Neural mechanisms and predictors of SSRI and CBT treatment of anxiety: A randomized trial focused on emotion and cognitive processing

Anxiety disorders (ADs) are common and difficult to treat. While research suggests ADs are characterized by an imbalance between bottom-up and top-down attention processes and that effective treatments work by correcting this dysfunction, there is insufficient data to explain how and for whom treatments work. The late positive potential (LPP), an event-related potential reflecting elaborative processing of motivationally salient stimuli, is sensitive to both bottom-up and top-down processes. The present study examines the LPP in healthy controls (HC) and patients with ADs under low and high working memory (WM) load to assess its utility as a predictor and index of symptom reduction in patients who underwent cognitive behavioral therapy (CBT) or selective serotonin reuptake inhibitor (SSRI) treatment. The LPP when viewing negative and neutral distractor images and WM performance were assessed in 96 participants (40 HC, 32 CBT, 24 SSRI) during a letter recall task at Week 0 and in a subset of the study sample (23 CBT, 16 SSRI) at Week 12. Patients were randomly assigned to twelve weeks of CBT or SSRI treatment. Participants completed self-reported symptom measures at each time point. Greater Week 0 LPP to negative images under low WM load predicted greater symptom reduction in the SSRI, but not the CBT, group. Regression analyses examining the LPP to negative images as an index of symptom reduction revealed a smaller decrease in the LPP to negative images under low WM load was associated with less anxiety reduction across treatment modalities. Findings suggest the LPP during low WM load may serve as a cost-effective predictor and index of treatment outcome in ADs. Clinical Trials Registration: ClinicalTrials.gov (Identifier: NCT01903447).