pariante CM, Kempton MJ. Characterizing anhedonia: a systematic review of neuroimaging across the subtypes of reward processing deficits in depression. Cogn Affect Behav Neurosci. 2020;20:816–41.
Pizzagalli DA, Roberts AC. Prefrontal cortex and depression. Neuropsychopharmacology 2022;47:225–46.
Forbes EE, Dahl RE. Research review: altered reward function in adolescent depression: what, when and how? J Child Psychol Psychiatry. 2012;53:3–15.
Morgan JK, Olino TM, McMakin DL, Ryan ND, Forbes EE. Neural response to reward as a predictor of increases in depressive symptoms in adolescence. Neurobiol Dis. 2013;52:66–74.
Stringaris A, Vidal-Ribas Belil P, Artiges E, Lemaitre H, Gollier-Briant F, Wolke S, et al. The Brain’s response to reward anticipation and depression in adolescence: dimensionality, specificity, and longitudinal predictions in a community-based sample. Am J Psychiatry. 2015;172:1215–23.
Hanson JL, Hariri AR, Williamson DE. Blunted ventral striatum development in adolescence reflects emotional neglect and predicts depressive symptoms. Biol Psychiatry. 2015;78:598–605.
Pizzagalli DA, Jahn AL, O’Shea JP. Toward an objective characterization of an anhedonic phenotype: a signal-detection approach. Biol Psychiatry. 2005;57:319–27.
Pizzagalli DA, Iosifescu D, Hallett LA, Ratner KG, Fava M. Reduced hedonic capacity in major depressive disorder: evidence from a probabilistic reward task. J Psychiatr Res. 2008;43:76–87.
Vrieze E, Pizzagalli DA, Demyttenaere K, Hompes T, Sienaert P, de Boer P, et al. Reduced reward learning predicts outcome in major depressive disorder. Biol Psychiatry. 2013;73:639–45.
Belleau EL, Kremens R, Ang Y-S, Pisoni A, Bondy E, Durham K, et al. Reward functioning abnormalities in adolescents at high familial risk for depressive disorders. Biol Psychiatry Cogn Neurosci Neuroimaging. 2021;6:270–9.
Pizzagalli DA. Depression, stress, and anhedonia: toward a synthesis and integrated model. Annu Rev Clin Psychol. 2014;10:393–423.
Santesso DL, Dillon DG, Birk JL, Holmes AJ, Goetz E, Bogdan R, et al. Individual differences in reinforcement learning: behavioral, electrophysiological, and neuroimaging correlates. NeuroImage 2008;42:807–16.
Vrieze E, Ceccarini J, Pizzagalli DA, Bormans G, Vandenbulcke M, Demyttenaere K, et al. Measuring extrastriatal dopamine release during a reward learning task. Hum Brain Mapp. 2013;34:575–86.
Luking KR, Neiman JS, Luby JL, Barch DM. Reduced hedonic capacity/approach motivation relates to blunted responsivity to gain and loss feedback in children. J Clin Child Adolesc Psychol J Soc Clin Child Adolesc Psychol Am Psychol Assoc Div. 2017;46:450–62. 53
Luking KR, Pagliaccio D, Luby JL, Barch DM. Child gain approach and loss avoidance behavior: relationships with depression risk, negative mood, and anhedonia. J Am Acad Child Adolesc Psychiatry. 2015;54:643–51.
Boger KD, Auerbach RP, Pechtel P, Busch AB, Greenfield SF, Pizzagalli DA. Co-occurring depressive and substance use disorders in adolescents: an examination of reward responsiveness during treatment. J Psychother Integr. 2014;24:109–21.
Insel TR, Gogtay N. National Institute of Mental Health clinical trials: new opportunities, new expectations. JAMA Psychiatry. 2014;71:745–6.
Dichter GS, Felder JN, Petty C, Bizzell J, Ernst M, Smoski MJ. The effects of psychotherapy on neural responses to rewards in major depression. Biol Psychiatry. 2009;66:886–97.
Burkhouse KL, Kujawa A, Kennedy AE, Shankman SA, Langenecker SA, Phan KL, et al. Neural reactivity to reward as a predictor of cognitive behavioral therapy response in anxiety and depression. Depress Anxiety. 2016;33:281–8.
Burkhouse KL, Gorka SM, Klumpp H, Kennedy AE, Karich S, Francis J, et al. Neural responsiveness to reward as an index of depressive symptom change following cognitive-behavioral therapy and selective serotonin reuptake inhibitor treatment. J Clin Psychiatry. 2018;79:17m11836.
Cheavens JS, Strunk DR, Lazarus SA, Goldstein LA. The compensation and capitalization models: a test of two approaches to individualizing the treatment of depression. Behav Res Ther. 2012;50:699–706.
Norris LA, Rabner JC, Mennies RJ, Olino TM, Kendall PC. Increased self-reported reward responsiveness predicts better response to cognitive behavioral therapy for youth with anxiety. J Anxiety Disord. 2021;80:102402.
Sequeira SL, Silk JS, Ladouceur CD, Hanson JL, Ryan ND, Morgan JK, et al. Association of neural reward circuitry function with response to psychotherapy in youths with anxiety disorders. Am J Psychiatry. 2021;178:343–51.
Sauer-Zavala S, Cassiello-Robbins C, Ametaj AA, Wilner JG, Pagan D. Transdiagnostic treatment personalization: the feasibility of ordering unified protocol modules according to patient strengths and weaknesses. Behav Modif. 2019;43:518–43.
Kaufman J, Birmaher B, Brent D, Rao U, Flynn C, Moreci P, et al. Schedule for affective disorders and schizophrenia for school-age children-present and lifetime version (K-SADS-PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry. 1997;36:980–8.
de Bie HMA, Boersma M, Wattjes MP, Adriaanse S, Vermeulen RJ, Oostrom KJ, et al. Preparing children with a mock scanner training protocol results in high quality structural and functional MRI scans. Eur J Pediatr. 2010;169:1079–85.
Forbes EE, Olino TM, Ryan ND, Birmaher B, Axelson D, Moyles DL, et al. Reward-related brain function as a predictor of treatment response in adolescents with major depressive disorder. Cogn Affect Behav Neurosci. 2010;10:107–18.
Olino TM, McMakin DL, Morgan JK, Silk JS, Birmaher B, Axelson DA, et al. Reduced reward anticipation in youth at high-risk for unipolar depression: a preliminary study. Dev Cogn Neurosci. 2014;8:55–64.
Forbes EE, Hariri AR, Martin SL, Silk JS, Moyles DL, Fisher PM, et al. Altered striatal activation predicting real-world positive affect in adolescent major depressive disorder. Am J Psychiatry. 2009;166:64–73.
Forbes EE, Stepp SD, Dahl RE, Ryan ND, Whalen D, Axelson DA, et al. Real-world affect and social context as predictors of treatment response in child and adolescent depression and anxiety: an ecological momentary assessment study. J Child Adolesc Psychopharmacol. 2012;22:37–47.
Webb CA, Israel ES, Belleau E, Appleman L, Forbes EE, Pizzagalli DA. Mind-wandering in adolescents predicts worse affect and is linked to aberrant default mode network–salience network connectivity. J Am Acad Child Adolesc Psychiatry. 2021;60:377–87.
Radloff LS. The CES-D scale a self-report depression scale for research in the general population. Appl Psychol Meas. 1977;1:385–401.
Manos RC, Kanter JW, Luo W. The behavioral activation for depression scale–short form: development and validation. Behav Ther. 2011;42:726–39.
Laurent J, Catanzaro SJ, Joiner TE Jr., Rudolph KD, Potter KI, Lambert S, et al. A measure of positive and negative affect for children: scale development and preliminary validation. Psychol Assess. 1999;11:326–38.
Bates D, Mächler M, Bolker B, Walker S. Fitting linear mixed-effects models using lme4. J Statistical Softw. 2014;67:1–48.
Kuznetsova A, Brockhoff PB, Christensen RHB. lmerTest package: tests in linear mixed effects models. J Stat Softw. 2017;82:1–26.
Trøstheim M, Eikemo M, Meir R, Hansen I, Paul E, Kroll SL, et al. Assessment of anhedonia in adults with and without mental illness: a systematic review and meta-analysis. JAMA Netw Open. 2020;3:e2013233.
Positive valence systems: workshop proceedings. National Institute of Mental Health NIMH. https://www.nimh.nih.gov/research/research-funded-by-nimh/rdoc/positive-valence-systems-workshop-proceedings. Accessed 20 June 2022.
Treadway MT, Buckholtz JW, Schwartzman AN, Lambert WE, Zald DH. Worth the ‘EEfRT’? The effort expenditure for rewards task as an objective measure of motivation and anhedonia. PLOS One. 2009;4:e6598.
Saxena A, Luking KR, Barch DM, Pagliaccio D. Individual differences in hedonic capacity, depressed mood, and affective states predict emotional reactivity. Motiv Emot. 2017;41:419–29.
Dowd EC, Barch DM. Anhedonia and emotional experience in schizophrenia: neural and behavioral indicators. Biol Psychiatry. 2010;67:902–11.
Burbridge JA, Barch DM. Anhedonia and the experience of emotion in individuals with schizophrenia. J Abnorm Psychol. 2007;116:30–42.
Watson R, Harvey K, McCabe C, Reynolds S. Understanding anhedonia: a qualitative study exploring loss of interest and pleasure in adolescent depression. Eur Child Adolesc Psychiatry. 2020;29:489–99.
Funding
This research was supported by NIMH K23MH108752 (CW). CW was partially supported by NIMH R01MH116969, NCCIH R01AT011002, the Tommy Fuss Fund and a NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation. LM was supported by a grant from the National Institute of Drug Abuse (NIDA; T32 DA015036; PI: Dr. Lukas). DAP was partially supported by R37 MH068376, Wellcome Leap and by a Distinguished Investigator Award from the Brain and Behavior Research Foundation. EEF was supported by NIH R01 MH104418 and NIH R01 MH124900. The content is solely the responsibility of the author and does not necessarily represent the official views of NIH, Wellcome Leap or the Brain & Behavior Research Foundation.
Author information
Authors and Affiliations
Contributions
CW acquired funding for the project. CW, DP, and EF conceptualized the study. CW, AT, and LM acquired, processed, and analyzed the data. All authors contributed to interpretation of findings and drafting the manuscript. All authors approved the final version of the manuscript.
Corresponding author
Ethics declarations
Competing interests
Over the past 3 years, DAP has received consulting fees from Albright Stonebridge Group, Boehringer Ingelheim, Compass Pathways, Engrail Therapeutics, Neumora Therapeutics (formerly BlackThorn Therapeutics), Neurocrine Biosciences, Neuroscience Software, Otsuka, Sunovion, and Takeda; he has received honoraria from the Psychonomic Society and the American Psychological Association (both for editorial work) as well as Alkermes; he has received research funding from the Brain and Behavior Research Foundation, the Dana Foundation, Millennium Pharmaceuticals, and NIMH; he has received stock options from Compass Pathways, Engrail Therapeutics, Neumora Therapeutics, and Neuroscience Software; he has a financial interest in Neumora Therapeutics (formerly BlackThorn Therapeutics), which has licensed the copyright to the probabilistic reward task through Harvard University. DAP’s interests were reviewed and are managed by McLean Hospital and Partners HealthCare in accordance with their conflict of interest policies. DAP is on the editorial board of Neuropsychopharmacology. In the past 3 years, EEF received an honorarium from Society for Psychological Science for editing. No funding from these entities was used to support the current work, and all views expressed are solely those of the authors. The other authors declare no competing interests.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Webb, C.A., Murray, L., Tierney, A.O. et al. Reward-related predictors of symptom change in behavioral activation therapy for anhedonic adolescents: a multimodal approach. Neuropsychopharmacol. 48, 623–632 (2023). https://doi.org/10.1038/s41386-022-01481-4
Received:
Revised:
Accepted:
Published:
Version of record:
Issue date:
DOI: https://doi.org/10.1038/s41386-022-01481-4
This article is cited by
-
Posttraumatic stress, anxiety, and depression in mothers after preterm delivery and the associated psychological processes
BMC Pregnancy and Childbirth (2025)
-
Multimodal prediction of future depressive symptoms in adolescents
BMC Psychiatry (2025)
-
Brain connectivity and transcriptional changes induced by rTMS in first-episode major depressive disorder
Translational Psychiatry (2025)
-
Prediction of generalized anxiety disorder treatment outcomes with neurobehavioral responses to approach-avoidance conflict: a randomized clinical trial
Translational Psychiatry (2025)
-
Measuring activation during behavioral activation therapy: a proof-of-concept study using smartphone sensors and LLM-derived ratings in adolescents with anhedonia
NPP—Digital Psychiatry and Neuroscience (2025)
