fMRI Study of Treatment Changes in Major Depression

• ClinicalTrials.gov Identifier: NCT01027559
• Recruitment Status: Completed
• First Posted: December 8, 2009
• Results First Posted: June 13, 2018
• Last Update Posted: July 17, 2018
• Sponsor: Washington University School of Medicine
• Collaborator: National Institute of Mental Health (NIMH)
• Information provided by (Responsible Party): Washington University School of Medicine

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Major Depression; Treatment	Drug: Sertraline; Behavioral: Cognitive Behavioral Therapy	Not Applicable

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 97 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Other
• Official Title: fMRI Studies of Emotional Circuitry in Major Depression: Treatment Changes
• Study Start Date: February 2009
• Actual Primary Completion Date: January 2014
• Actual Study Completion Date: January 2014

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Depressed Group: CBT; 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; 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.; Other Name: CBT
No Intervention: Healthy Control Group; Healthy controls will an fMRI scan session and their second fMRI scan session will occur approximately 12 weeks after.
Active Comparator: Depressed Group: SRT; 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; 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.; Other Name: SRT

Outcome Measures

Primary Outcome Measures :

1. Blood Oxygen-level Dependent Activations During an Emotional Distractor Task Between fMRI Scans of Depressed Participants in the CBT Group and Control Participants. [ Time Frame: baseline visit and 8-week follow-up ]
   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.
2. Hamilton Depression Rating Scale Score at Baseline and 12 Weeks [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

DEPRESSED GROUP:

Inclusion criteria:

1. Age 18-50
2. DSM-IV criteria for major depressive disorder (MDD)
3. Minimum Hamilton Rating Scale for Depression (HAMD) score > 18
4. Right handed
5. Capacity to give informed consent and follow study procedures
6. English speaking

Exclusion criteria:

1. Cannot give informed consent
2. Significant handicaps (e.g. visual or hearing loss, mental retardation) that would interfere with testing procedures
3. Does not speak English
4. Known primary neurological disorders
5. Any other factor that in the investigators judgment may affect patient safety or compliance (e.g. distance greater than 100 miles from clinic)
6. MRI contraindications e.g. foreign metallic implants, pacemaker
7. Known allergy or hypersensitivity to sertraline
8. Active suicidality
9. Severe or unstable medical illness or conditions or drugs that may cause depression
10. 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.
11. Current episode has failed to respond to adequate trials of two prior antidepressants for at least 6 weeks at therapeutic doses.
12. Treatment with sertraline for at least one month in past 3 months.
13. Current use of psychotropic prescription or nonprescription drugs or herbals (e.g. hypericum) except for limited use of certain hypnotics.
14. Current psychotherapy
15. Treatment with psychotropic drugs or drugs that affect the CNS such as beta-blockers or mood stabilizers.

CONTROL GROUP:

Inclusion criteria:

1. Age 18-50
2. No history of MDD
3. HAMD score < 7
4. Right handed
5. Capacity to give informed consent and follow study procedures
6. English speaking

Exclusion criteria:

1. Cannot give informed consent
2. Significant handicaps (e.g. visual or hearing loss, mental retardation) that would interfere with testing procedures
3. Does not speak English
4. Known primary neurological disorders
5. Any other factor that in the investigators judgment may affect patient safety or compliance (e.g. distance greater than 100 miles from clinic)
6. MRI contraindications e.g. foreign metallic implants, pacemaker
7. Severe or unstable medical illness or conditions or drugs that may cause depression
8. 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.
9. Current use of psychotropic prescription or nonprescription drugs or herbals (e.g. hypericum) except for limited use of certain hypnotics.
10. Treatment with psychotropic drugs or drugs that affect the CNS such as beta-blockers or mood stabilizers.

Contacts and Locations

Locations

United States, Missouri

Washington University

Saint Louis, Missouri, United States, 63110

Sponsors and Collaborators

Washington University School of Medicine

National Institute of Mental Health (NIMH)

Investigators

• Principal Investigator: Yvette I Sheline, MD; University of Pennsylvania
• Principal Investigator: Charles Conway, MD; Washington University School of Medicine

More Information

• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT01027559
• Other Study ID Numbers: 081348; R01MH064821 ( U.S. NIH Grant/Contract ); 2R01MH064821-05A2 ( U.S. NIH Grant/Contract ); DDTR A3-NSI ( Other Grant/Funding Number: National Institute of Mental Health )
• First Posted: December 8, 2009
• Results First Posted: June 13, 2018
• Last Update Posted: July 17, 2018
• Last Verified: June 2018

Keywords provided by Washington University School of Medicine:

Major Depression; Functional Magnetic Resonance Imaging; Emotional Circuitry; Cognitive Behavioral Therapy

Additional relevant MeSH terms:

Depression; Depressive Disorder; Depressive Disorder, Major; Behavioral Symptoms; Mood Disorders; Mental Disorders; Sertraline; Antidepressive Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Serotonin Agents; Physiological Effects of Drugs