Engaging Higher-Order Mechanisms of Psychopathology: A Parsimonious Approach to Precision Medicine

Grants and Contracts Details


PROJECT SUMMARY/ABSTRACT Despite considerable investments in treatment development for psychological conditions, response rates for most interventions are quite modest (30-40%)2,3 and the prevalence of mental disorders remains persistently high.4 A new approach to psychological treatment is clearly needed to move the needle on the disease burden of mental illness. In the last decade, researchers have identified a manageable number of personality dimensions (i.e., neuroticism, [low] agreeableness, [low] conscientiousness) that can account for a broad range of psychopathology and be directly targeted in treatment. The overarching goal of the proposed study is to provide initial evidence that targeting this limited number of higher-order, personality-based dimensions represents a more potent, parsimonious, and personalized approach to mental healthcare. The goal of the R61 phase is to demonstrate target engagement by determining whether discrete therapy modules each designed to directly address one higher-order personality dimension engage their intended personality targets using multi-modal assessments of clinician-rated, self-report, and behavioral indicators. A single-case experiment to test engagement of each higher-order target (n = 10 in each sub-study) will be conducted. Participants will complete (1) an assessment-only baseline period to establish stability in the targeted personality dimension without treatment, (2) a 6-session intervention phase targeting the personality mechanism in which they demonstrated an elevation, and (3) a 4-week assessment-only follow-up. The proposed R33 project will be conducted if at least one personality-focused therapy module leads to improvement in its corresponding higher-order personality dimension (i.e., go/no go criteria). The goal of the R33 phase is to demonstrate target validation by determining whether improvement in higher-order personality targets leads to improvement in downstream clinical endpoints (i.e., DSM-5 disorder symptoms). Participants (N = 204) will be randomized to receive the personality-based treatment modules (6-18 sessions) corresponding to their clinically significant elevations, or to a waitlist condition. We will recruit participants with borderline personality disorder in both study phases as this disorder is characterized by combinations of high neuroticism, low agreeableness, and low conscientiousness,6,28,58 and frequently co-occurs with a variety of DSM-5 disorders that are accounted for by different personality domains.
Effective start/end date5/15/244/30/26


  • National Institute of Mental Health: $870,793.00


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