# Mapping heterogeneity of brain microstructural abnormalities in psychiatric disorders with normative modelling

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2024 · $562,757

## Abstract

PROJECT SUMMARY/ ABSTRACT
 The central premise of precision medicine is that an individual’s unique physiologic characteristics play
a significant role in disease vulnerability and response to specific therapies. To make progress towards
precision medicine in psychiatry it is imperative to move beyond group-based studies that disregard individual
variations as noise, and instead interpret individual variations in the context of the normal-range of biological
systems, which is consistent with the Research Domain Criteria [RDoC] paradigm.
 In response to the Notice of Special Interest (NOSI) regarding the use of Human Connectome Data for
Secondary Analysis we propose to use normative modeling (‘brain growth charting’) techniques to generate a
comprehensive reference atlas for brain microstructure across the lifespan that contains age and sex based
normative information for individual brain regions using publicly available connectome data (>50,000 individual
datasets, age 10-100 years). We chose to target brain microstructure because postmortem and neuroimaging
studies have implicated microstructural involvement in virtually all major psychiatric disorders. We will also
create a web-based ecosystem that contains the relevant workflow components, including an option to
calibrate models to new datasets. In addition to publishing final models and code as Jupyter notebooks, we will
design a graphical user interface to reduce barriers for neuroscientists with limited experience in command line
coding and to maximize the impact of our work. Taken together, this approach will provide a problem-agnostic,
quantitative framework for characterizing variations at the individual level and give us a paradigm-shifting
opportunity to advance clinical translation, where information of an individual patient’s brain microstructure can
be leveraged to forecast the probability of a psychiatric condition, clinical outcomes, or response to treatment.
 We will showcase the value of this approach for psychiatric applications by determining the extent and
clinical relevance of individual microstructure deviations in early psychosis patients. We chose this patient
population because it is genetically and phenotypically heterogeneous, confounds of disease chronicity and
antipsychotic medication exposure are limited, and because we have found that subtle microstructural
abnormalities are already present at illness onset and associated with clinical and outcome variables. Using
publicly available connectome data, we first will assess the extent of individual microstructure variations and
assess heterogeneity in microstructural deviations from the norm in this patient population. We will then test
the relationships between individual microstructure variations and key clinical variables, and determine if
individual microstructural variations can be used to identify clinical subtypes. This constitutes a pivotal step
towards precision psychiatry, where patients are conceptualized ba...

## Key facts

- **NIH application ID:** 10918155
- **Project number:** 5R01MH130362-02
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Nina Vanessa Kraguljac
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $562,757
- **Award type:** 5
- **Project period:** 2023-09-01 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10918155

## Citation

> US National Institutes of Health, RePORTER application 10918155, Mapping heterogeneity of brain microstructural abnormalities in psychiatric disorders with normative modelling (5R01MH130362-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10918155. Licensed CC0.

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