Major DepressionNCT02931487
Restoring Emotion Regulation Networks in Depression Vulnerability
A study testing Attentional Bias Modification in people with Major Depression, run by University of Oslo at 1 site in Norway.
Trial summary
Selective biases in attention can be modified by a simple computerized technique: The Attention Bias Modification Task (ABM) pioneered by MacLeod et al. Cognitive biases may be one reason depression recurs, and altering these biases should reduce risk of recurrence. Recently, evidence has supported this hypothesis . Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Major Depression
- What is being tested?
- Attentional Bias Modification
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 134 participants
- Where
- 1 siteNorway
- Study dates
- May 2015to Dec 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Currently no-depressed subjects with a history of major depression.
Who cannot join
- Current or past neurological illness, bipolar disorder, psychosis or drug addiction.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Restoring Emotion Regulation Networks in Depression Vulnerability: An Experimental Study Applying an Attention Bias Modification Procedure
Selective biases in attention can be modified by a simple computerized technique: The Attention Bias Modification Task (ABM) pioneered by MacLeod et al. Cognitive biases may be one reason depression recurs, and altering these biases should reduce risk of recurrence. Recently, evidence has supported this hypothesis . The mechanisms by which ABM works are not well understood. More research is needed to explore how altering an implicit attentional bias can lead to changes in subjective mood. One possible explanation is that positive attentional biases are an important component of explicit methods of emotion regulation. The ability to effectively regulate one's emotions is a fundamental component of mental health and this ability is impaired in depression. It has also been shown that recovered depressed people spontaneously show a more dysfunctional pattern of emotion regulation as compared to never depressed controls. Supporting this, growing evidence implicates dysregulation of a medial/orbitofrontal circuit in mood disorders. This circuit includes the orbitofrontal cortex and anterior cingulate cortex, the ventral striatum, the ventral pallidum and medial thalamus. Components of this circuit are reciprocally connected with the amygdala, which is implicated in emotional processing in the healthy brain and dysregulated in depression. Negative emotion processing biases depend on both enhanced "bottom-up" responses to emotionally salient stimuli and reduces "top-down" cognitive control mechanisms, required to suppress responses to emotionally salient but task irrelevant information. Cognitive reappraisal and distancing are common strategies to down- or upregulate emotional responses. Reappraisal is an emotion regulation strategy that involves reinterpretation and changing the way one thinks about an event or stimulus with the goal of changing its affective impact. Distancing is a type of reappraisal that involves creating mental space between oneself and the emotional event in order to see things from a different, less self-focused perspective. It has been shown that distancing is a strategy that people can improve at over time compared to reinterpretation. The neural systems which support the explicit regulation of emotion have previously been characterized and include both lateral- and prefrontal cortex. This frontal activity is predicted to downregulate limbic circuitry involving the amygdala during passive viewing of emotional salient stimuli.
- Conditions
- Major Depression
- Being tested
- Attentional Bias Modification, Sham Comparator
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Attentional Bias ModificationBehavioural
Computerized
Sham ComparatorBehavioural
Computerized
| Study group | Role | What they receive |
|---|---|---|
| Attentional Bias Modification | Experimental | ABM dot-probe task with image stimuli (faces) of three valences: positive (happy), neutral, or negative (angry and fearful). In the ABM condition, probes were located behind positive stimuli in 87 % of the trials (valid trials), as opposed to 13% with probes located behind the more negative stimuli (invalid trials). Consequently, participants should implicitly learn to deploy their attention toward positive stimuli, and in this way develop a more positive AB when completing the task. Receives: Behavioral: Attentional Bias Modification |
| Sham comparator | Sham comparator | Sham condition without modification of attentional bias. These trials are identical in structure to the ABM trials with the exception that target probes replaced negative and positive images with equal frequency. Receives: Behavioral: Sham Comparator |
What is being measured
The primary outcome is the main question the study is designed to answer.
BOLD response in prefrontal cortical regions
Stronger fMRI BOLD response in prefrontal cortical regions in ABMT compared to neutral AMB placebo condition.
Measured: Two weeks after after ABM-training
Secondary outcomes (8)
BOLD response within the amygdala
Lower ABM fMRI BOLD response within the amygdala in ABMT compared to neutral ABM placebo condition.
Measured: Two weeks after ABM-training
DTI
Increased neural integrity as measured by fractional anisotropy values in the uncinate fasciculi (UF) in the active AMBT compared to neutral ABM placebo condition.
Measured: Two weeks after ABM-training
RSFC
Increased integrity within the attentional networks at rest as measured by independent component analysis (ICA) in ABMT compared to neutral ABM training.
Measured: Two weeks after ABM-training
5-HTTLPR + A>G polymorphic variation divided by the triallelic functional "high expressive" versus "low expressive" genotype will moderate the impact from ABMT as measured by whole brain BOLD responses.
The low expressive variant will be associated with more frontal BOLD activation and lower amygdala activation after ABMT
Measured: Two weeks after ABM-training
BDNF
Brain Derived Neurotropic Factor (BDNF) val66met polymorphic variation linked to Brain Derived Neurotropic Factor (BDNF) variation will differentiate between ABMT and neutral AMB placebo as measured by fMRI whole brain BOLD responses.
Measured: Two week after ABM-training
Serotonergic cumulative genetic score and fMRI
A serotonergic cumulative Genetic score, including (5-HHTLPR, HTR1A 8rs6295) and HTR 2A (rs 6311) polymorphisms will moderate the effects of ABM on fMRI BOLD signal compared to a neutral placebo condition.
Measured: Two weeks after ABM-training
Serotonergic cumulative genetic score and morphompetry
A serotonergic cumulative Genetic score, including (5-HHTLPR, HTR1A 8rs6295) and HTR 2A (rs 6311) polymorphisms will moderate the effects of ABM on structural MRI as measured by total grey matter volume compared to a neutral placebo condition.
Measured: Two weeks after ABM-training
Serotonergic cumulative genetic score and fMRI and DTI
A serotonergic cumulative Genetic score, including (5-HHTLPR, HTR1A 8rs6295) and HTR 2A (rs 6311) polymorphisms will moderate the effects of ABM on DTI MRI as measured by fractional anisotropy compared to a neutral placebo condition.
Measured: Two weeks after ABM-training
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2016 (estimated)
- Study startMay 2015
- Primary completionDec 2016
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Major DepressionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 134 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oslo
- Sponsor type
- University, hospital or other
- Collaborators
- Oslo University Hospital, University of Oxford
- Responsible party
- Principal investigator, Nils Inge Landrø, University of Oslo
- Investigators
- Nils I Landrø, phd, Principal investigator, University of Oslo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02931487
- Sponsor's protocol ID
- HSØ-2015052
- Status last verified
- Apr 2019
- First submitted
- 8 Jul 2016
- Last updated
- 30 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Hilland E, Landro NI ;, Harmer CJ, Browning M, Maglanoc LA, Jonassen R. Attentional bias modification is associated with fMRI response toward negative stimuli in individuals with residual depression: a randomized controlled trial. J Psychiatry Neurosci. 2020 Jan 1;45(1):23-33. doi: 10.1503/jpn.180118.
PubMed 31397551Hilland E, Landro NI, Harmer CJ, Maglanoc LA, Jonassen R. Within-Network Connectivity in the Salience Network After Attention Bias Modification Training in Residual Depression: Report From a Preregistered Clinical Trial. Front Hum Neurosci. 2018 Dec 21;12:508. doi: 10.3389/fnhum.2018.00508. eCollection 2018.
PubMed 30622463
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Restoring Emotion Regulation Networks in Depression Vulnerability: An Experimental Study Applying an Attention Bias Modification Procedure
- ClinicalTrials.gov ID
- NCT02931487
- Acronym / sponsor ID
- HSØ-2015052
- Conditions
- Major Depression
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 134 participants (actual)
- Lead sponsor
- University of OsloUniversity, hospital or other
- Collaborators
- Oslo University Hospital, University of Oxford
- Study start
- May 2015
- Primary completion
- Dec 2016 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 13 Oct 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Selective biases in attention can be modified by a simple computerized technique: The Attention Bias Modification Task (ABM) pioneered by MacLeod et al. Cognitive biases may be one reason depression recurs, and altering these biases should reduce risk of recurrence. Recently, evidence has supported this hypothesis . The mechanisms by which ABM works are not well understood. More research is needed to explore how altering an implicit attentional bias can lead to changes in subjective mood. One possible explanation is that positive attentional biases are an important component of explicit methods of emotion regulation. The ability to effectively regulate one's emotions is a fundamental component of mental health and this ability is impaired in depression. It has also been shown that recovered depressed people spontaneously show a more dysfunctional pattern of emotion regulation as compared to never depressed controls. Supporting this, growing evidence implicates dysregulation of a medial/orbitofrontal circuit in mood disorders. This circuit includes the orbitofrontal cortex and anterior cingulate cortex, the ventral striatum, the ventral pallidum and medial thalamus. Components of this circuit are reciprocally connected with the amygdala, which is implicated in emotional processing in the healthy brain and dysregulated in depression. Negative emotion processing biases depend on both enhanced "bottom-up" responses to emotionally salient stimuli and reduces "top-down" cognitive control mechanisms, required to suppress responses to emotionally salient but task irrelevant information. Cognitive reappraisal and distancing are common strategies to down- or upregulate emotional responses. Reappraisal is an emotion regulation strategy that involves reinterpretation and changing the way one thinks about an event or stimulus with the goal of changing its affective impact. Distancing is a type of reappraisal that involves creating mental space between oneself and the emotional event in order to see things from a different, less self-focused perspective. It has been shown that distancing is a strategy that people can improve at over time compared to reinterpretation. The neural systems which support the explicit regulation of emotion have previously been characterized and include both lateral- and prefrontal cortex. This frontal activity is predicted to downregulate limbic circuitry involving the amygdala during passive viewing of emotional salient stimuli.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Attentional Bias Modification | Experimental | Behavioral: Attentional Bias ModificationABM dot-probe task with image stimuli (faces) of three valences: positive (happy), neutral, or negative (angry and fearful). In the ABM condition, probes were located behind positive stimuli in 87 % of the trials (valid trials), as opposed to 13% with probes located behind the more negative stimuli (invalid trials). Consequently, participants should implicitly learn to deploy their attention toward positive stimuli, and in this way develop a more positive AB when completing the task. |
| Sham comparator | Sham comparator | Behavioral: Sham ComparatorSham condition without modification of attentional bias. These trials are identical in structure to the ABM trials with the exception that target probes replaced negative and positive images with equal frequency. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Currently no-depressed subjects with a history of major depression.
Key exclusion criteria (1 listed)
- Current or past neurological illness, bipolar disorder, psychosis or drug addiction.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Attentional Bias ModificationComputerized | Behavioural | Attentional Bias Modification |
| Sham ComparatorComputerized | Behavioural | Sham comparator |
Primary outcome
BOLD response in prefrontal cortical regions
Time frame: Two weeks after after ABM-training
Stronger fMRI BOLD response in prefrontal cortical regions in ABMT compared to neutral AMB placebo condition.
8 secondary outcomes
BOLD response within the amygdala
Time frame: Two weeks after ABM-training
DTI
Time frame: Two weeks after ABM-training
RSFC
Time frame: Two weeks after ABM-training
5-HTTLPR + A>G polymorphic variation divided by the triallelic functional "high expressive" versus "low expressive" genotype will moderate the impact from ABMT as measured by whole brain BOLD responses.
Time frame: Two weeks after ABM-training
BDNF
Time frame: Two week after ABM-training
Serotonergic cumulative genetic score and fMRI
Time frame: Two weeks after ABM-training
Serotonergic cumulative genetic score and morphompetry
Time frame: Two weeks after ABM-training
Serotonergic cumulative genetic score and fMRI and DTI
Time frame: Two weeks after ABM-training
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2019.
- Derived from this study: PubMed 31397551Hilland E, Landro NI ;, Harmer CJ, Browning M, Maglanoc LA, Jonassen R. Attentional bias modification is associated with fMRI response toward negative stimuli in individuals with residual depression: a randomized controlled trial. J Psychiatry Neurosci. 2020 Jan 1;45(1):23-33. doi: 10.1503/jpn.180118.
- Derived from this study: PubMed 30622463Hilland E, Landro NI, Harmer CJ, Maglanoc LA, Jonassen R. Within-Network Connectivity in the Salience Network After Attention Bias Modification Training in Residual Depression: Report From a Preregistered Clinical Trial. Front Hum Neurosci. 2018 Dec 21;12:508. doi: 10.3389/fnhum.2018.00508. eCollection 2018.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nils I Landrø, phd principal investigator
University of Oslo
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Attentional Bias Modification in people with Major Depression, run by University of Oslo at 1 site in Norway.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
BOLD response in prefrontal cortical regions (time frame: Two weeks after after ABM-training). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02931487, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Apr 2019.