Major Depressive Disorder
Conditions
Keywords
Rumination, Attention bias modification, Transdiagnostic
Brief summary
This study evaluates the effect of a computerized intervention for depressive symptoms called Affective Bias Modification (ABM). A third of the patients will receive active ABM, a third will receive sham ABM and a third will undergo assessment only. The study will investigate if rumination mediates the effect of the intervention and investigate if specific symptom profiles affect the effect of the intervention.
Detailed description
A main aim of the project is to investigate how the effects of an ABM intervention on depressive symptoms are mediated by transdiagnostic rumination and how characteristics of the symptom network moderate these effects. The Affective Bias Modification Task (ABM) will be applied in a randomized controlled, double blind clinical trial with 6 months follow-up. Personalized networks are generated from prospective assessment of depression-related processes at baseline and follow-ups. Patients (n = 150) will be recruited from out-patient clinics at Diakonhjemmet Hospital, and randomized into one of three conditions: active, sham and assessment only. Patients aged 18-65 with depression (major depressive disorder) or bipolar disorder 2, with or without comorbid anxiety and/or alcohol use disorder will be included. The main hypothesis is that subjects who are in the active ABM group will exhibit less tendency for stress related (state) rumination compared to those in the placebo group. Active vs placebo ABM will decrease depressive symptoms (6 months) and this effect will be mediated by the change in state rumination. Densely connected symptom network and high strength centrality of rumination at baseline will moderate the effect of ABM. By combining mechanisms research with a personalized symptom network approach, this study will be in the forefront of understanding how a drug-free treatment option works and for whom it works best.
Interventions
BEHAVIORALAffective bias modification
In the Affective bias modification (ABM) procedure, paired stimuli (e.g. a negative and a positive facial expression) are presented on a laptop screen, followed by one or two probes (dots) appearing in the spatial location of one of the stimuli. Participants are then required to press one of two buttons as quickly as possible to indicate the number of dots in the probe. Stimuli presentation time is 50% 500 ms and 50 % 1000 ms (evenly distributed throughout the task). In total, the ABM will comprise 90 trials of paired images of faces of different valences. In the active condition, the probe appears at the location of the most positive stimuli of each pair in 87 % of trials (encouraging a positive affective bias). Participants will do ABM in their homes (approx. 5 min.) twice a day for two weeks (28 sessions) using laptop computers provided by us.
BEHAVIORALSham Affective bias modification
In the Affective bias modification (ABM) procedure, paired stimuli (e.g. a negative and a positive facial expression) are presented on a laptop screen, followed by one or two probes (dots) appearing in the spatial location of one of the stimuli. Participants are then required to press one of two buttons as quickly as possible to indicate the number of dots in the probe. Stimuli presentation time is 50% 500 ms and 50 % 1000 ms (evenly distributed throughout the task). In total, the ABM will comprise 90 trials of paired images of faces of different valences. In the sham condition, the probe appears at the location of the most positive stimuli of each pair in 50 % of trials (no contingency between facial expressions shown and the probe location). Participants will do ABM in their homes (approx. 5 min.) twice a day for two weeks (28 sessions) using laptop computers provided by us.
Sponsors
Extrastiftelsen
Diakonhjemmet Hospital
University of Oxford
University of Oslo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
\- Current or remitted Major Depressive Disorder, with or without anxiety, with or without alcohol use disorder
Exclusion criteria
* Neurological disorder, mania, and/or psychosis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Self-reported Depressive Symptoms: Becks Depression Inventory-II | At 6 months follow-up | Self-reported depressive symptoms 6 months after the ABM intervention based on a 21-item scale. Each item is scored 0-3 (where scoring description is adapted to each item), yielding a score from 0-63. |
| State Rumination: Brief State Rumination Inventory (BSRI) | At baseline and two weeks follow up. | Change in self-reported state rumination after the stress induction from pre to post intervention on a 8 item scale. Difference score: BSRI post intervention - BRSI Baseline. A negative score means reduction in state rumination over the intervention. Each item is scored on a 0-100 Visual Analogue Scale. The total score divided by 8 to provide the mean item total score, hence the min= 0 and max = 100 for each of the BSRI assessment time points. It was hypothesized that change in state rumination over the intervention period would mediate the effect of ABM on depressive symptoms at six months follow up. |
| State Rumination: Brief State Rumination Inventory | At two weeks follow up. | Self-reported state rumination after stress induction on a 8 item scale. Each item is scored on a 0-100 Visual Analogue Scale, yielding a score from 0-800, which is reported divided by 8 to provide a mean total item score. Hence the min= 0 and max = 100. A higher score indicates more state rumination. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Affective Bias: Dot-probe Task | From baseline to two weeks follow up | Change in reaction time in milliseconds to probes in the location of the positive facial stimuli compared to probes in the location of the negative stimuli. Positive number implies reduction in negative bias. |
| Symptom Network Change: Experience Sampling of Depressive Symptoms | From two weeks prior to baseline to two weeks after the two-week intervention. | Changed centrality of rumination in networks estimated based on a 9-item experience sampling questionnaire of self-reported depressive symptoms scored on a 0-100 visual analogue scale (higher value, more symptoms; reversing interest, positive affect and activity; Kraft et al., 2023, Psychiatry Research Communications). Two person-specific networks (pre and post-intervention) were estimated using the var1-function in the R package psychonetrics, with full-information maximum likelihood estimator, based on the experience sampling questionnaires that were administrated 5 times/day for 14 days before and after the intervention. Centrality of rumination in these networks were calculated using qgraph (Epskamp et al., 2012) and standardized. Change in rumination centrality was calculated as difference between rumination centrality in the two estimated networks, and higher number indicate increased centrality of rumination (post-pre). |
| Symptom Network: Experience Sampling of Depressive Symptoms | Two weeks after the two-week intervention. | Centrality of rumination in networks based on a 9-item experience sampling questionnaire of self-reported depressive symptoms scored on a 0-100 visual analogue scale (higher value, more symptoms; reversing interest, positive affect and activity; Kraft et al., 2023, Psychiatry Research Communications). Person-specific networks were estimated using the var1-function in the R package psychonetrics, with full-information maximum likelihood estimator, based on the experience sampling questionnaires that were administrated 5 times/day for 14 days after the two-week intervention. Centrality of rumination in this network was calculated using qgraph (Epskamp et al., 2012) and standardized. Higher number indicate higher centrality of rumination. |
Countries
Norway
Participant flow
Recruitment details
Participants were recruited between Nov 19, 2019, and Aug 17, 2021 using local advertisements and social media. Entrance to the trial was via self-referral by phone or online registration.
Pre-assignment details
Did not meet the inclusion criteria (N=4), Declined to participate (n=4), Not able to get in contact with (N=4).
Participants by arm
| Arm | Count |
|---|---|
| Active Affective Bias Modification Computer based Affective Bias Modification
Affective bias modification: In the Affective bias modification (ABM) procedure, paired stimuli (e.g. a negative and a positive facial expression) are presented on a laptop screen, followed by one or two probes (dots) appearing in the spatial location of one of the stimuli. Participants are then required to press one of two buttons as quickly as possible to indicate the number of dots in the probe. Stimuli presentation time is 50% 500 ms and 50 % 1000 ms (evenly distributed throughout the task). In total, the ABM will comprise 90 trials of paired images of faces of different valences. In the active condition, the probe appears at the location of the most positive stimuli of each pair in 87 % of trials (encouraging a positive affective bias). Participants will do ABM in their homes (approx. 5 min.) twice a day for two weeks (28 sessions) using laptop computers provided by us. | 42 |
| Sham Affective Bias Modification Computer based sham Affective Bias Modification
Sham Affective bias modification: In the Affective bias modification (ABM) procedure, paired stimuli (e.g. a negative and a positive facial expression) are presented on a laptop screen, followed by one or two probes (dots) appearing in the spatial location of one of the stimuli. Participants are then required to press one of two buttons as quickly as possible to indicate the number of dots in the probe. Stimuli presentation time is 50% 500 ms and 50 % 1000 ms (evenly distributed throughout the task). In total, the ABM will comprise 90 trials of paired images of faces of different valences. In the sham condition, the probe appears at the location of the most positive stimuli of each pair in 50 % of trials (no contingency between facial expressions shown and the probe location). Participants will do ABM in their homes (approx. 5 min.) twice a day for two weeks (28 sessions) using laptop computers provided by us. | 45 |
| Assesment Only No intervention. | 5 |
| Total | 92 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 8 | 6 | 4 |
Baseline characteristics
| Characteristic | Active Affective Bias Modification | Sham Affective Bias Modification | Assesment Only | Total |
|---|---|---|---|---|
| Age, Continuous | 44.3 years STANDARD_DEVIATION 10.4 | 43.2 years STANDARD_DEVIATION 11.6 | 36.8 years STANDARD_DEVIATION 18.2 | 43.7 years STANDARD_DEVIATION 11 |
| Alcohol Use Disorder Identification Test (AUDIT) | 5.8 units on a scale STANDARD_DEVIATION 4.7 | 5.5 units on a scale STANDARD_DEVIATION 5.6 | 3.6 units on a scale STANDARD_DEVIATION 5.5 | 5.5 units on a scale STANDARD_DEVIATION 5.6 |
| Attentional bias | -10.7 milliseconds STANDARD_DEVIATION 26.4 | -4.7 milliseconds STANDARD_DEVIATION 36 | -17.1 milliseconds STANDARD_DEVIATION 29.3 | -8.1 milliseconds STANDARD_DEVIATION 15.9 |
| Beck's Anxiety Inventory (BAI) | 13.1 units on a scale STANDARD_DEVIATION 8.8 | 16.2 units on a scale STANDARD_DEVIATION 8.9 | 12.0 units on a scale STANDARD_DEVIATION 7.5 | 14.6 units on a scale STANDARD_DEVIATION 8.8 |
| Beck's Depression Inventory (BDI-II) | 23.1 units on a scale STANDARD_DEVIATION 10.6 | 26.3 units on a scale STANDARD_DEVIATION 9.8 | 18.2 units on a scale STANDARD_DEVIATION 3.8 | 24.4 units on a scale STANDARD_DEVIATION 9.9 |
| Brief State Rumination Inventory (BSRI) | 36.4 units on a scale STANDARD_DEVIATION 18.7 | 38.3 units on a scale STANDARD_DEVIATION 17.5 | 22.3 units on a scale STANDARD_DEVIATION 20.7 | 36.6 units on a scale STANDARD_DEVIATION 18.4 |
| Education level (ISCED) | 5.7 units on a scale STANDARD_DEVIATION 1.3 | 5.8 units on a scale STANDARD_DEVIATION 1.2 | 4.8 units on a scale STANDARD_DEVIATION 2.1 | 5.7 units on a scale STANDARD_DEVIATION 1.3 |
| Race and Ethnicity Not Collected | — | — | — | 0 Participants |
| Region of Enrollment Norway | 42 participants | 45 participants | 5 participants | 92 participants |
| Sex: Female, Male Female | 28 Participants | 36 Participants | 3 Participants | 67 Participants |
| Sex: Female, Male Male | 14 Participants | 9 Participants | 2 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 51 | 0 / 7 |
| other Total, other adverse events | 0 / 50 | 0 / 51 | 0 / 7 |
| serious Total, serious adverse events | 0 / 50 | 0 / 51 | 0 / 7 |
Outcome results
Primary
Self-reported Depressive Symptoms: Becks Depression Inventory-II
Self-reported depressive symptoms 6 months after the ABM intervention based on a 21-item scale. Each item is scored 0-3 (where scoring description is adapted to each item), yielding a score from 0-63.
Time frame: At 6 months follow-up
Population: Participants that had baseline and/or outcome data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Active Affective Bias Modification | Self-reported Depressive Symptoms: Becks Depression Inventory-II | 19.1 score on a scale | Standard Error 1.7 |
| Sham Affective Bias Modification | Self-reported Depressive Symptoms: Becks Depression Inventory-II | 16.5 score on a scale | Standard Error 1.6 |
| Assessment Only | Self-reported Depressive Symptoms: Becks Depression Inventory-II | 5.3 score on a scale | Standard Error 5.5 |
Comparison: We estimated a priori that a total of 100 participants would be needed to detect a difference between ABM and sham condition, with a two-tailed α of 0.05 and (1-β) of .80. Power calculation was based on the assumption that 50 % of the participants allocated to ABM would report a minimum of 3 points reduction on BDI-II at six months, compared to 20 % in the sham condition. Assuming 15 % lost to follow up, power calculation indicated the need for 50 participants in each conditionp-value: 0.05Mixed Models Analysis
Primary
State Rumination: Brief State Rumination Inventory
Self-reported state rumination after stress induction on a 8 item scale. Each item is scored on a 0-100 Visual Analogue Scale, yielding a score from 0-800, which is reported divided by 8 to provide a mean total item score. Hence the min= 0 and max = 100. A higher score indicates more state rumination.
Time frame: At two weeks follow up.
Population: 10 participants were lost to follow-up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Affective Bias Modification | State Rumination: Brief State Rumination Inventory | 34.2 score on a scale | Standard Deviation 15.8 |
| Sham Affective Bias Modification | State Rumination: Brief State Rumination Inventory | 32.3 score on a scale | Standard Deviation 15.8 |
| Assessment Only | State Rumination: Brief State Rumination Inventory | 23.4 score on a scale | Standard Deviation 20.2 |
Primary
State Rumination: Brief State Rumination Inventory (BSRI)
Change in self-reported state rumination after the stress induction from pre to post intervention on a 8 item scale. Difference score: BSRI post intervention - BRSI Baseline. A negative score means reduction in state rumination over the intervention. Each item is scored on a 0-100 Visual Analogue Scale. The total score divided by 8 to provide the mean item total score, hence the min= 0 and max = 100 for each of the BSRI assessment time points. It was hypothesized that change in state rumination over the intervention period would mediate the effect of ABM on depressive symptoms at six months follow up.
Time frame: At baseline and two weeks follow up.
Population: 10 persons were lost to follow up
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Affective Bias Modification | State Rumination: Brief State Rumination Inventory (BSRI) | -.7 score on a scale | Standard Deviation 13.3 |
| Sham Affective Bias Modification | State Rumination: Brief State Rumination Inventory (BSRI) | -5.8 score on a scale | Standard Deviation 19.1 |
| Assessment Only | State Rumination: Brief State Rumination Inventory (BSRI) | -.8 score on a scale | Standard Deviation 7.4 |
Secondary
Affective Bias: Dot-probe Task
Change in reaction time in milliseconds to probes in the location of the positive facial stimuli compared to probes in the location of the negative stimuli. Positive number implies reduction in negative bias.
Time frame: From baseline to two weeks follow up
Population: Nine participants were lost to follow up. Technical error led to loss of data on the follow up in the assessment only condition.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Affective Bias Modification | Affective Bias: Dot-probe Task | 18.0 milliseconds | Standard Deviation 28.4 |
| Sham Affective Bias Modification | Affective Bias: Dot-probe Task | 9.4 milliseconds | Standard Deviation 40.3 |
Secondary
Symptom Network Change: Experience Sampling of Depressive Symptoms
Changed centrality of rumination in networks estimated based on a 9-item experience sampling questionnaire of self-reported depressive symptoms scored on a 0-100 visual analogue scale (higher value, more symptoms; reversing interest, positive affect and activity; Kraft et al., 2023, Psychiatry Research Communications). Two person-specific networks (pre and post-intervention) were estimated using the var1-function in the R package psychonetrics, with full-information maximum likelihood estimator, based on the experience sampling questionnaires that were administrated 5 times/day for 14 days before and after the intervention. Centrality of rumination in these networks were calculated using qgraph (Epskamp et al., 2012) and standardized. Change in rumination centrality was calculated as difference between rumination centrality in the two estimated networks, and higher number indicate increased centrality of rumination (post-pre).
Time frame: From two weeks prior to baseline to two weeks after the two-week intervention.
Population: Pre-processing of ESM-data excluded participants who responded to less than 30 measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Affective Bias Modification | Symptom Network Change: Experience Sampling of Depressive Symptoms | .0175 standardized values | Standard Deviation 0.0819 |
| Sham Affective Bias Modification | Symptom Network Change: Experience Sampling of Depressive Symptoms | -.685 standardized values | Standard Deviation 0.789 |
Secondary
Symptom Network: Experience Sampling of Depressive Symptoms
Centrality of rumination in networks based on a 9-item experience sampling questionnaire of self-reported depressive symptoms scored on a 0-100 visual analogue scale (higher value, more symptoms; reversing interest, positive affect and activity; Kraft et al., 2023, Psychiatry Research Communications). Person-specific networks were estimated using the var1-function in the R package psychonetrics, with full-information maximum likelihood estimator, based on the experience sampling questionnaires that were administrated 5 times/day for 14 days after the two-week intervention. Centrality of rumination in this network was calculated using qgraph (Epskamp et al., 2012) and standardized. Higher number indicate higher centrality of rumination.
Time frame: Two weeks after the two-week intervention.
Population: Participants who responded to 30 measurements or more.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Affective Bias Modification | Symptom Network: Experience Sampling of Depressive Symptoms | .108 standardized values | Standard Deviation 0.785 |
| Sham Affective Bias Modification | Symptom Network: Experience Sampling of Depressive Symptoms | -.230 standardized values | Standard Deviation 0.824 |