Although cognitive behavioral therapy (CBT) is an efficacious first-line intervention for individuals with affective disorders, non-responder rates remain high. Repetitive negative thinking (RNT; i.e., mental rituals, worries, depressive ruminations) predicts poor treatment outcome and is a common residual symptom following CBT. Thus, there is an urgent unmet need to identify the mechanistic targets underlying RNT to optimize treatment response and reduce the psychiatric burden and healthcare costs for patients with affective disorders. Given that a hallmark feature of RNT is the difficulty controlling and disengaging from perseverative thought, recent theoretical models propose that deficits in attentional and cognitive control underlie RNT as fundamental biobehavioral targets. Yet studies validating these targets are lacking. This five-year Mentored Patient-Oriented Research Career Development Award will address this need. Specifically, this project will test the hypothesis that enhancing attention regulation skills in a transdiagnostic intervention streamlined and adapted for RNT ? Emotion Regulation Therapy-Attention Regulation (ERT-AR) ? will significantly improve the proposed target of attentional/cognitive control relative to a supportive psychotherapy (SPT) control group as measured by multi- method target indices: (a) behavioral (i.e., disengagement and sustained attention in the presence of emotional stimuli measured by eye tracking fixations and reaction time), (b) electrophysiological (i.e., proactive and reactive cue- and target-locked N2, N450, and P300 event related potentials in a cued conflict monitoring task), and (c) self-report (i.e., perceived ability to shift and focus attention). We also will examine early signs of treatment efficacy, predicting that ERT-AR will improve RNT and psychiatric functioning outcomes (symptom severity, functional impairment) relative to SPT, and target validation (i.e., changes in attentional/cognitive control will correlate with changes in RNT and associated symptoms).
Study aims correspond to specific training goals for the candidate (Dr. Ryan Jacoby) in four key areas that will launch her as an independent translational clinical scientist: (1) affective neuroscience and measurement of biobehavioral targets, (2) clinical trials and experimental therapeutics methodology, (4) advanced longitudinal statistics, and (5) career development. Training goals will be implemented with the expert guidance of Dr. Sabine Wilhelm (primary mentor), co-mentors Drs. Diego Pizzagalli and Douglas Mennin, and advisors Drs. Dan Dillon, Rudi De Raedt, and David Schoenfeld. At baseline, we will assess clinical symptoms and administer well-validated attentional and cognitive control paradigms. Patients with RNT will then be provided 8 sessions of ERT-AR or SPT and will be re-administered assessments at weeks 4 and 8. We will examine changes in our target indices during treatment, as well as changes in outcomes over treatment and 3-month follow-up. If our hypotheses are supported, we will identify a cross-cutting target that can be engaged to optimize treatment response for individuals with elevated RNT, enhancing the generalizability of our findings for maximum public health impact.

Public Health Relevance

Repetitive negative thinking (RNT) is a core cognitive process central to the etiology and maintenance of many forms of psychopathology. Given that the presence of RNT undermines treatment outcomes, an urgent unmet need is to understand the precise psychological targets and neural systems underlying RNT that could be engaged in treatment. Thus, this project takes an experimental therapeutics approach to assess: (a) target engagement of attentional/cognitive control (as measured by eye tracking, event related potentials, and self- report data), (b) preliminary treatment efficacy of a transdiagnostic treatment for elevated RNT optimized to address attention regulation, and (c) whether improvements in attentional/cognitive control are associated with improved RNT and disorder-specific symptoms (i.e., target validation).

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Mentored Patient-Oriented Research Career Development Award (K23)
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Special Emphasis Panel (ZMH1)
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Chavez, Mark
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Massachusetts General Hospital
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