DepressionNCT00749125
fMRI Studies of Emotional Brain Circuitry in People With Major Depression
A study testing Lexapro in people with Depression, run by Washington University School of Medicine.
Trial summary
This study will examine activation of a brain circuit that regulates emotion in depressed patients before and after treatment to see which areas of the brain are involved in chronic depression. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Depression
- What is being tested?
- Lexapro
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 99 participants
- Where
- No sites listed yet
- Study dates
- Jul 2001to Jun 2008
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Participant meets DSM-IV criteria for major depressive disorder
- Minimum score greater than 18 on Hamilton Depression Inventory
- Participant is right handed
- Participant speaks English
Who cannot join
- Significant limitations that would interfere with testing procedures, such as uncorrected visual or hearing loss
- MRI contraindications, such as foreign metallic implants or a pacemaker
- Known primary neurological disorders, including dementia, stroke, encephalopathy, Parkinson's disease, brain tumors, multiple sclerosis, or seizure disorder
- Severe or unstable medical illness, such as a heart attack within the past 3 months, end stage cancer, or conditions or drugs that may cause depression (like systemic steroids or uncorrected hypothyroidism)
- Currently at risk for suicide
- Known allergy or hypersensitivity to escitalopram
About this study
Official title: fMRI Studies of Emotional Circuitry in Major Depression
This study will examine activation of a brain circuit that regulates emotion in depressed patients before and after treatment to see which areas of the brain are involved in chronic depression.
Read the detailed description
Major depressive disorder can be a recurrent problem for many people, interfering with their ability to function normally in day-to-day life. Although research shows that activation in certain brain areas corresponds to certain emotional functions, it is not well known which specific changes in brain functioning are related to or caused by depression. A proposed theory holds that depression is related to abnormal regulation of emotions and thoughts. This study will focus particularly on a brain circuit involved in emotional regulation, which includes the amygdala, the affective division of the anterior cingulate (ACad), and dorsolateral prefrontal cortex (DLPFC). The amygdala detects critical emotional information, especially threats; the ACad judges relevance of motivational cues, detects conflict, and regulates emotional responses; and the DLPFC has a critical role in supporting a wide range of cognitive control functions. This study will compare brain scans from people with and without depression to attempt to clarify which changes in brain functioning are related to depression.
Participation in this study will last 8 weeks. All participants will undergo initial screening in a telephone interview, then a diagnostic interview and brief physical examination. After passing through screening, participants will schedule a functional magnetic resonance imaging (fMRI) scan. The fMRI scan, lasting approximately 2 hours, will take pictures of both brain structure and brain functioning during different tasks. Also at this visit but outside the fMRI scanner, participants will be asked to complete an additional 2 hours of tasks on a computer. Depressed participants will then be given Lexapro, an approved drug for the treatment of depression. Participants taking Lexapro will go to scheduled doctor's visits after 2, 4, and 6 weeks of treatment to assess health, effectiveness of the drug, and side effects. On the eighth week, all participants will again undergo fMRI scanning and computer testing. At both the initial and follow-up fMRI study visits, images of brain function and anatomy will be recorded, heart rate will be monitored, and anxiety and arousal will be measured in the computer tests.
- Conditions
- Depression
- Being tested
- Lexapro
- Keywords
- Emotional Circuitry, fMRI
- Medical subject headings
- Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LexaproDrug
Also called Escitalopram
10 mg by mouth once per day for first 2 weeks, with psychiatric re-evaluation every 2 weeks to determine if any change in dosage is required, with a maximum of 20 mg per day
| Study group | Role | What they receive |
|---|---|---|
| 1 Lexapro | Experimental | The depressed participants in this arm will be given Lexapro. Receives: Drug: Lexapro |
| 2 Control | No intervention | The nondepressed participants in this arm will not be given any intervention for depression. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Activations in Different Cortical Regions Caused by Emotionally Evocative Task
MRI scans from 41 participants (23 depressed and 18 controls), including fMRI scans using an emotional distractor task, were analyzed for differences between groups in activation in a priori regions (amygdala and DLPFC), measured with BOLD signal, for two conditions of the task - attend fearful and ignore fearful, both at baseline and following 8 weeks of treatment for the depressed group. Voxel-wise comparisons (ANOVAs) were performed to determine differences in activations between groups within these regions. Positive values reflect a BOLD activation in that region; negative reflects a BOLD de-activation in that region. We expect more positive values (greater activation) in depressed participants at baseline than in controls during the attend fearful task, and more negative values (greater de-activation) in controls at baseline than depressed during the ignore fearful task. These differences were expected to lessen significantly following treatment in the depressed group.
Measured: baseline and week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2008 (estimated)
- Study startJul 2001
- Primary completionJan 2008
- Study completionJun 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for DepressionStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- 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
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 99 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
- Investigators
- Yvette I. Sheline, MD, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00749125
- Sponsor's protocol ID
- R01MH064821-04
- Other IDs
- R01MH064821, 5R01 MH06482104, DATR A3-NSM
- Status last verified
- Jun 2018
- First submitted
- 8 Sep 2008
- Last updated
- 17 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Sheline YI. Neuroimaging studies of mood disorder effects on the brain. Biol Psychiatry. 2003 Aug 1;54(3):338-52. doi: 10.1016/s0006-3223(03)00347-0.
PubMed 12893109Fales CL, Barch DM, Rundle MM, Mintun MA, Mathews J, Snyder AZ, Sheline YI. Antidepressant treatment normalizes hypoactivity in dorsolateral prefrontal cortex during emotional interference processing in major depression. J Affect Disord. 2009 Jan;112(1-3):206-11. doi: 10.1016/j.jad.2008.04.027. Epub 2008 Jun 17.
PubMed 18559283Sheline YI, Price JL, Yan Z, Mintun MA. Resting-state functional MRI in depression unmasks increased connectivity between networks via the dorsal nexus. Proc Natl Acad Sci U S A. 2010 Jun 15;107(24):11020-5. doi: 10.1073/pnas.1000446107. Epub 2010 Jun 1.
PubMed 20534464Sheline YI, Barch DM, Donnelly JM, Ollinger JM, Snyder AZ, Mintun MA. Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment: an fMRI study. Biol Psychiatry. 2001 Nov 1;50(9):651-8. doi: 10.1016/s0006-3223(01)01263-x.
PubMed 11704071Fales CL, Barch DM, Rundle MM, Mintun MA, Snyder AZ, Cohen JD, Mathews J, Sheline YI. Altered emotional interference processing in affective and cognitive-control brain circuitry in major depression. Biol Psychiatry. 2008 Feb 15;63(4):377-84. doi: 10.1016/j.biopsych.2007.06.012. Epub 2007 Aug 24.
PubMed 17719567Sheline YI, Barch DM, Price JL, Rundle MM, Vaishnavi SN, Snyder AZ, Mintun MA, Wang S, Coalson RS, Raichle ME. The default mode network and self-referential processes in depression. Proc Natl Acad Sci U S A. 2009 Feb 10;106(6):1942-7. doi: 10.1073/pnas.0812686106. Epub 2009 Jan 26.
PubMed 19171889
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- fMRI Studies of Emotional Circuitry in Major Depression
- ClinicalTrials.gov ID
- NCT00749125
- Acronym / sponsor ID
- R01MH064821-04
- Conditions
- Depression
- Keywords
- Emotional Circuitry, fMRI
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 99 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Jul 2001
- Primary completion
- Jan 2008 (actual)
- Study completion
- Jun 2008 (actual)
- First posted
- 9 Sep 2008 (estimated)
- Results
- Posted 17 Jul 2018
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 activation of a brain circuit that regulates emotion in depressed patients before and after treatment to see which areas of the brain are involved in chronic depression.
Detailed description
Major depressive disorder can be a recurrent problem for many people, interfering with their ability to function normally in day-to-day life. Although research shows that activation in certain brain areas corresponds to certain emotional functions, it is not well known which specific changes in brain functioning are related to or caused by depression. A proposed theory holds that depression is related to abnormal regulation of emotions and thoughts. This study will focus particularly on a brain circuit involved in emotional regulation, which includes the amygdala, the affective division of the anterior cingulate (ACad), and dorsolateral prefrontal cortex (DLPFC). The amygdala detects critical emotional information, especially threats; the ACad judges relevance of motivational cues, detects conflict, and regulates emotional responses; and the DLPFC has a critical role in supporting a wide range of cognitive control functions. This study will compare brain scans from people with and without depression to attempt to clarify which changes in brain functioning are related to depression.
Participation in this study will last 8 weeks. All participants will undergo initial screening in a telephone interview, then a diagnostic interview and brief physical examination. After passing through screening, participants will schedule a functional magnetic resonance imaging (fMRI) scan. The fMRI scan, lasting approximately 2 hours, will take pictures of both brain structure and brain functioning during different tasks. Also at this visit but outside the fMRI scanner, participants will be asked to complete an additional 2 hours of tasks on a computer. Depressed participants will then be given Lexapro, an approved drug for the treatment of depression. Participants taking Lexapro will go to scheduled doctor's visits after 2, 4, and 6 weeks of treatment to assess health, effectiveness of the drug, and side effects. On the eighth week, all participants will again undergo fMRI scanning and computer testing. At both the initial and follow-up fMRI study visits, images of brain function and anatomy will be recorded, heart rate will be monitored, and anxiety and arousal will be measured in the computer tests.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 Lexapro | Experimental | Drug: LexaproThe depressed participants in this arm will be given Lexapro. |
| 2 Control | No intervention | –The nondepressed participants in this arm will not be given any intervention for depression. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Participant meets DSM-IV criteria for major depressive disorder
- Minimum score greater than 18 on Hamilton Depression Inventory
- Participant is right handed
- Participant speaks English
Key exclusion criteria (6 listed)
- Significant limitations that would interfere with testing procedures, such as uncorrected visual or hearing loss
- MRI contraindications, such as foreign metallic implants or a pacemaker
- Known primary neurological disorders, including dementia, stroke, encephalopathy, Parkinson's disease, brain tumors, multiple sclerosis, or seizure disorder
- Severe or unstable medical illness, such as a heart attack within the past 3 months, end stage cancer, or conditions or drugs that may cause depression (like systemic steroids or uncorrected hypothyroidism)
- Currently at risk for suicide
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 |
|---|---|---|
| LexaproAlso: Escitalopram10 mg by mouth once per day for first 2 weeks, with psychiatric re-evaluation every 2 weeks to determine if any change in dosage is required, with a maximum of 20 mg per day | Drug | 1 Lexapro |
Primary outcome
Activations in Different Cortical Regions Caused by Emotionally Evocative Task
Time frame: baseline and week 8
MRI scans from 41 participants (23 depressed and 18 controls), including fMRI scans using an emotional distractor task, were analyzed for differences between groups in activation in a priori regions (amygdala and DLPFC), measured with BOLD signal, for two conditions of the task - attend fearful and ignore fearful, both at baseline and following 8 weeks of treatment for the depressed group. Voxel-wise comparisons (ANOVAs) were performed to determine differences in activations between groups within these regions. Positive values reflect a BOLD activation in that region; negative reflects a BOLD de-activation in that region. We expect more positive values (greater activation) in depressed participants at baseline than in controls during the attend fearful task, and more negative values (greater de-activation) in controls at baseline than depressed during the ignore fearful task. These differences were expected to lessen significantly following treatment in the depressed group.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 12893109Sheline YI. Neuroimaging studies of mood disorder effects on the brain. Biol Psychiatry. 2003 Aug 1;54(3):338-52. doi: 10.1016/s0006-3223(03)00347-0.
- Background: PubMed 18559283Fales CL, Barch DM, Rundle MM, Mintun MA, Mathews J, Snyder AZ, Sheline YI. Antidepressant treatment normalizes hypoactivity in dorsolateral prefrontal cortex during emotional interference processing in major depression. J Affect Disord. 2009 Jan;112(1-3):206-11. doi: 10.1016/j.jad.2008.04.027. Epub 2008 Jun 17.
- Background: PubMed 20534464Sheline YI, Price JL, Yan Z, Mintun MA. Resting-state functional MRI in depression unmasks increased connectivity between networks via the dorsal nexus. Proc Natl Acad Sci U S A. 2010 Jun 15;107(24):11020-5. doi: 10.1073/pnas.1000446107. Epub 2010 Jun 1.
- Results publication: PubMed 11704071Sheline YI, Barch DM, Donnelly JM, Ollinger JM, Snyder AZ, Mintun MA. Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment: an fMRI study. Biol Psychiatry. 2001 Nov 1;50(9):651-8. doi: 10.1016/s0006-3223(01)01263-x.
- Results publication: PubMed 17719567Fales CL, Barch DM, Rundle MM, Mintun MA, Snyder AZ, Cohen JD, Mathews J, Sheline YI. Altered emotional interference processing in affective and cognitive-control brain circuitry in major depression. Biol Psychiatry. 2008 Feb 15;63(4):377-84. doi: 10.1016/j.biopsych.2007.06.012. Epub 2007 Aug 24.
- Results publication: PubMed 19171889Sheline YI, Barch DM, Price JL, Rundle MM, Vaishnavi SN, Snyder AZ, Mintun MA, Wang S, Coalson RS, Raichle ME. The default mode network and self-referential processes in depression. Proc Natl Acad Sci U S A. 2009 Feb 10;106(6):1942-7. doi: 10.1073/pnas.0812686106. Epub 2009 Jan 26.
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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.
Yvette I. Sheline, MD principal investigator
University of Pennsylvania
Questions about this trial
What is this clinical trial studying?
A study testing Lexapro in people with Depression, run by Washington University School of Medicine.
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 4 inclusion and 6 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 17 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
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?
Yes. Results are posted in the registry (first posted 17 Jul 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Activations in Different Cortical Regions Caused by Emotionally Evocative Task (time frame: baseline and week 8). 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 NCT00749125, which also lists 6 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 17 Jul 2018.