Approach-Avoidance Conflict-a Multi-level Predictor for Therapy Response

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. The statistical analysis plan was described within a protocol paper published in 2020 (Santiago et al., 2020), which is cited in the References section.