Identifying Brain and Genetic Markers of Sertraline Treatment Response in People With Social Anxiety Disorder

Neuro-Genetic Markers of SSRI Treatment Response in Social Anxiety Disorder

This study will attempt to identify gene and brain activity markers that predict whether people with social anxiety disorder will respond to selective serotonin reuptake inhibitor medications.

Study Overview

• Status: Completed
• Conditions: Anxiety Disorders
• Intervention / Treatment: Drug: Sertraline

Detailed Description

Social anxiety disorder (SAD) is an anxiety disorder characterized by excessive fear and avoidance of social situations. Selective serotonin reuptake inhibitors (SSRIs) are a medication commonly prescribed to treat social anxiety disorder, but as many as 50% of people with SAD do not respond to SSRIs. Current theory suggests that neurological functioning and genetics may influence a patient's response to treatment. This study will examine variations in genetics and brain reactivity among people with SAD who do and do not respond to SSRIs. Through this, the study will identify neurological and genetic biomarkers that can predict responsiveness to SSRI treatment in people with SAD.

Participation in this study will last 14 weeks. Both healthy people and people with SAD will be recruited to participate. All participants will complete similar study visits at entry, within 2 weeks of entry, and 12 weeks after that. The first visit, which will occur at study entry, will include screening questionnaires, an interview with research staff, a medical screening, a urine test, and collection of saliva samples for genotyping. The second visit and the last visit, which will be separated by 12 weeks, will involve MRI scans and behavioral tasks to be conducted inside and outside the MRI scanner. Over the 12 weeks between MRI scanning sessions, participants with SAD will take sertraline, a common SSRI, on a daily basis. They will also attend five additional visits during this time to complete assessments of their symptoms. These visits will occur 1, 2, 4, 8, and 12 weeks after starting sertraline treatment. Participants with SAD will therefore be completing a symptom assessment, MRI scans, and behavioral tasks all on the final visit, 12 weeks after the second visit.

• Study Type: Observational
• Enrollment (Actual): 200

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Community and outpatient clinic samples

Description

Inclusion Criteria:

For social anxiety disorder group:

• Current diagnosis of social anxiety disorder, generalized subtype
• Physically healthy, as confirmed by comprehensive medical history, physical exam, and laboratory testing

For healthy control group:

• Never been diagnosed with either Axis I or Axis II mental disorders
• Physically healthy, as confirmed by comprehensive medical history, physical exam, and laboratory testing

Exclusion Criteria:

• Clinically significant medical or neurologic condition
• Diagnosis of primary comorbid anxiety disorder, defined by which disorder is the more debilitating and clinically salient
• History of bipolar disorder or schizophrenia
• Presence of an organic mental syndrome, mental retardation, or pervasive developmental disorder
• Current major depressive disorder or major depression within the past 6 months
• Hamilton Rating Scale for Depression score greater than 18
• Alcohol or drug abuse or dependence within the past year
• Current suicidal ideation
• Diagnosis of an Axis II personality disorder, except for avoidant personality disorder
• Treatments with psychotropic or psychoactive medications within the 2 weeks before screening (or 8 weeks for fluoxetine and 4 weeks for monoamine oxidase inhibitors)
• Positive urine drug screen results
• Pregnancy

Additional exclusion criteria for the functional MRI studies:

• Left-handedness, as determined by standard questionnaire
• Presence of ferrous-containing metals within the body, such as aneurysm clips, shrapnel, or retained particles
• Claustrophobia

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Generalized social anxiety disorder participants; Participants with generalized social anxiety disorder will undergo MRI scanning and sertraline treatment.	Drug: Sertraline; Oral sertraline will begin at 50 mg per day, then increase to 75 mg per day on Day 8, then increase to 100 mg per day on Day 15. The dose may be increased to 150 mg per day on Week 8, based on clinical response and medication toleration.; Other Names: Zoloft
Healthy control participants; Healthy control participants will undergo MRI scanning.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Clinical Global Impression (CGI) Scale	Measured before treatment, at five treatment study visits, and 12 weeks after starting treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Liebowitz Social Anxiety Scale (LSAS)	Measured before treatment, at five treatment study visits, and 12 weeks after starting treatment

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: K. Luan Phan, MD, University of Michigan

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): May 1, 2011
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: March 30, 2009
• First Submitted That Met QC Criteria: March 30, 2009
• First Posted (Estimate): March 31, 2009

Study Record Updates

• Last Update Posted (Estimate): November 23, 2011
• Last Update Submitted That Met QC Criteria: November 21, 2011
• Last Verified: November 1, 2011

More Information

Terms related to this study

• Keywords: Anxiety; Social Phobia; Generalized Social Anxiety Disorder
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Phobic Disorders; Disease; Anxiety Disorders; Phobia, Social; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Sertraline
• Other Study ID Numbers: K23MH076198 (U.S. NIH Grant/Contract); DAHBR 9A-ASPI; 5K23MH076198 (U.S. NIH Grant/Contract)