Approach-Avoidance Conflict-a Multi-level Predictor for Therapy Response
Condition: Generalized Anxiety Disorder
MeSH terms: Anxiety Disorders
Study type: Interventional

Summary: 
      This project aims to identify brain and behavioral characteristics of individuals
      experiencing symptoms of generalized anxiety disorder that will predict the effectiveness of
      Exposure-based therapy versus Behavioral Activation Therapy. Brain imaging aspects of the
      study will use functional magnetic resonance imaging (fMRI) and electroencephalography (EEG).
      Behavioral assessments will include self-report questionnaires, computer-based and
      observational tasks, and interviews. Assessments will focus on how individuals process
      positive information (such as reward) and negative information (such as distressing images),
      as well as how people make decisions. These assessments will be conducted across 2-3
      in-person sessions prior to beginning the treatment, and will be repeated across 2-3
      in-person sessions after completing treatment. A blood draw will also be conducted pre- and
      post- treatment. Both the Exposure-based and Behavior Activation therapy will consist of 10,
      90-minute weekly therapy sessions conducted in small groups.
    

Detailed description: 
      Generalized anxiety disorder (GAD) is the most common anxiety disorder in primary care, with
      lifetime prevalence rates of 6%. GAD leads to significant individual and socioeconomic burden
      (e.g., due to days lost at work and increased health care utilization). Although there is
      significant comorbidity with major depressive disorder (MDD), a GAD diagnosis conveys a much
      poorer prognosis, with only 58% with GAD vs. 80% with MDD alone obtaining remission in two
      years. This highlights the importance of effectively treating GAD, for improving mental and
      physical health and decreasing socioeconomic burden. First-line treatments include medication
      (e.g., selective serotonin reuptake inhibitors [SSRIs]) and psychotherapy (e.g., cognitive
      behavioral therapy [CBT]). While both are superior to placebo, only 40-60% experience
      significant improvement, with at least 25% relapsing within a year. Thus, long-lasting
      improvements are occurring in less than 50% of patients. This ineffectiveness has been
      moderately associated with symptom severity, illness duration, and comorbidity, but these
      findings do not provide any strategies for improving treatment effectiveness. The current
      study will seek to identify behavioral or cognitive-affective predictors that indicate how
      well a patient is responding to treatment so that interventions can be further individualized
      to more effectively treat refractory patients.

      The overall aim of this study are to identify whether neural, biological, and behavioral
      responses related to the arbitration of conflicting avoidance and approach drives can predict
      response to Exposure-based versus Behavioral Activate therapy for individuals with
      generalized anxiety disorder (with or without co-morbid major depressive disorder). This will
      be accomplished using behavioral, functional magnetic resonance imaging (fMRI), and genetic
      analyses pre and post Behavioral Activation therapy. Research subjects will include
      treatment-seeking individuals with clinically significant symptoms of unipolar depression.
      Diagnosis will be assessed using structured clinical interviews. Anxious and depressive
      symptom severity, personality characteristics, and general functioning will be collected via
      self-report paper-and-pencil questionnaires. Objective measures of approach, avoidance, and
      conflict behavioral responses will be collected using computer-administered testing and
      related neural responsivity will be measured using fMRI. For exploratory aims, a blood draw
      will be collect pre and post-treatment to examine genetic factors that may predict response
      to behavior therapy. This research has the potential to identify neural and behavioral
      approach-avoidance characteristics that can help predict which patients are likely to respond
      to Exposure-based versus Behavioral Activation therapy (i.e., predictors of treatment
      effectiveness) and reveal targets for future treatment modifications.

      Aim 1: Examine relationships among approach-avoidance behavior and neural responses, and
      baseline GAD symptom severity.

      Hypothesis 1.1: Approach and conflict arbitration behavior will explain significant variance
      in baseline symptoms above and beyond avoidance-related behavior.

      Hypothesis 1.2: Approach (striatum) and conflict arbitration (lateral PFC) neural activity
      will explain significant variance in baseline symptoms above and beyond avoidance-related
      (amygdala) neural activity.

      Aim 2: Examine how multi-level approach-avoidance behavior and neural responses predict
      individualized response to Exposure-based therapy for GAD (compared to Behavioral
      Activation).

      Hypothesis 2.1: Approach-related and conflict arbitration behavior will help predict
      treatment response above and beyond avoidance-related behavior and baseline symptom severity.

      Hypothesis 2.2: Activity in approach-related and conflict arbitration neural circuitry will
      predict treatment response above and beyond activity in avoidance-related neural circuitry.

      Aim 3: Identify the changes in approach-avoidance processes that relate to Exposure therapy
      elicited functional improvement (compared to Behavioral Activation).

      Hypothesis 3.1: The degree to which conflict arbitration abilities increase with treatment
      will positively relate to functional improvement from pre- to post-treatment.
    

Intervention name(s): Exposure-based therapy; Behavioral Activation therapy; Computer-based behavioral assessment; Surveys and Interviews; Magnetic resonance imaging (MRI); Electroencephalography (EEG)
Intervention type(s): Behavioral; Behavioral; Behavioral; Behavioral; Device; Device
Intervention description(s): Exposure-based therapy; Behavioral Activation therapy; Computer-based tasks during which participants respond to images on the screen, including abstract images, emotional faces, and pleasant and unpleasant images.; Surveys and interviews in which participants will be asked to answer questions related to their mental and physical health history and current symptoms.; Magnetic resonance imaging (MRI) will be used to obtain information concerning the structure of the brain, as well as to assess changes associated with blood flow in the brain while participants are completing behavioral tasks (see description of computer-based behavioral assessment intervention).; Electroencephalography (EEG) will be used to assess changes in the electrical activity of the brain while participants are completing behavioral tasks (see description of computer-based behavioral assessment intervention).
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science