Mechanisms for Behavior Change and Maintenance of Treatment for CKD Comorbid Depression

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Project Summary/Abstract The purpose of this application is to understand why interventions for the treatment of Major Depressive Disorder (MDD) work or do not work initially and over time in patients with Chronic Kidney Disease (CKD). This project will add assessments to my ongoing NIH R01-funded study (R01DK124379-05), Combination of Novel Therapies for CKD Comorbid Depression, to help illuminate mechanisms of action mediating response to treatment; facilitators and barriers to adoption of treatment; and maintenance of treatment response. We will collect complimentary data that will use information from the subset of participants who have completed the parent study to investigate mechanisms for depression treatment effect, or lack thereof, and also identify the maintenance of treatment effect beyond the active intervention period in those who initially have remission in depression after 8 weeks of treatment. In the parent R01 study, we are currently comparing the efficacy of two 16-week strategies vs. control for treatment of MDD starting with (1) Behavioral Activation Therapy (BAT) or (2) bupropion drug therapy, each augmented to a combination of both in non-remitters after 8 weeks. We will engage the subset of participants that have completed the parent trial to: Aim 1. Identify mechanisms of action of intervention effect, vs. lack thereof, by identifying candidate inflammatory mediators/moderators of MDD treatment response in CKD patients. We will use (a) RNA-Sequencing of whole blood gene expression and (b) plasma inflammatory biomarkers from frozen samples that have already been collected at baseline and at week 8 from patients who completed at least 8 weeks from the parent study (N =76). We will evaluate whether there is a modification from baseline in candidate innate immune activation/inflammatory pathways through targeted whole genomic transcriptional profiling and plasma biomarkers in (a) depression remitters (defined as Quick Inventory of Depressive Symptomatology score - QIDS-SR ≤5) vs. non-remitters; and (b) responders to treatment (defined as a decrease in the QIDS-SR score by ≥3 points from baseline) vs. non-responders to treatment. Aim 2. Assess underlying facilitators of or barriers to behavior adoption, in this case adherence to MDD treatment interventions (drug by pill count and BAT teletherapy sessions), in patients with CKD. We will conduct focus groups in 50 participants who have finished the 16-week trial to gather data on participants’ experiences, barriers to and facilitators of intervention engagement and adherence, and perceived benefits of the intervention. Aim 3. Assess maintenance of MDD treatment response over time, beyond the 16-week active intervention period (N =50), in remitters vs. non-remitters at 8 weeks, by assessing improvement in patient-centered outcomes of (a) depressive symptoms; (b) fatigue; (c) sleep; (d) overall functioning. This application corresponds with my parent R01’s scope and timeline and the purpose and requirements of the Office of Behavioral and Social Sciences Research. The aims will not interfere and do not overlap with the original scope of the parent R01.