Neurocognitive Predictors of Behavioral Therapy Response in Depression

Brief Summary

Detailed Description

Anxiety and mood disorders are the most prevalent class of mental health disorders, with lifetime prevalence estimated at 32% and 18%, respectively. These disorders have tremendous personal and socioeconomic impacts (cost \>$1500 per-patient/year) due to days lost at work, increased health care utilization, and increased risk of mortality (e.g. cardiovascular disease). First-line treatments for depression include pharmacologic (e.g. selective serotonin reuptake inhibitors) and psychotherapeutic interventions (e.g. cognitive behavioral therapy and behavioral therapy). While both are superior to placebo treatments, only 40-60% of patients experience significant improvement and 15-25% of responders relapse within one year. Thus, long-lasting improvements are experienced by 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 aim of this study is to identify whether neural, biological, and behavioral responses related to the arbitration of conflicting avoidance and approach drives can predict behavior therapy response for depressed individuals. This aim 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 behavior therapy for depression (i.e., predictors of treatment effectiveness) and reveal targets for future treatment modifications. Aim 1: Clarify the potential contribution of approach-avoidance behaviors and neural responses to depression symptom severity. Hypothesis 1.1: Approach-related behaviors and conflict arbitration behavior will explain a significant amount of variance in depressive symptoms, above and beyond avoidance-related behavior. Hypothesis 1.2: Activations within approach-related (i.e., striatum) and conflict arbitration (i.e., lateral PFC) neural circuitry will explain significant variance in depressive symptom severity above and beyond activations within avoidance-related (i.e., amygdala) neural circuitry. Specifically, the investigators expect increased levels of depression to relate to reduced striatal responsivity. Aim 2: Identify approach-avoidance behaviors and neural responses that predict the effectiveness of behavioral activation therapy (BA) for depressed subjects. Hypothesis 2.1: Approach-related behaviors and/or conflict arbitration behavior will help predict treatment response above and beyond avoidance-related behavior and baseline symptom severity. Specifically, the investigators expect that decreased reward sensitivity will predict nonresponse of depressed patients to BA. Hypothesis 2.2: Approach-related and conflict arbitration neural circuitry will help to predict treatment response above and beyond activations within avoidance-related neural circuitry. Specifically, the investigators expect striatal responsivity to reward to predict response of depressed patients to BA. Aim 3: Identify whether functional improvement with BA is associated with change in approach-avoidance behaviors and/or neural responses. Hypothesis 3.1: The level of change in reward sensitivity will positively relate to the level of improvement in overall functioning with BA.

Primary Outcomes

Secondary Outcomes

• Change in depression-related behaviors as assessed by the Behavioral Activation Depression Scale (BADS) Short Form.(Trajectory of change from pre- to post- treatment; last time point assessed within 6 weeks following last treatment session, on average at 16 weeks after baseline assessment)
• Change in depressive symptoms as measured by the Beck Depression Inventory - II.(Change from pre- to post- treatment; last time point assessed within 6 weeks following last treatment session, on average at 16 weeks after baseline assessment)
• Change in anxiety symptoms as measured by the Patient Reported Outcomes Measurement Information System (PROMIS) Anxiety Scale.(Trajectory of change from pre- to post- treatment; last time point assessed within 6 weeks following last treatment session, on average at 16 weeks after baseline assessment)
• Change in level of disability as measured by the Sheehan Disability Scale(Trajectory of change from pre- to post- treatment; last time point assessed within 6 weeks following last treatment session, on average at 16 weeks after baseline assessment)