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

> **NIH NIH R61** · UNIVERSITY OF KENTUCKY · 2024 · $870,793

## Abstract

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.

## Key facts

- **NIH application ID:** 10867107
- **Project number:** 1R61MH133665-01A1
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Shannon E Sauer-Zavala
- **Activity code:** R61 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $870,793
- **Award type:** 1
- **Project period:** 2024-05-15 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10867107

## Citation

> US National Institutes of Health, RePORTER application 10867107, Engaging Higher-Order Mechanisms of Psychopathology: A Parsimonious Approach to Precision Medicine (1R61MH133665-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10867107. Licensed CC0.

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