Major Depressive DisorderNCT00075296
FMRI Study of Performance During a Probabilistic Reversal Learning Task in Depression
An observational study of Major Depressive Disorder, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial summary
This study will examine how the brains of depressed people function during learning and respond to feedback. Participants perform a "probabilistic reversal learning task" to determine whether depressed people perform worse on a task than non-depressed people when they sometimes receive misleading negative feedback. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Major Depressive Disorder
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Jan 2004to 21 Apr 2008
- Phase
- Observational
- 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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- All subjects will be between 18 and 50 years old. Male and female subjects will be included. All subjects must be able to give written informed consent prior to participation in this study.
- MDD Depressed Sample: Twenty five subjects (ages 18-50) male and female will be selected, with primary MDD currently depressed as defined by DSM-IV criteria for recurrent MDD, in a current major depressive episode and who have a first degree relative with MDD but no first degree relatives with mania, alcoholism, or antisocial personality disorder.
- MDD Remission Sample: Twenty subjects (ages 18-50) male and female will be selected. Remission is defined as a period of at least three months during which the subject has not taken an antidepressant agent, with Hamilton Depression Rating Scale (HDRS; 21-item; Hamilton 1960) scores in the non-depressed range (less than 8), and with no more than one clinically significant depressive symptom.
- Bipolar Depressed Sample: Twenty five subjects (ages 18-50) male and female will be selected who meet DSM-IV criteria for bipolar I or II disorder and are currently in a depressed phase.
- Healthy Control Sample: Thirty subjects (ages 18-50) male and female who have not met criteria for any major psychiatric disorder will be selected. From this large sample a control subject will be matched to each depressed subject for age, gender, handedness and IQ. The control subjects will have no known first degree relatives with mood disorders.
Who cannot join
- Individuals with any major medical or neurological disorder or who have received psychotropic drugs or medication likely to influence cerebral blood flow or metabolism within 3 weeks (8 weeks for fluoxetine [Prozac]), of scanning.
- Bipolar subjects with rapid cycling or with current psychosis will be excluded from the protocol.
- Effective treatment will not be discontinued for the purposes of this protocol, subjects will be identified who have never been treated or who have discontinued medication due to lack of efficacy, noncompliance, physician order or other reasons prior to study entry.
- Individuals who meet DSM-IV criteria for alcohol and/or substance abuse within 1 year prior to screening or lifetime history of substance dependence.
- Women of childbearing potential who are known to be pregnant or who have a positive pregnancy test.
- Individuals who have experienced serious suicidal ideation within the past 2 months.
- General exclusions for MRI imaging, such as having had a cardiac pacemaker or ferromagnetic object implanted through surgical intervention or accident (for example: shrapnel).
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
This study will examine how the brains of depressed people function during learning and respond to feedback. Participants perform a "probabilistic reversal learning task" to determine whether depressed people perform worse on a task than non-depressed people when they sometimes receive misleading negative feedback.
Right-handed healthy volunteers, people with major depression who are currently depressed or have previously been depressed and people with bipolar depression between 18 and 50 years of age may be eligible for this study. Candidates are screened with a medical and psychiatric history, physical examination, electrocardiogram, blood and urine tests. They are also interviewed to evaluate mood, sleep, energy, work and school performance, and social relationships, and asked to answer questions to investigate whether any history of paranoia, panic attacks, obsession, compulsions, suicidal thoughts, eating disturbances, and alcohol or drug abuse is present. They complete rating scales for depression, anxiety, and negative thinking; history of alcohol and tobacco use; physical movement; socioeconomic status; overall level of functioning; and depression type. Finally, they undergo a battery of neuropsychological tests to assess general intelligence, handedness, and specific cognitive abilities, including memory and concentration.
Read more
Participants perform the probabilistic reversal learning task either in a testing room seated in front of a computer or lying down while undergoing functional magnetic resonance imaging (FMRI). FMRI is a diagnostic test that uses a strong magnet and radio waves to obtain pictures of brain structure and function. For the scan, the subject lies on a narrow bed with a plastic-encased metal coil close to the head. The bed slides into the scanner - a small tunnel about 6 feet long. All subjects, whether in the testing room or in the MRI scanner, undergo the learning task as follows:
Two patterns are presented on a computer screen. One pattern is designated "correct" and the other "incorrect." Subjects are asked to choose the correct pattern on each try and are provided feedback as to whether the response was right or wrong. Sometimes the rule changes, and the pattern that was correct is now wrong, and vice versa, so that the new correct pattern must be chosen. In addition, misleading feedback is sometimes given intentionally, indicating the subject chose the wrong pattern when in fact the response was correct. Subjects should change their response only when they are sure that the rule has changed, and not because they were incorrectly told that they were wrong. For patients undergoing MRI, blood flow in the different areas of the brain is measured during the test.
After the test, outside the scanner, participants undergo additional tests of attention, memory, and concentration like those that were administered during the screening procedures.
Read the detailed description
When depressed subjects perceive they have failed while performing a neuropsychological task their performance on subsequent trials becomes impaired. Elliott et al. showed that MDD subjects were far more likely to fail on subsequent tasks after failure on one task than controls. This effect has been described as an "abnormal response' to negative feedback or a 'catastrophic response to perceived failure.'
Murphy et al. investigated this further using a probabilistic reversal learning task in which subjects were faced with occasional negative feedback that was actually false. On each trial of the task subjects choose one of two stimuli on screen, one considered correct and the other incorrect, this is followed by feedback. Instructions prior to starting the task inform the subject that sometimes the rule will change and the previously correct stimulus will be incorrect, but sometimes the computer will give them incorrect feedback. They are instructed to switch responding only when they are sure the rule has actually changed. MDD subjects demonstrate intact acquisition and reversal of probabilistic learning but are impaired in their ability to maintain a response in the face of misleading negative feedback. This profile of impairment may be relatively specific to MDD as, for example, it is not found in subjects with other neuropsychiatric conditions. This 'abnormal response' to negative feedback may represent a significant link between negative affect and cognitive impairments in depression.
During the proposed study functional magnetic resonance images will be acquired while subjects perform a version of the probabilistic reversal learning task. Four groups will take part: MDD, bipolar depressed, unmedicated MDD in remission and healthy control subjects. These images will be used to investigate differences in neural activation between the four groups, to clarify whether this specific profile of behavioral response extends to bipolar depressed subjects and to assess the mood state dependences of this effect. This would increase understanding of the specific profile of performance on this task and neural basis of this abnormal response to negative feedback that contributes to impairment of cognitive performance in depression.
- Conditions
- Major Depressive Disorder
- Keywords
- Major Depressive Disorder, Bipolar Disorder, Negative Feedback, Cognitive Performance, Negative Affect, Depression, Major Depression, MDD, Healthy Volunteer, HV
- Medical subject headings
- Depressive Disorder, Major, Bipolar Disorder, Depression
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2004 (estimated)
- Study start5 Jan 2004
- Study completion21 Apr 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies 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
- Observational
- Enrolment
- 100 participants
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00075296
- Sponsor's protocol ID
- 040075
- Other IDs
- 04-M-0075
- Status last verified
- 21 Apr 2008
- First submitted
- 8 Jan 2004
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
BECK AT, WARD CH, MENDELSON M, MOCK J, ERBAUGH J. An inventory for measuring depression. Arch Gen Psychiatry. 1961 Jun;4:561-71. doi: 10.1001/archpsyc.1961.01710120031004. No abstract available.
PubMed 13688369
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- FMRI Study of Performance During a Probabilistic Reversal Learning Task in Depression
- ClinicalTrials.gov ID
- NCT00075296
- Acronym / sponsor ID
- 040075
- Conditions
- Major Depressive Disorder
- Keywords
- Major Depressive Disorder, Bipolar Disorder, Negative Feedback, Cognitive Performance, Negative Affect, Depression, Major Depression, MDD
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 100 participants
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- 5 Jan 2004
- Study completion
- 21 Apr 2008
- First posted
- 9 Jan 2004 (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.
This study will examine how the brains of depressed people function during learning and respond to feedback. Participants perform a "probabilistic reversal learning task" to determine whether depressed people perform worse on a task than non-depressed people when they sometimes receive misleading negative feedback.
Right-handed healthy volunteers, people with major depression who are currently depressed or have previously been depressed and people with bipolar depression between 18 and 50 years of age may be eligible for this study. Candidates are screened with a medical and psychiatric history, physical examination, electrocardiogram, blood and urine tests. They are also interviewed to evaluate mood, sleep, energy, work and school performance, and social relationships, and asked to answer questions to investigate whether any history of paranoia, panic attacks, obsession, compulsions, suicidal thoughts, eating disturbances, and alcohol or drug abuse is present. They complete rating scales for depression, anxiety, and negative thinking; history of alcohol and tobacco use; physical movement; socioeconomic status; overall level of functioning; and depression type. Finally, they undergo a battery of neuropsychological tests to assess general intelligence, handedness, and specific cognitive abilities, including memory and concentration.
Participants perform the probabilistic reversal learning task either in a testing room seated in front of a computer or lying down while undergoing functional magnetic resonance imaging (FMRI). FMRI is a diagnostic test that uses a strong magnet and radio waves to obtain pictures of brain structure and function. For the scan, the subject lies on a narrow bed with a plastic-encased metal coil close to the head. The bed slides into the scanner - a small tunnel about 6 feet long. All subjects, whether in the testing room or in the MRI scanner, undergo the learning task as follows:
Two patterns are presented on a computer screen. One pattern is designated "correct" and the other "incorrect." Subjects are asked to choose the correct pattern on each try and are provided feedback as to whether the response was right or wrong. Sometimes the rule changes, and the pattern that was correct is now wrong, and vice versa, so that the new correct pattern must be chosen. In addition, misleading feedback is sometimes given intentionally, indicating the subject chose the wrong pattern when in fact the response was correct. Subjects should change their response only when they are sure that the rule has changed, and not because they were incorrectly told that they were wrong. For patients undergoing MRI, blood flow in the different areas of the brain is measured during the test.
After the test, outside the scanner, participants undergo additional tests of attention, memory, and concentration like those that were administered during the screening procedures.
Detailed description
When depressed subjects perceive they have failed while performing a neuropsychological task their performance on subsequent trials becomes impaired. Elliott et al. showed that MDD subjects were far more likely to fail on subsequent tasks after failure on one task than controls. This effect has been described as an "abnormal response' to negative feedback or a 'catastrophic response to perceived failure.'
Murphy et al. investigated this further using a probabilistic reversal learning task in which subjects were faced with occasional negative feedback that was actually false. On each trial of the task subjects choose one of two stimuli on screen, one considered correct and the other incorrect, this is followed by feedback. Instructions prior to starting the task inform the subject that sometimes the rule will change and the previously correct stimulus will be incorrect, but sometimes the computer will give them incorrect feedback. They are instructed to switch responding only when they are sure the rule has actually changed. MDD subjects demonstrate intact acquisition and reversal of probabilistic learning but are impaired in their ability to maintain a response in the face of misleading negative feedback. This profile of impairment may be relatively specific to MDD as, for example, it is not found in subjects with other neuropsychiatric conditions. This 'abnormal response' to negative feedback may represent a significant link between negative affect and cognitive impairments in depression.
During the proposed study functional magnetic resonance images will be acquired while subjects perform a version of the probabilistic reversal learning task. Four groups will take part: MDD, bipolar depressed, unmedicated MDD in remission and healthy control subjects. These images will be used to investigate differences in neural activation between the four groups, to clarify whether this specific profile of behavioral response extends to bipolar depressed subjects and to assess the mood state dependences of this effect. This would increase understanding of the specific profile of performance on this task and neural basis of this abnormal response to negative feedback that contributes to impairment of cognitive performance in depression.
Study design
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- All subjects will be between 18 and 50 years old. Male and female subjects will be included. All subjects must be able to give written informed consent prior to participation in this study.
- MDD Depressed Sample: Twenty five subjects (ages 18-50) male and female will be selected, with primary MDD currently depressed as defined by DSM-IV criteria for recurrent MDD, in a current major depressive episode and who have a first degree relative with MDD but no first degree relatives with mania, alcoholism, or antisocial personality disorder.
- MDD Remission Sample: Twenty subjects (ages 18-50) male and female will be selected. Remission is defined as a period of at least three months during which the subject has not taken an antidepressant agent, with Hamilton Depression Rating Scale (HDRS; 21-item; Hamilton 1960) scores in the non-depressed range (less than 8), and with no more than one clinically significant depressive symptom.
- Bipolar Depressed Sample: Twenty five subjects (ages 18-50) male and female will be selected who meet DSM-IV criteria for bipolar I or II disorder and are currently in a depressed phase.
- Healthy Control Sample: Thirty subjects (ages 18-50) male and female who have not met criteria for any major psychiatric disorder will be selected. From this large sample a control subject will be matched to each depressed subject for age, gender, handedness and IQ. The control subjects will have no known first degree relatives with mood disorders.
Key exclusion criteria (7 listed)
- Individuals with any major medical or neurological disorder or who have received psychotropic drugs or medication likely to influence cerebral blood flow or metabolism within 3 weeks (8 weeks for fluoxetine [Prozac]), of scanning.
- Bipolar subjects with rapid cycling or with current psychosis will be excluded from the protocol.
- Effective treatment will not be discontinued for the purposes of this protocol, subjects will be identified who have never been treated or who have discontinued medication due to lack of efficacy, noncompliance, physician order or other reasons prior to study entry.
- Individuals who meet DSM-IV criteria for alcohol and/or substance abuse within 1 year prior to screening or lifetime history of substance dependence.
- Women of childbearing potential who are known to be pregnant or who have a positive pregnancy test.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
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 2 Jul 2017.
- Background: PubMed 13688369BECK AT, WARD CH, MENDELSON M, MOCK J, ERBAUGH J. An inventory for measuring depression. Arch Gen Psychiatry. 1961 Jun;4:561-71. doi: 10.1001/archpsyc.1961.01710120031004. No abstract available.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Major Depressive Disorder, run by National Institute of Mental Health (NIMH) at 1 site in United States.
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 5 inclusion and 7 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 2 Jul 2017. 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 United States. 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. 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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00075296, which also lists 1 linked publication.
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 2 Jul 2017.