fMRI Studies of Emotional Brain Circuitry in People With 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.

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.

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

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.

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

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