Serotonin Transporter Genetic Variation and Amygdalar Activation Correlates of Antidepressant Response
Condition: Depression
MeSH terms: Depression
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    

Detailed description: 
      Hypotheses:

      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.

      Methods:

      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.
    

Intervention name(s): Escitalopram
Intervention type(s): Drug
Intervention description(s): 10 mg a day of escitalopram by mouth per day for 4 weeks. Dose may be increased to 20 mg a day after the 4th week depending on tolerance and treatment response.
Other intervention name(s): lexapro
Intervention MeSH terms: Escitalopram
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment