Ignite Creation Date:
2026-03-26 @ 3:16 PM
Ignite Modification Date:
2026-03-31 @ 1:41 AM
Study NCT ID:
NCT07388004
Status:
RECRUITING
Last Update Posted:
2026-02-10
First Post:
2025-12-08
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Group Therapy for Major Depression: Comparing Expectation-Focused and Reward-Focused Psychotherapy Approaches
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2026-03-25'}, 'conditionBrowseModule': {'meshes': [{'id': 'D003865', 'term': 'Depressive Disorder, Major'}], 'ancestors': [{'id': 'D003866', 'term': 'Depressive Disorder'}, {'id': 'D019964', 'term': 'Mood Disorders'}, {'id': 'D001523', 'term': 'Mental Disorders'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'SINGLE', 'whoMasked': ['OUTCOMES_ASSESSOR'], 'maskingDescription': 'Independent outcome assessors conducting clinician-rated measures (e.g., HAMD-21) will remain blinded to group allocation. Participants, therapists, and investigators are not blinded.'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Participants will be randomly assigned in equal proportions to one of three parallel groups: EFPI, REACT, or waiting-list control.'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 150}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2025-10-13', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2026-02', 'completionDateStruct': {'date': '2028-06-30', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2026-02-05', 'studyFirstSubmitDate': '2025-12-08', 'studyFirstSubmitQcDate': '2026-01-27', 'lastUpdatePostDateStruct': {'date': '2026-02-10', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2026-02-04', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2027-12-31', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Change in Depressive Symptoms (Beck Depression Inventory-II)', 'timeFrame': 'Baseline, post-treatment (5 weeks), 3-month and 6-month follow-ups', 'description': 'Change in depressive symptom severity assessed with the Beck Depression Inventory-II (BDI-II), a 21-item self-report questionnaire measuring cognitive, affective, and somatic symptoms of depression.\n\nTotal scores range from 0 to 63, with higher scores indicating more severe depressive symptoms.\n\nThe primary endpoint is the change from baseline to post-treatment (5 weeks). Symptom stability and maintenance will be examined at follow-up assessments.'}], 'secondaryOutcomes': [{'measure': 'Change in Depressive Symptoms (Hamilton Depression Rating Scale, 21-item)', 'timeFrame': 'Baseline and post-treatment (5 weeks)', 'description': 'Change in clinician-rated depressive symptom severity assessed with the Hamilton Depression Rating Scale (HAMD-21), administered by trained, blinded assessors.\n\nTotal scores range from 0 to 64, with higher scores indicating more severe depressive symptoms.'}, {'measure': 'Depressive Expectations (Depressive Expectations Scale)', 'timeFrame': 'Baseline, post-treatment (5 weeks), 3-month and 6-month follow-ups', 'description': 'Change in depressive expectations assessed with the Depressive Expectations Scale (DES), a self-report questionnaire measuring negative, situation-specific expectations related to mood regulation, social interactions, performance, and coping. Items are rated on a 5-point Likert scale; higher scores indicate more negative and dysfunctional expectations.'}, {'measure': 'Hopelessness (Beck Hopelessness Scale)', 'timeFrame': 'Baseline, post-treatment (5 weeks), 3-month and 6-month follow-ups', 'description': 'Change in hopelessness assessed with the Beck Hopelessness Scale (BHS), a 20-item self-report questionnaire measuring negative expectations about the future.\n\nTotal scores range from 0 to 20, with higher scores indicating greater hopelessness.'}, {'measure': 'Socially Negative Expectations (Social Anxiety-Negative Beliefs Scale, SANB-5)', 'timeFrame': 'Baseline, post-treatment (5 weeks), 3-month and 6-month follow-ups', 'description': 'Change in negative social expectations assessed with the Social Anxiety-Negative Beliefs Scale (SANB-5), a 5-item self-report measure capturing fears of negative evaluation and rejection in social contexts.\n\nItems are rated on a 4-point Likert scale; higher scores indicate stronger negative social expectations.'}, {'measure': 'Behavioral Activation and Reward Responsiveness (Behavioral Activation System Scale)', 'timeFrame': 'Baseline, post-treatment (5 weeks), 3-month and 6-month follow-ups', 'description': 'Change in reward responsiveness assessed with the Behavioral Activation System (BAS) Scale, a self-report questionnaire measuring approach motivation, reward sensitivity, and positive affective reactivity.\n\nItems are rated on a 4-point Likert scale; higher scores indicate greater behavioral activation and reward sensitivity.'}, {'measure': 'Resilience (Resilience Scale, RS-25)', 'timeFrame': 'Baseline, post-treatment (5 weeks), 3-month and 6-month follow-ups', 'description': 'Change in psychological resilience assessed with the Resilience Scale (RS-25), a 25-item self-report questionnaire measuring personal competence, acceptance of self and life, and adaptive functioning.\n\nItems are rated on a 7-point Likert scale; higher scores indicate greater resilience.'}, {'measure': 'General Self-Efficacy (Allgemeine Selbstwirksamkeit Kurzskala, ASKU)', 'timeFrame': 'Baseline, post-treatment (5 weeks), 3-month and 6-month follow-ups', 'description': "Change in perceived self-efficacy assessed with the General Self-Efficacy Short Scale (ASKU), a 3-item self-report measure of confidence in one's ability to cope with difficult situations.\n\nItems are rated on a 5-point scale; higher scores indicate greater self-efficacy."}, {'measure': 'Treatment Expectations and Experiences (Generic Expectation Evaluation Questionnaire)', 'timeFrame': 'Baseline, post-treatment (5 weeks), 3-month and 6-month follow-ups', 'description': 'Treatment-related expectations and experiences assessed with the Generic Expectation Evaluation Questionnaire (G-EEE), including expected symptom improvement, worsening, and side effects prior to treatment, as well as perceived changes during and after treatment.\n\nRatings are provided on numerical rating scales from 0 to 10, with higher scores indicating stronger expectations or perceived effects.'}, {'measure': 'Suicidal Ideation and Behavior (Suicide Behaviors Questionnaire-Revised)', 'timeFrame': 'Baseline, post-treatment (5 weeks), 3-month and 6-month follow-ups', 'description': 'Suicidal ideation and behavior assessed with the Suicide Behaviors Questionnaire-Revised (SBQ-R), a 4-item self-report screening instrument covering lifetime suicidal ideation and attempts, frequency of ideation, threat of attempt, and self-assessed likelihood of future suicide.\n\nItem responses are recoded and summed to yield a total score ranging from 3 to 18; higher scores indicate greater suicide risk.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Major Depressive Disorder', 'Psychotherapy', 'Group Therapy', 'Expectation Violation', 'Reward Sensitivity', 'Mechanism-Based Intervention', 'Randomized Clinical Trial'], 'conditions': ['Major Depressive Disorder (MDD)']}, 'referencesModule': {'references': [{'pmid': '20603146', 'type': 'BACKGROUND', 'citation': 'Treadway MT, Zald DH. Reconsidering anhedonia in depression: lessons from translational neuroscience. Neurosci Biobehav Rev. 2011 Jan;35(3):537-55. doi: 10.1016/j.neubiorev.2010.06.006. Epub 2010 Jul 11.'}, {'pmid': '25415499', 'type': 'BACKGROUND', 'citation': 'Whitton AE, Treadway MT, Pizzagalli DA. Reward processing dysfunction in major depression, bipolar disorder and schizophrenia. Curr Opin Psychiatry. 2015 Jan;28(1):7-12. doi: 10.1097/YCO.0000000000000122.'}, {'pmid': '11861707', 'type': 'BACKGROUND', 'citation': 'Watkins E, Brown RG. Rumination and executive function in depression: an experimental study. J Neurol Neurosurg Psychiatry. 2002 Mar;72(3):400-2. doi: 10.1136/jnnp.72.3.400.'}, {'pmid': '17716046', 'type': 'BACKGROUND', 'citation': 'Kazdin AE. Mediators and mechanisms of change in psychotherapy research. Annu Rev Clin Psychol. 2007;3:1-27. doi: 10.1146/annurev.clinpsy.3.022806.091432.'}, {'pmid': '17074942', 'type': 'BACKGROUND', 'citation': 'Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, Niederehe G, Thase ME, Lavori PW, Lebowitz BD, McGrath PJ, Rosenbaum JF, Sackeim HA, Kupfer DJ, Luther J, Fava M. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006 Nov;163(11):1905-17. doi: 10.1176/ajp.2006.163.11.1905.'}, {'pmid': '28069021', 'type': 'BACKGROUND', 'citation': 'Rief W, Shedden-Mora MC, Laferton JA, Auer C, Petrie KJ, Salzmann S, Schedlowski M, Moosdorf R. Preoperative optimization of patient expectations improves long-term outcome in heart surgery patients: results of the randomized controlled PSY-HEART trial. BMC Med. 2017 Jan 10;15(1):4. doi: 10.1186/s12916-016-0767-3.'}, {'pmid': '28498580', 'type': 'BACKGROUND', 'citation': 'Rief W, Anna Glombiewski J. The role of expectations in mental disorders and their treatment. World Psychiatry. 2017 Jun;16(2):210-211. doi: 10.1002/wps.20427. No abstract available.'}, {'pmid': '37667190', 'type': 'BACKGROUND', 'citation': 'Potsch L, Rief W. Transdiagnostic considerations of the relationship between reward sensitivity and psychopathological symptoms - a cross-lagged panel analysis. BMC Psychiatry. 2023 Sep 4;23(1):650. doi: 10.1186/s12888-023-05139-3.'}, {'pmid': '35775159', 'type': 'BACKGROUND', 'citation': 'Pizzagalli DA. Toward a Better Understanding of the Mechanisms and Pathophysiology of Anhedonia: Are We Ready for Translation? Am J Psychiatry. 2022 Jul;179(7):458-469. doi: 10.1176/appi.ajp.20220423.'}, {'pmid': '24471371', 'type': 'BACKGROUND', 'citation': 'Pizzagalli DA. Depression, stress, and anhedonia: toward a synthesis and integrated model. Annu Rev Clin Psychol. 2014;10:393-423. doi: 10.1146/annurev-clinpsy-050212-185606.'}, {'pmid': '35582783', 'type': 'BACKGROUND', 'citation': 'Pan PM, Sato JR, Paillere Martinot ML, Martinot JL, Artiges E, Penttila J, Grimmer Y, van Noort BM, Becker A, Banaschewski T, Bokde ALW, Desrivieres S, Flor H, Garavan H, Ittermann B, Nees F, Papadopoulos Orfanos D, Poustka L, Frohner JH, Whelan R, Schumann G, Westwater ML, Grillon C, Cogo-Moreira H, Stringaris A, Ernst M; IMAGEN Consortium. Longitudinal Trajectory of the Link Between Ventral Striatum and Depression in Adolescence. Am J Psychiatry. 2022 Jul;179(7):470-481. doi: 10.1176/appi.ajp.20081180. Epub 2022 May 18.'}, {'pmid': '31515055', 'type': 'BACKGROUND', 'citation': 'Kube T, Schwarting R, Rozenkrantz L, Glombiewski JA, Rief W. Distorted Cognitive Processes in Major Depression: A Predictive Processing Perspective. Biol Psychiatry. 2020 Mar 1;87(5):388-398. doi: 10.1016/j.biopsych.2019.07.017. Epub 2019 Jul 29.'}, {'pmid': '30131084', 'type': 'BACKGROUND', 'citation': 'Kube T, Rief W, Gollwitzer M, Gartner T, Glombiewski JA. Why dysfunctional expectations in depression persist - Results from two experimental studies investigating cognitive immunization. Psychol Med. 2019 Jul;49(9):1532-1544. doi: 10.1017/S0033291718002106. Epub 2018 Aug 22.'}, {'pmid': '39186743', 'type': 'BACKGROUND', 'citation': 'Kirchner L, Rief W, Muller L, Buchwald H, Fuhrmann K, Berg M. Depressive symptoms and the processing of unexpected social feedback: Differences in surprise levels, feedback acceptance, and "immunizing" cognition. PLoS One. 2024 Aug 26;19(8):e0307035. doi: 10.1371/journal.pone.0307035. eCollection 2024.'}, {'pmid': '25931539', 'type': 'BACKGROUND', 'citation': 'Insel TR, Cuthbert BN. Medicine. Brain disorders? Precisely. Science. 2015 May 1;348(6234):499-500. doi: 10.1126/science.aab2358. No abstract available.'}, {'pmid': '23459093', 'type': 'BACKGROUND', 'citation': 'Hofmann SG, Asnaani A, Vonk IJ, Sawyer AT, Fang A. The Efficacy of Cognitive Behavioral Therapy: A Review of Meta-analyses. Cognit Ther Res. 2012 Oct 1;36(5):427-440. doi: 10.1007/s10608-012-9476-1. Epub 2012 Jul 31.'}, {'pmid': '26183698', 'type': 'BACKGROUND', 'citation': 'Greenberg T, Chase HW, Almeida JR, Stiffler R, Zevallos CR, Aslam HA, Deckersbach T, Weyandt S, Cooper C, Toups M, Carmody T, Kurian B, Peltier S, Adams P, McInnis MG, Oquendo MA, McGrath PJ, Fava M, Weissman M, Parsey R, Trivedi MH, Phillips ML. Moderation of the Relationship Between Reward Expectancy and Prediction Error-Related Ventral Striatal Reactivity by Anhedonia in Unmedicated Major Depressive Disorder: Findings From the EMBARC Study. Am J Psychiatry. 2015 Sep 1;172(9):881-91. doi: 10.1176/appi.ajp.2015.14050594. Epub 2015 Jul 17.'}, {'pmid': '20068583', 'type': 'BACKGROUND', 'citation': 'Friston K. The free-energy principle: a unified brain theory? Nat Rev Neurosci. 2010 Feb;11(2):127-38. doi: 10.1038/nrn2787. Epub 2010 Jan 13.'}, {'pmid': '25879936', 'type': 'BACKGROUND', 'citation': "Fried EI, Nesse RM. Depression sum-scores don't add up: why analyzing specific depression symptoms is essential. BMC Med. 2015 Apr 6;13:72. doi: 10.1186/s12916-015-0325-4."}, {'pmid': '36280262', 'type': 'BACKGROUND', 'citation': 'Ferrari A, Richter D, de Lange FP. Updating Contextual Sensory Expectations for Adaptive Behavior. J Neurosci. 2022 Nov 23;42(47):8855-8869. doi: 10.1523/JNEUROSCI.1107-22.2022. Epub 2022 Oct 24.'}, {'pmid': '29934355', 'type': 'BACKGROUND', 'citation': 'Fazeli S, Buchel C. Pain-Related Expectation and Prediction Error Signals in the Anterior Insula Are Not Related to Aversiveness. J Neurosci. 2018 Jul 18;38(29):6461-6474. doi: 10.1523/JNEUROSCI.0671-18.2018. Epub 2018 Jun 22.'}, {'pmid': '36948546', 'type': 'BACKGROUND', 'citation': 'Ewen AI, Bleichhardt G, Rief W, Von Blanckenburg P, Wambach K, Wilhelm M. Expectation focused and frequency enhanced cognitive behavioural therapy for patients with major depression (EFFECT): a study protocol of a randomised active-control trial. BMJ Open. 2023 Mar 22;13(3):e065946. doi: 10.1136/bmjopen-2022-065946.'}, {'pmid': '28804467', 'type': 'BACKGROUND', 'citation': "D'Astolfo L, Rief W. Learning about Expectation Violation from Prediction Error Paradigms - A Meta-Analysis on Brain Processes Following a Prediction Error. Front Psychol. 2017 Jul 28;8:1253. doi: 10.3389/fpsyg.2017.01253. eCollection 2017."}, {'pmid': '36640411', 'type': 'BACKGROUND', 'citation': 'Cuijpers P, Miguel C, Harrer M, Plessen CY, Ciharova M, Ebert D, Karyotaki E. Cognitive behavior therapy vs. control conditions, other psychotherapies, pharmacotherapies and combined treatment for depression: a comprehensive meta-analysis including 409 trials with 52,702 patients. World Psychiatry. 2023 Feb;22(1):105-115. doi: 10.1002/wps.21069.'}, {'pmid': '24679399', 'type': 'BACKGROUND', 'citation': 'Cuijpers P, Karyotaki E, Weitz E, Andersson G, Hollon SD, van Straten A. The effects of psychotherapies for major depression in adults on remission, recovery and improvement: a meta-analysis. J Affect Disord. 2014 Apr;159:118-26. doi: 10.1016/j.jad.2014.02.026. Epub 2014 Feb 24.'}, {'pmid': '24387236', 'type': 'BACKGROUND', 'citation': 'Beck AT, Haigh EA. Advances in cognitive theory and therapy: the generic cognitive model. Annu Rev Clin Psychol. 2014;10:1-24. doi: 10.1146/annurev-clinpsy-032813-153734. Epub 2014 Jan 2.'}], 'seeAlsoLinks': [{'url': 'https://www.who.int/news-room/fact-sheets/detail/mental-health-at-work', 'label': 'World Health Organization. (2023). Mental health at work. WHO.'}]}, 'descriptionModule': {'briefSummary': 'Major depressive disorder (MDD) is one of the most common psychiatric conditions and often remains difficult to treat effectively. Many patients continue to experience residual symptoms or relapse even after receiving established forms of psychotherapy. This study tests whether targeting specific psychological mechanisms can improve outcomes for people with depression. We compare two novel group therapies: (1) Expectation-Focused Psychotherapeutic Intervention (EFPI), which aims to modify rigid, negative expectations that maintain depressive symptoms, and (2) Reward Enhancement and Activation Therapy (REACT), which focuses on increasing sensitivity to positive experiences and strengthening reward-related learning. Both are delivered in a group format to foster peer support and shared learning.\n\nA total of 150 adults with a current MDD diagnosis will be randomly assigned to EFPI, REACT, or a waiting-list control. Participants in the intervention groups receive 10 group sessions over five weeks. Waiting-list participants complete baseline and 3-month follow-up assessments before being offered standard treatment options.\n\nClinical outcomes are assessed at baseline, immediately after treatment, and at 3- and 6-month follow-ups (for the intervention groups). Primary outcomes are reductions in depressive symptoms measured by clinician ratings and self-report questionnaires. Secondary outcomes include changes in expectation processes and reward sensitivity.\n\nIn addition, functional MRI (fMRI) tasks examine brain mechanisms related to expectation updating and reward processing pre- and post-intervention, to help identify neural changes that may underlie symptom improvement.\n\nBy directly addressing dysfunctional expectations and reduced reward sensitivity, this study seeks to provide evidence for more targeted psychotherapeutic approaches. If successful, the results may support more personalized treatments and better long-term outcomes in MDD.', 'detailedDescription': 'Major depressive disorder (MDD) remains a leading cause of disability and often shows incomplete response or relapse after established treatments. A promising strategy is to move beyond broad, symptom-focused interventions toward therapies that directly target the psychological and neurobiological mechanisms maintaining depression. This trial evaluates two mechanism-based, group-delivered psychotherapies that each target a core process implicated in MDD: maladaptive expectation processing and reduced reward sensitivity.\n\nRationale and mechanistic framework. Expectation pathway. Predictive coding accounts propose that the brain continuously updates prior beliefs in light of new information. In depression, negative expectations about the self, others, and the future often become rigid and resistant to change. Cognitive immunization-discounting or reframing disconfirming evidence-prevents adaptive belief updating, maintains symptoms, and can weaken responses to conventional cognitive-behavioral interventions. Targeting dysfunctional expectations directly-via structured behavioral experiments that produce positive expectation violations and procedures that reduce cognitive immunization-may restore flexibility in belief revision and enhance treatment effects.\n\nReward pathway. Depressed patients frequently show reduced reward sensitivity, including blunted anticipation of reward and impaired reinforcement learning, processes linked to mesolimbic dopaminergic circuitry (e.g., ventral striatum/nucleus accumbens). These deficits can limit the benefit of nonspecific activity scheduling, which increases exposure to potentially rewarding situations but does not specifically remediate anticipatory and learning-related components of reward processing. Interventions that systematically enhance reward sensitivity and strengthen reinforcement contingencies may therefore improve motivational drive and positive affect.\n\nNeurobiological component. Expectation updating has been associated with activity in the dorsolateral prefrontal cortex (DLPFC) and anterior insula, whereas reward processing consistently engages the ventral striatum and insular cortex. This trial includes a functional MRI (fMRI) module to probe these mechanisms pre- and post-intervention. Participants perform established paradigms tapping threat/expectation learning, future-directed thinking, and social reward/expectation. Linking neural responses to clinical change will clarify how mechanism-based therapies exert their effects and may inform biomarkers for treatment selection and monitoring.\n\nStudy design overview. This is a randomized, controlled, superiority trial with three parallel groups: (1) EFPI, (2) REACT, and (3) waiting-list control. The trial follows a 3 × 5 repeated-measures design with planned assessments at baseline (pre-treatment), post-treatment (after 5 weeks), and 3- and 6-month follow-ups. Intervention groups complete all follow-ups; after the 6-month assessment they may initiate further treatment if desired. Waiting-list participants complete baseline and the 3-month follow-up before being ethically permitted to access other treatments. They continue to receive follow-up questionnaires at later time points, including items on additional treatments, to enable sensitivity analyses.\n\nRandomization is performed at the individual level with a 1:1:1 allocation ratio. Allocation is managed through secure electronic data capture to ensure concealment until assignment. Given the nature of group psychotherapy, participants and therapists are not blinded; however, outcome assessors remain blind to group allocation, and standardized procedures are applied for clinician-rated measures. Because treatment is delivered in groups, potential therapist- and group-related effects are monitored and considered analytically.\n\nInterventions (concise). EFPI and REACT are manualized group interventions delivered in 10 sessions over five weeks (two 100-minute sessions per week) by trained CBT therapists under regular supervision.\n\n* EFPI targets maladaptive expectations and cognitive immunization through psychoeducation; identification/documentation of negative expectations; structured real-life behavioral experiments (predict-test-experience-reflect); guided cognitive integration to promote flexible belief updating; and maintenance strategies.\n* REACT targets reduced reward sensitivity through systematic reinforcement procedures: identifying reward deficits and attentional biases; enhancing and prolonging positive experiences (e.g., savoring, imagery); structured engagement in meaningful rewarding activities with explicit reinforcement plans; and relapse-prevention strategies to sustain reward engagement.\n\nTherapist training, supervision, adherence checklists, and standardized materials support fidelity. The waiting-list control receives no active group intervention during the first three months but is offered standard treatment options thereafter.\n\nAssessments and timeline (overview). Clinical and behavioral data are collected at baseline, post-treatment, 3- and 6-month follow-ups in the intervention arms; the waiting-list control is assessed at baseline and 3 months prior to accessing further care. Digital data capture (e.g., REDCap) includes automated range and plausibility checks; follow-ups are facilitated via secure online questionnaires and structured telephone contacts to minimize attrition. In addition to clinician- and self-rated depression severity, the battery includes validated measures of expectation processing, reward sensitivity (anticipatory and learning components), and related cognitive-emotional constructs. Eligibility criteria and outcome measures are specified elsewhere in this record.\n\nNeuroimaging component (overview). An fMRI module is acquired at baseline and post-intervention (or the matched 3-month time point for the waiting-list group) to assay neural correlates of expectation updating and reward processing. Paradigms include: (i) conditioning-based tasks probing threat expectancy and expectation violation; (ii) future-directed thinking tasks eliciting positive/negative prospective/retrospective imagery; and (iii) a social reward/expectation paradigm using structured interactions with virtual partners. Region-of-interest analyses focus on DLPFC/anterior insula (expectation) and ventral striatum/insula (reward); whole-brain and connectivity analyses complement ROI findings. Standard preprocessing (e.g., motion correction, normalization, smoothing) and task-based GLMs with multiple-comparison control are used. Neuroimaging endpoints are related to clinical trajectories to test mechanistic hypotheses.\n\nAdherence, concomitant care, and retention. Participants confirm availability for the 5-week schedule before enrollment; attendance is monitored and automated reminders are sent. During the 5-week intervention phase, participants are asked to maintain stable psychotropic medication and to refrain from initiating additional psychotherapy; deviations are documented. After the intervention, participants may seek external psychotherapy; additional treatments at follow-up are recorded for sensitivity/covariate analyses. Retention is supported through reminders, flexible scheduling, and brief telephone assessments if full questionnaires are declined.\n\nSample size and operating characteristics. Planned enrollment is N = 150 (\\~50 per arm), allowing for expected attrition while preserving power to detect group × time effects of practical relevance in linear mixed-effects models. Power considerations were based on moderate effects from prior mechanism-focused psychotherapy literature; primary analyses will use linear mixed models.\n\nStatistical analysis (overview). Primary clinical analyses use linear mixed-effects models with fixed effects for Group, Time, and their interaction, and random intercepts (and where appropriate, random slopes) to account for within-subject dependency and between-subject heterogeneity. Models will consider therapist/group clustering where indicated. Prespecified mediation analyses test whether changes in expectation processing and reward sensitivity account for symptom change; moderation analyses examine whether baseline profiles predict differential benefit. Missing data are handled under missing-at-random assumptions using maximum likelihood, with multiple imputation in sensitivity analyses. Neuroimaging analyses relate pre-to-post changes in activation/connectivity to clinical improvements; ROI-based hypotheses are complemented by exploratory whole-brain analyses with appropriate error control.\n\nSafety monitoring and harms. Given the non-invasive, low-risk nature of group psychotherapy, no independent Data Safety Monitoring Board is planned. Safety is monitored by the investigative team throughout treatment and follow-up. Adverse events (including clinically significant symptom worsening or emergent suicidality) are documented and managed according to predefined procedures, with referral to appropriate care as needed and ethics notification when required. Criteria for discontinuation include persistent non-attendance or need for higher-level care during the intervention phase.\n\nData management and confidentiality. All data are pseudonymized (unique study IDs); identifying information is stored separately on access-restricted institutional servers. Electronic data capture uses role-based access, audit trails, and automated checks. After completion, personally identifying data are deleted; anonymized datasets are retained per policy and may be shared under GDPR-compliant agreements to support transparency and reproducibility.\n\nEthical conduct and dissemination. The protocol adheres to SPIRIT recommendations and has received ethics approval from the responsible institutional review board. Written informed consent is obtained from all participants prior to any study procedures. Results will be disseminated via peer-reviewed publications and scientific meetings; de-identified data and analysis code may be shared under controlled access agreements to promote open science.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '80 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Age: 18-80 years\n* Current diagnosis of major depressive disorder (MDD) according to DSM-5, confirmed by structured clinical interview (e.g., DIPS)\n* Hamilton Depression Rating Scale (HAMD-21) score ≥ 9\n* Ability to attend group therapy sessions (2×/week for 5 weeks)\n* Ability to undergo MRI scanning (for participants in the fMRI component) Written informed consent\n\nExclusion Criteria:\n\n* Current or lifetime diagnosis of bipolar disorder, psychotic disorder, or primary substance use disorder\n* High acute suicide risk requiring immediate intervention\n* Severe neurological disorder, brain injury, or contraindications for MRI (e.g., metal implants, claustrophobia)\n* Ongoing psychotherapy or initiation of a new antidepressant medication within the past 4 weeks\n* Insufficient German language proficiency to participate in therapy and complete study assessments\n* Cognitive impairment or other conditions interfering with informed consent or study participation'}, 'identificationModule': {'nctId': 'NCT07388004', 'acronym': 'PERSPECT', 'briefTitle': 'Group Therapy for Major Depression: Comparing Expectation-Focused and Reward-Focused Psychotherapy Approaches', 'organization': {'class': 'OTHER', 'fullName': 'Philipps University Marburg'}, 'officialTitle': 'Rewiring Expectations and Amplifying Rewards: A Study Protocol for a Randomized Controlled Trial of Mechanism-Based Group Psychotherapy for Major Depressive Disorder', 'orgStudyIdInfo': {'id': 'PERSPECT CRC393-C02'}, 'secondaryIdInfos': [{'id': '521379614', 'type': 'OTHER_GRANT', 'domain': 'German Research Foundation (Deutsche Forschungsgemeinschaft, DFG)'}, {'id': '23-272BO', 'type': 'OTHER', 'domain': 'Ethics Committee of Philipps-University Marburg'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Expectation-Focused Psychotherapeutic Intervention (EFPI)', 'description': 'Participants receive 10 group therapy sessions (2 sessions per week over 5 weeks) of EFPI, a mechanism-based psychotherapy targeting maladaptive expectations.\n\nThe intervention combines psychoeducation, structured behavioral experiments, and cognitive restructuring to systematically challenge negative expectations.\n\nA central focus is reducing cognitive immunization-the tendency to dismiss or reframe positive disconfirming evidence-to foster more flexible and adaptive belief updating.\n\nSessions are conducted in small groups (5-10 participants) to facilitate peer modeling, social reinforcement, and shared learning.\n\nThe first session includes baseline clinical assessments, and the final session includes immediate post-treatment assessments.\n\nAll participants are additionally followed up at 3 and 6 months after the intervention to evaluate the persistence of treatment effects.', 'interventionNames': ['Behavioral: Expectation-Focused Psychotherapeutic Intervention']}, {'type': 'EXPERIMENTAL', 'label': 'Reward Enhancement and Activation Therapy (REACT)', 'description': 'Participants receive 10 group therapy sessions (2 sessions per week over 5 weeks) of REACT, a mechanism-based psychotherapy designed to enhance reward sensitivity.\n\nCore intervention components include attentional retraining toward rewarding stimuli, savoring exercises to prolong positive affect, and structured reinforcement plans to strengthen motivation and engagement in rewarding activities.\n\nGroup discussions normalize difficulties in experiencing pleasure and provide strategies for sustaining rewarding behavior long-term.\n\nSessions are conducted in small groups (5-10 participants). The first session includes baseline assessments, and the final session includes immediate post-treatment assessments.\n\nLong-term outcomes are assessed through follow-up evaluations at 3- and 6-months post-intervention.', 'interventionNames': ['Behavioral: Reward Enhancement and Activation Therapy']}, {'type': 'NO_INTERVENTION', 'label': 'Waiting-List Control', 'description': 'Participants assigned to the waiting-list control condition do not receive active treatment during the initial 3-month period.\n\nThey complete baseline assessments at study entry and a follow-up assessment after 3 months, corresponding to the time frame of the active intervention arms.\n\nAfter the 3-month assessment, participants are ethically permitted to pursue standard care outside the study.\n\nFor comparability and long-term analyses, waiting-list participants continue to complete follow-up assessments at 6 months, including questions about any additional treatments received after the waiting-list phase.'}], 'interventions': [{'name': 'Expectation-Focused Psychotherapeutic Intervention', 'type': 'BEHAVIORAL', 'otherNames': ['EFPI'], 'description': 'EFPI is a manualized group psychotherapy for major depressive disorder that directly targets maladaptive expectations. The treatment integrates psychoeducation, cognitive restructuring, and behavioral experiments to modify negative expectancies and reduce cognitive immunization, thereby enhancing adaptive expectation updating.\n\nDelivery: Group format (5-10 participants), 10 sessions (twice weekly for 5 weeks).', 'armGroupLabels': ['Expectation-Focused Psychotherapeutic Intervention (EFPI)']}, {'name': 'Reward Enhancement and Activation Therapy', 'type': 'BEHAVIORAL', 'otherNames': ['REACT'], 'description': 'REACT is a manualized group psychotherapy for major depressive disorder that focuses on enhancing reward sensitivity and motivation. The intervention combines attentional retraining, savoring techniques, and reinforcement-based strategies to increase engagement with rewarding stimuli and experiences.\n\nDelivery: Group format (5-10 participants), 10 sessions (twice weekly for 5 weeks).', 'armGroupLabels': ['Reward Enhancement and Activation Therapy (REACT)']}]}, 'contactsLocationsModule': {'locations': [{'zip': '35032', 'city': 'Marburg', 'state': 'Hesse', 'status': 'RECRUITING', 'country': 'Germany', 'contacts': [{'name': 'Masia Fernanda Hoffmann, M.Sc.', 'role': 'CONTACT', 'email': 'fernanda.hoffmann@uni-marburg.de', 'phone': '+4917656538480'}, {'name': 'Lukas Kirchner, Dr.', 'role': 'CONTACT', 'email': 'lukas.kirchner@uni-giessen.de'}], 'facility': 'Philipps-University Marburg', 'geoPoint': {'lat': 50.80904, 'lon': 8.77069}}], 'centralContacts': [{'name': 'Masia Fernanda Hoffmann, M.Sc.', 'role': 'CONTACT', 'email': 'fernanda.hoffmann@uni-marburg.de', 'phone': '+4917656538480'}, {'name': 'Winfried Rief, Prof. Dr.', 'role': 'CONTACT', 'email': 'rief@staff.uni-marburg.de', 'phone': '+49 6421 282 3657'}], 'overallOfficials': [{'name': 'Winfried Rief, Prof. Dr.', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Philipps University Marburg'}]}, 'ipdSharingStatementModule': {'infoTypes': ['STUDY_PROTOCOL', 'SAP', 'ICF', 'ANALYTIC_CODE'], 'timeFrame': 'Data and supporting documents will be available within 12 months after publication of the primary outcomes and will remain accessible for at least 10 years thereafter.', 'ipdSharing': 'YES', 'description': 'De-identified individual participant data (IPD) will be made available upon reasonable request after publication of the main results, in accordance with DFG and CRC/TRR 393 data sharing policies. Data access will require a data use agreement and ethical approval.', 'accessCriteria': 'De-identified individual participant data (IPD), study protocol, statistical analysis plan, and informed consent form will be made available to qualified researchers upon reasonable request. Access will be provided via the Open Science Framework (OSF) project page once data are curated and anonymized. Requests for access can be directed to the principal investigators of Project C02 within the CRC/TRR 393. Data will be available for scientific use after publication of the main results.'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Philipps University Marburg', 'class': 'OTHER'}, 'collaborators': [{'name': 'German Research Foundation', 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR'}}}}