An interventional study of Targeted affective cognitive training in Major Depressive Disorder (MDD) and Bipolar Disorder (BD), sponsored by Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg Hospital. Recruiting at 1 site in Denmark. Open to participants aged 18 Years to 60 Years. Per ClinicalTrials.gov, last updated 2026-11-05.
Sponsored by Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg Hospital · Not applicable, Interventional, and Treatment
The aim of this clinical trial is to investigate the effects of a six-week targeted affective cognitive training, combining virtual reality and computer-based exercises, in symptomatically stable patients with mood disorders (major depressive disorder or bipolar disorder) and unaffected first-degree relatives.
The investigators hypothesize that targeted affective cognitive training, compared with treatment as usual, will improve affective cognition (primary outcome), assessed using a composite measure of emotion regulation and facial emotion recognition.
Secondly, the investigators hypothesize that the training will improve self-reported emotion regulation abilities and associated neural activity during emotion regulation, including changes in dorsolateral prefrontal cortex activity.
Finally, the investigators will explore whether the training affects broader cognitive functioning, psychosocial functioning, quality of life, and longer-term clinical outcomes, including relapse or onset of mood disorder.
The study will include adults aged 18-60 years with major depressive disorder or bipolar disorder who are in full or partial remission at inclusion, as well as unaffected first-degree relatives of individuals with mood disorders, with the sample enriched for individuals experiencing emotion regulation difficulties. Symptomatic stability is defined as a score of ≤14 on both the 17-item Hamilton Depression Rating Scale (HDRS-17) and the Young Mania Rating Scale (YMRS). To accommodate an approximated drop-out rate of 20% from baseline to treatment completion, the investigators will recruit up to 100 participants until full data sets are obtained for 80 participants (40 participants per arm).
Participants will be recruited through the outpatient Copenhagen Affective Disorder Clinic, other mental health centers in the Capital Region of Denmark, through consultant psychiatrists in the Capital Region and through advertisements on relevant websites. Potentially eligible participants will receive oral and written information about the study and provide written informed consent before undergoing screening and baseline assessments.
At baseline, participants will complete a comprehensive assessment of affective and non-affective cognition. Affective cognition will be assessed using measures of emotion processing and regulation, while non-affective cognition will be assessed across domains including working memory, executive functioning, attention, processing speed and verbal learning and memory. Participants will also complete questionnaires assessing emotion regulation difficulties, habitual emotion-regulation strategies, quality of life and other relevant clinical characteristics. Psychosocial functioning will be assessed using the Functioning Assessment Short Test. Clinical assessments will include the HDRS-17 and YMRS.
Participants will additionally undergo magnetic resonance imaging, including structural imaging, resting-state functional MRI and task-based functional MRI. The task-based paradigms assess emotion reactivity and regulation, processing of emotional faces, and working memory. Biological samples, including blood and hair samples, will be collected to explore potential biological correlates and predictors of treatment response.
Following baseline assessment, participants will be randomized in a 1:1 ratio to either a six-week targeted affective cognitive training program or treatment as usual. The cognitive training consists of 10 individually delivered sessions combining virtual reality scenarios and computer-based exercises. The training targets attention, executive functioning, emotion recognition, and cognitive reappraisal.
The primary outcome is change in an affective cognition composite comprising performance-based measures of emotion regulation and facial expression recognition. Secondary outcomes include changes in self-reported emotion regulation difficulties and dorsolateral prefrontal cortex activity during emotion regulation. Exploratory outcomes include changes in broader cognitive functioning, psychosocial functioning, quality of life and other neural and biological measures.
Cognitive assessments, clinical ratings, questionnaires, biological sampling and MRI assessments will be repeated 1 week after the intervention period. Longer-term follow-up assessments will be conducted at 6 and 24 months to explore psychosocial functioning and clinical outcomes, including relapse among participants with mood disorders and onset of psychiatric disorder among unaffected relatives.
Block randomization will be conducted using the automated randomization module in Research Electronic Data Capture (REDCap) based on an uploaded blocked randomization list stratified by age (\< or ≥ 35 years) and diagnosis (major depressive disorder, bipolar disorder or no diagnosis).
3,041 studies on the registry are indexed under Depressive Disorder, Major; 588 are open to participants now.
This study's planned enrollment of 100 is above the median of 79 across 2,530 interventional studies indexed under Depressive Disorder, Major.
Browse Depressive Disorder, Major studies →Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg Hospital is the lead sponsor of 19 studies on the registry; 7 are open to participants now.
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Exclusion Criteria:
Behavioral: Targeted affective cognitive training
A six-week targeted affective cognitive training program comprising 10 individual sessions. The training includes psychoeducation, virtual reality tasks, computer-based exercises and between-session assignments.
Affective cognitive composite measure
A composite score of affective cognition based on the following tests: the Social Scenarios Task (down-regulation of negative emotion), the VERA task (down-regulation of negative emotion) and the Facial Expression Recognition Task (discrimination accuracy and speed of facial expression recognition). Higher scores reflect better performance.
Time frame: Baseline and week 7 (treatment completion)
Dorsal prefrontal cortex activity during emotion regulation
Functional magnetic resonance imaging (fMRI) measure of brain activity in a dorsal prefrontal volume of interest during an emotion regulation task using IAPS pictures (down-regulation versus react to negative pictures).
Time frame: Baseline and week 7 (treatment completion)
Difficulties in Emotion Regulation Scale (DERS)
Questionnaire assessing self-rated emotion regulation difficulties. Lower scores reflect better outcome.
Time frame: Baseline, week 7 (treatment completion), 6 months (follow-up)
VERA
Virtual Reality task assessing emotion regulation. Score range 1-5 (lower scores reflect better outcome).
Time frame: Baseline and week 7
Social Scenarios Task
Computerized neuropsychological test assessing emotional reactivity and emotion regulation in positive and negative situations. Outcomes include emotion reactivity (score range 0-100, lower scores reflect better outcome) and dampening (score range 0-100, lower scores reflect better outcome).
Time frame: Baseline and week 7 (treatment completion)
Facial Expression Recognition Task (FERT)
Computerized neuropsychological test assessing emotion recognition. Outcomes include reaction time (no score range, lower scores reflect better performance) and hit rate (score range 0-1, higher scores reflect better performance).
Time frame: Baseline and week 7 (treatment completion)
Valence bias task
Computerized task assessing valence judgements of emotionally ambiguous and clearly valenced stimuli, including faces and scenes
Time frame: Baseline and week 7 (treatment completion)
Hamilton Depression Rating Scale (HDRS-17)
Rating inventory assessing depressive symptoms. Score range 0-52. Lower scores reflect better outcome.
Time frame: Baseline and week 7 (treatment completion)
Young Mania Rating Scale (YMRS)
Rating inventory assessing (hypo)manic symptoms. Score range 0-60. Lower scores reflect better outcome.
Time frame: Baseline and week 7 (treatment completion)
Functional Assessment Short Test (FAST)
Interview-based assessment of functional capacity. Score range 0-72. Lower scores reflect better outcome.
Time frame: Baseline and week 7 (treatment completion)
Neural activity during an implicit emotional face-processing task
Functional magnetic resonance imaging (fMRI) measure of brain activity during fearful and happy face processing
Time frame: Baseline and week 7 (treatment completion)
Neural activity during a verbal n-back task
Functional magnetic resonance imaging (fMRI) measure of brain activity during a working memory task
Time frame: Baseline and week 7 (treatment completion)
Neural activity during resting state
Functional magnetic resonance imaging (fMRI) measure of brain activity during resting state
Time frame: Baseline and week 7 (treatment completion)
Changes in brain structure
Structural magnetic resonance imaging (sMRI) measure of brain morphology, including regional brain volumes and cortical thickness
Time frame: Baseline and week 7 (treatment completion)
Wechsler Adult Intelligence Scale (WAIS)-III Letter-Number Sequencing
Neuropsychological test assessing working memory. Score range 0-21. Higher scores reflect better performance.
Time frame: Baseline and week 7 (treatment completion)
Trail Making Test A
Neuropsychological test assessing attention and processing speed. Scored as time to complete. Lower scores reflect better performance.
Time frame: Baseline and week 7 (treatment completion)
Trail Making Test B
Neuropsychological test assessing executive function. Scored as time to complete. Lower scores reflect better performance.
Time frame: Baseline and week 7 (treatment completion)
Verbal fluency with letters "S" and "D"
Neuropsychological test assessing executive functions. No score range. Higher scores reflect better performance.
Time frame: Baseline and week 7 (treatment completion)
Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Digit Span Test
Neuropsychological test assessing attention. Score range 0-16. Higher scores reflect better performance.
Time frame: Baseline and week 7 (treatment completion)
Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Coding
Neuropsychological test assessing psychomotor speed. Score range 0-89. Higher scores reflect better performance.
Time frame: Baseline and week 7 (treatment completion)
Rey Auditory Verbal Learning Test
Neuropsychological test assessing verbal memory. Outcomes include total recall (score range 0-75), immediate recall (score range 0-15), and delayed recall (score range 0-15). Higher scores reflect better performance.
Time frame: Baseline and week 7 (treatment completion)
Emotion Regulation Questionnaire-30 (ERQ-30)
Questionnaire on habitual emotion regulation strategies.
Time frame: Baseline and week 7 (treatment completion)
Attentional Control Scale
Questionnaire on perceived attentional control. Score range 20-80. Higher scores indicate better attentional control.
Time frame: Baseline and week 7 (treatment completion)
Work and Social Adjustment Scale (WSAS)
Questionnaire assessing occupational functioning. Score range 0-40. Higher scores reflect worse outcome.
Time frame: Baseline, week 7 (treatment completion), 6 months (follow-up)
Sheehan's Disability Scale (SDS)
Questionnaire assessing everyday functioning. Score range 0-30. Higher scores reflect worse outcome.
Time frame: Baseline, week 7 (treatment completion), 6 months (follow-up)
Cognitive Complaints in Bipolar Disorder Rating Scale (COBRA)
Questionnaire on subjective cognitive complaints. Score range 0-48. Higher scores means worse outcome
Time frame: Baseline and week 7 (treatment completion)
State-Trait Anxiety Inventory Questionnaire (STAI)
Questionnaire on state and trait anxiety. Each subscale ranges from 20-80. Higher scores indicate greater anxiety.
Time frame: Baseline and week 7 (treatment completion)
Metacognitions Questionnaire (MCQ-30)
Questionnaire on metacognitive beliefs. Score range 30-120. Higher scores indicate more maladaptive metacognitive beliefs.
Time frame: Baseline and week 7 (treatment completion)
European Quality of Life - 5 Dimensions (EQ-5D)
Questionnaire on health-related quality of life across five dimensions. Higher index scores indicate better health-related quality of life.
Time frame: Baseline and week 7 (treatment completion)
Metacognitive Knowledge and Experience
Ratings of perceived general cognitive functioning and memory performance. Score range -3 to +3, with higher scores indicating better perceived cognitive functioning.
Time frame: Baseline and week 7 (treatment completion)
Blood sample
Blood-based markers of inflammation and immune activity (C-reactive protein (CRP) and leukocytes)
Time frame: Baseline and week 7 (treatment completion)
Hair cortisol
Hair cortisol as index of long-term systemic cortisol levels
Time frame: Baseline and week 7 (treatment completion)
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Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg Hospital