# Genetic, Imaging, and Cognition study of Positive Valence Systems in Psychotic Syndromes

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $636,235

## Abstract

Project Summary
The Research Domains Criteria (RDoC) initiative was developed by the NIMH to address growing concern
about the validity of the Diagnostic and Statistical Manual of Mental Disorders (DSM) and its potential to limit
research on mental illness. The overarching aim of RDoC to identify dimensions of brain structure and function
that will possess greater biological validity than our current taxonomy holds great promise for rational diagnosis
and treatment of mental illness. The proposed study aims to examine one of the core components of RDoC
that is focused on reward circuits and behavior, namely the Positive Valence Systems domain (PVS). The
PVS has been linked to diverse psychiatric disorders including schizophrenia, bipolar disorder and major
depressive disorder. There is consensus that schizophrenia and bipolar disorder share substantial genetic
risk and multiple overlapping phenotypic variations at the levels of corticostriatal brain circuits, cognitive
functions, and behavior. Yet it remains unknown precisely which dimensions are shared, which may diverge
between syndromes, and how the associated phenotypes relate to shared and non-shared genetic risk. The
proposed research will examine the RDoC PVS domains in two large genetically informative cohorts
comprising more than 5,000 individuals already ascertained in the Netherlands. Participants include 1,000
schizophrenia patients, 1,750 subjects with bipolar disorder, more than 1,000 first-degree relatives and almost
1,500 healthy comparison subjects. Extensive clinical and neurocognitive data is already available, which will
contribute significantly to our understanding of basic brain circuitry that controls behavior in health and disease.
Available genome-wide genotype and whole genome sequencing data provide a unique opportunity to
examine the heritability of the PVS measures and its relationship with the etiology of psychiatric disorder.
We will collect multi-level data pertaining to each of the four primary PVS component processes identified by
the RDoC Workshop focused on Reward Seeking and Consummatory Behavior (Approach Motivation) through
online assessments of these cognitive constructs. These will be further validated by in-laboratory measures
using functional MRI in a subset of participants (n=500). Analyses will focus on the ventral striatal (VS) and
ventromedial prefrontal cortex (vmPFC) responses to anticipation and receipt of reward. We will derive
response profiles from the four PVS cognitive tests that possess greatest concurrent validity with respect to
individual differences in neural circuit function.
Results of this study will provide important new data about the relations of the PVS component processes
proposed in RDoC to the primary neural circuits, and enable the results in our genetically informative samples
to be evaluated in the context of research on a broad range of mental disorders and healthy individuals.

## Key facts

- **NIH application ID:** 10248440
- **Project number:** 5R01MH114152-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** ROBERT M BILDER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $636,235
- **Award type:** 5
- **Project period:** 2018-09-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10248440

## Citation

> US National Institutes of Health, RePORTER application 10248440, Genetic, Imaging, and Cognition study of Positive Valence Systems in Psychotic Syndromes (5R01MH114152-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10248440. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*