Serotonin Transporter Genetic Variation and Amygdalar Activation Correlates of Antidepressant Response
The purpose of this study is to find out what parts of the brain have increased or decreased activity when people are depressed and how antidepressant medicine changes this activity in depressed patients.In particular, this study will investigate whether variation in the serotonin transporter gene can affect the response to escitalopram as measured by clinical interview and MRI scan. We will measure activity in different parts of the brain, while subjects see pictures, using Magnetic Resonance Imaging (MRI) scan. There will be three MRI scans; one before we start any medication, one during the study after 3 weeks of treatment and one after six more weeks of treatment. Treatment will consist of Escitalopram. Additionally a blood sample will be taken for genetic testing. The genetic samples collected are to look at variation in a gene (serotonin transporter gene), which affects the functioning of the chemical serotonin in the brain.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Serotonin Transporter Genetic Variation and Amygdalar Activation Correlates of Antidepressant Response|
- Decrease in amygdalar activation and increase in cortico-amygdala connectivity as shown by fMRI given at baseline and three weeks from baseline and nine weeks from baseline [ Time Frame: Started: July 2003 ended August 2007 ] [ Designated as safety issue: No ]
- Improvement in scores on Hamilton Depression Rating Scale [ Time Frame: Started July 2003 Ended August 2007 ] [ Designated as safety issue: No ]
- Improvement in scores on the Hamilton Anxiety Rating Scale [ Time Frame: Started July 2003 ended August 2007 ] [ Designated as safety issue: No ]
|Study Start Date:||July 2003|
|Study Completion Date:||August 2007|
|Primary Completion Date:||August 2007 (Final data collection date for primary outcome measure)|
Hypothesis 1: Depressed patients with the s/s or s/L alleles of the 5-HTTLPR polymorphism will have greater amygdalar activation and decreased cortico-amygdala connectivity compared to patients with L/L genotype
Hypothesis 2: After 2 and 8 weeks of treatment with escitalopram (10 mg) depressed patients with the L/L allele will have a greater decrease in amygdalar activation and a greater increase in cortico-amygdala connectivity than patients with s/s or s/L genotypes.
We will stratify the subjects in the two genotype groups so that they are comparable in terms of age and gender distributions. Only depressed patients will be treated with escitalopram. Healthy subjects and unmedicated currently euthymic depressed patients will have baseline scan and subsequent repeat fMRI scans at the same intervals as the depressed patients but will not receive any treatment. After completing the first fMRI scan, depressed patients will undergto one week of single blind placebo lead in. After the first week patient's depression symptoms will be assessed again. If depression symptoms are much better after the first week ( > 20% reduction in HAM-D scores) then the patient will not be asked to do the rest of the study and will be referred to a clinician of their choice for further treatment as necessary. If their depression symptoms do not show much improvement after the first week then they will be asked to take escitalopram for the next 8 weeks. At the end of 3 weeks of treatment from baseline, the patient will undergo a second fMRI scan. Following the second fMRI scan the patient will be continued on escitalopram for another 6 weeks.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00456430
|United States, Indiana|
|Indiana University Adult Psychiatry Clinic|
|Indianapolis, Indiana, United States, 46202|
|Principal Investigator:||Amit Anand, MD||Indiana University School of Medicine|