Depression
Conditions
Keywords
Emotional Circuitry, fMRI
Brief 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.
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.
Interventions
DRUGLexapro
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
Sponsors
National Institute of Mental Health (NIMH)
Washington University School of Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
Depressed: Inclusion Criteria: * 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Activations in Different Cortical Regions Caused by Emotionally Evocative Task | 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. |
Participant flow
Recruitment details
2004-2009. Participants from Washington University in St. Louis.
Pre-assignment details
99 participants started the study and were assigned to either the depressed or control group.
Participants by arm
| Arm | Count |
|---|---|
| 1 Lexapro The depressed participants in this arm will be given Lexapro.
Lexapro: 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.
At both the initial and follow-up fMRI (functional magnetic resonance imaging) study visits, images of brain function and anatomy will be recorded. | 52 |
| 2 Control The nondepressed participants in this arm will not be given any intervention for depression.
At both the initial and follow-up fMRI (functional magnetic resonance imaging) study visits, images of brain function and anatomy will be recorded. | 47 |
| Total | 99 |
Baseline characteristics
| Characteristic | 1 Lexapro | Total | 2 Control |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 52 Participants | 99 Participants | 47 Participants |
| Age, Continuous | 36.04 years STANDARD_DEVIATION 9.605 | 34.2 years STANDARD_DEVIATION 9.1 | 32.15 years STANDARD_DEVIATION 8.228 |
| Region of Enrollment United States | 52 participants | 99 participants | 47 participants |
| Sex: Female, Male Female | 30 Participants | 58 Participants | 28 Participants |
| Sex: Female, Male Male | 22 Participants | 41 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 51 | 0 / 48 |
| other Total, other adverse events | 0 / 51 | 0 / 48 |
| serious Total, serious adverse events | 0 / 51 | 0 / 48 |
Outcome results
Primary
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.
Time frame: baseline and week 8
Population: 23 patients with major depression were matched with 18 demographically similar healthy controls. Depressed subjects were treated with Lexapro 10 mg/day, initiated immediately following the first fMRI scan.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1 Lexapro | Activations in Different Cortical Regions Caused by Emotionally Evocative Task | Time 2 - Amygdala - Ignore fearful | -0.031 Voxels | Standard Deviation 0.214 |
| 1 Lexapro | Activations in Different Cortical Regions Caused by Emotionally Evocative Task | Time 2 - Amygdala - attend fearful | -0.031 Voxels | Standard Deviation 0.264 |
| 1 Lexapro | Activations in Different Cortical Regions Caused by Emotionally Evocative Task | Baseline - DLPFC - attend fear | 0.072 Voxels | Standard Deviation 0.092 |
| 1 Lexapro | Activations in Different Cortical Regions Caused by Emotionally Evocative Task | Baseline - Amygdala - ignore fear | 0.021 Voxels | Standard Deviation 0.19 |
| 1 Lexapro | Activations in Different Cortical Regions Caused by Emotionally Evocative Task | Time 2 - DLPFC - Attend fearful | 0.026 Voxels | Standard Deviation 0.134 |
| 1 Lexapro | Activations in Different Cortical Regions Caused by Emotionally Evocative Task | Baseline - DLPFC - ignore fear | 0.063 Voxels | Standard Deviation 0.129 |
| 1 Lexapro | Activations in Different Cortical Regions Caused by Emotionally Evocative Task | Time 2 - DLPFC - Ignore fearful | 0.091 Voxels | Standard Deviation 0.161 |
| 1 Lexapro | Activations in Different Cortical Regions Caused by Emotionally Evocative Task | Baseline - Amygdala - attend fear | -0.021 Voxels | Standard Deviation 0.128 |
| 2 Control | Activations in Different Cortical Regions Caused by Emotionally Evocative Task | Time 2 - DLPFC - Ignore fearful | 0.109 Voxels | Standard Deviation 0.123 |
| 2 Control | Activations in Different Cortical Regions Caused by Emotionally Evocative Task | Baseline - Amygdala - attend fear | 0.084 Voxels | Standard Deviation 0.135 |
| 2 Control | Activations in Different Cortical Regions Caused by Emotionally Evocative Task | Baseline - Amygdala - ignore fear | -0.030 Voxels | Standard Deviation 0.146 |
| 2 Control | Activations in Different Cortical Regions Caused by Emotionally Evocative Task | Baseline - DLPFC - attend fear | -0.025 Voxels | Standard Deviation 0.132 |
| 2 Control | Activations in Different Cortical Regions Caused by Emotionally Evocative Task | Baseline - DLPFC - ignore fear | 0.073 Voxels | Standard Deviation 0.086 |
| 2 Control | Activations in Different Cortical Regions Caused by Emotionally Evocative Task | Time 2 - Amygdala - attend fearful | -0.032 Voxels | Standard Deviation 0.178 |
| 2 Control | Activations in Different Cortical Regions Caused by Emotionally Evocative Task | Time 2 - Amygdala - Ignore fearful | -0.041 Voxels | Standard Deviation 0.161 |
| 2 Control | Activations in Different Cortical Regions Caused by Emotionally Evocative Task | Time 2 - DLPFC - Attend fearful | 0.075 Voxels | Standard Deviation 0.121 |