fMRI Study of Treatment Changes in Major Depression

Study Overview
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Brief Summary
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The overall purposes of this research are to determine if Cognitive Behavioral Therapy (CBT) has the same healing effect on the brain for people with depression as traditional antidepressants do, and in comparison to healthy controls with no history of depression, to find out more about the causes of depression including differences in the extent of problems caused by depression. We hypothesize that CBT will have the same healing effect on the brain as antidepressants; that differences in brain activations created by the various tasks and genetic differences will help us understand differences in the type and severity of symptoms among the depressed subjects.

Detailed Description
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The overall purposes of this research are to determine if Cognitive Behavioral Therapy (CBT) has the same healing effect on the brain for people with depression as traditional antidepressants do, to find out more about the causes of depression and why people differ in the extent of problems caused by depression, and to determine if certain differences in genes within populations are related to clinical symptoms.Genes we are examining for this study are COMT, BDNF, and 5-HTT long arm and short arm, as well as future genes that may be discovered to play a role in depression at a later time, and will be determined by examining saliva and blood samples. We are primarily studying depression by functional Magnetic Resonance Imaging (fMRI) which allows us to identify certain parts of the brain that show how the brain works in controlling negative feelings. Participants will be imaged while performing different tasks that are believed to activate emotional circuitry of the brain. Comparisons of activation patterns across these tasks will be used to characterize the cognitive mechanisms supported by different cortical regions, and to determine patterns of functional brain deficits in subjects with depression. Comparisons will also be made between changes that occur after treatment with an approved antidepressant and treatment with CBT.

Official Title
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fMRI Studies of Emotional Circuitry in Major Depression: Treatment Changes

Conditions
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Treatment, Major Depression

Intervention / Treatment
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* Drug: Sertraline
* Behavioral: Cognitive Behavioral Therapy


Participation Criteria
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Eligibility Criteria
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DEPRESSED GROUP: Inclusion criteria: Age 18-50 DSM-IV criteria for major depressive disorder (MDD) Minimum Hamilton Rating Scale for Depression (HAMD) score > 18 Right handed Capacity to give informed consent and follow study procedures English speaking Exclusion criteria: Cannot give informed consent Significant handicaps (e.g. visual or hearing loss, mental retardation) that would interfere with testing procedures Does not speak English Known primary neurological disorders Any other factor that in the investigators judgment may affect patient safety or compliance (e.g. distance greater than 100 miles from clinic) MRI contraindications e.g. foreign metallic implants, pacemaker Known allergy or hypersensitivity to sertraline Active suicidality Severe or unstable medical illness or conditions or drugs that may cause depression Any of the following diagnosed by DSM-IV: alcohol or substance abuse disorder, schizophrenia or other psychotic disorder, bipolar disorder, psychotic features of depression, current obsessive compulsive disorder (OCD) or panic disorder. In general, subjects with a history of other Axis I disorders prior to their depression will be excluded. Current episode has failed to respond to adequate trials of two prior antidepressants for at least 6 weeks at therapeutic doses. Treatment with sertraline for at least one month in past 3 months. Current use of psychotropic prescription or nonprescription drugs or herbals (e.g. hypericum) except for limited use of certain hypnotics. Current psychotherapy Treatment with psychotropic drugs or drugs that affect the CNS such as beta-blockers or mood stabilizers. CONTROL GROUP: Inclusion criteria: Age 18-50 No history of MDD HAMD score < 7 Right handed Capacity to give informed consent and follow study procedures English speaking Exclusion criteria: Cannot give informed consent Significant handicaps (e.g. visual or hearing loss, mental retardation) that would interfere with testing procedures Does not speak English Known primary neurological disorders Any other factor that in the investigators judgment may affect patient safety or compliance (e.g. distance greater than 100 miles from clinic) MRI contraindications e.g. foreign metallic implants, pacemaker Severe or unstable medical illness or conditions or drugs that may cause depression Any of the following diagnosed by DSM-IV: alcohol or substance abuse disorder, schizophrenia or other psychotic disorder, bipolar disorder, major depression, OCD or panic disorder. Current use of psychotropic prescription or nonprescription drugs or herbals (e.g. hypericum) except for limited use of certain hypnotics. Treatment with psychotropic drugs or drugs that affect the CNS such as beta-blockers or mood stabilizers.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Depressed Group: CBT<br>Depressed participants randomized to receive Cognitive Behavioral Therapy (CBT) for treatment. A fMRI scan session will occur immediately prior to starting treatment, and their second fMRI scan will occur immediately following the completion of 12 weeks of therapy. | Behavioral: Cognitive Behavioral Therapy<br>* Depressed participants will be randomized to SRT or CBT treatment. For those in the CBT treatment condition, visits for the CBT sessions will occur on or about Day = 3,Day = 7,Day = 10,Day 14, Day 21, Day 28, Day 35, Day 42, Day 49, Day 56, Day 63, Day 70, Day 77, and Day 84. Visits to check for progress and administer the Hamilton Depression rating scale will occur at Day = 0 and on or about Day = 14, Day 28, Day 42, Day 56, Day 70 and Day 84. Depressed subjects will start their CBT treatment once their first MRI and computer testing sessions are completed.<br>* Other names: CBT;|
| No Intervention: Healthy Control Group<br>Healthy controls will an fMRI scan session and their second fMRI scan session will occur approximately 12 weeks after. | |
| Active Comparator: Depressed Group: SRT<br>Depressed participants randomized to receive the antidepressant sertraline (SRT) for treatment. A fMRI scan session will occur immediately prior to starting treatment, and their second fMRI scan will occur immediately following the completion of 12 weeks of therapy. | Drug: Sertraline<br>* Depressed participants will be randomized to SRT or CBT treatment. For those in the SRT treatment condition, visits will involve dispensing medications, checking for side effects and administering the Hamilton Depression rating scale occurring at Day = 0 and on or about Day = 14, Day 28, Day 42, Day 56, Day 70 and Day 84. Depressed patients treated with SRT will titrate up to a maximum dose of 200 mg daily depending on tolerability and inadequate antidepressant response. Depressed subjects will start their SRT treatment once their first MRI and computer testing sessions are completed.<br>* Other names: SRT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood Oxygen-level Dependent Activations During an Emotional Distractor Task Between fMRI Scans of Depressed Participants in the CBT Group and Control Participants. | MRI imaging was completed on 50 participants (26 depressed who were randomized to the CBT group and 24 controls) for this analysis, including fMRI scans to evaluate regional brain activation in depression during an emotional distractor task. Image data from their baseline visit was processed and analyzed to show differences in blood oxygen-level dependent (BOLD) activations between depressed participants in the CBT group and control participants in a priori regions (amygdala and dorsolateral prefrontal cortex) during the task. The specified regions were masked on the images, and voxel-wise comparisons (ANOVAs) were performed to determine differences in activations between groups within these masked regions Positive values reflect a BOLD activation in that region; negative reflects a BOLD de-activation in that region. | baseline visit and 8-week follow-up | 
| Hamilton Depression Rating Scale Score at Baseline and 12 Weeks | The patient was rated by a research team member among 17 dimensions/items pertaining to depression symptoms experienced over the last week. Each item is scored from 0 (=absent), up to 2 or 4 (depending on the item). The maximum total score on the assessment, indicating the most severe depression, would be 52. A total score of 0-7 is considered to be normal. Total scores of 20 or higher indicate moderate, severe, or very severe depression. A 50% or greater drop in Hamilton Depression Rating Scale signifies response to treatment. | Baseline and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Major Depression, Functional Magnetic Resonance Imaging, Emotional Circuitry, Cognitive Behavioral Therapy