# Trauma and Genomics Modulate Brain Structure across Common Psychiatric Disorders

> **NIH NIH R01** · DUKE UNIVERSITY · 2020 · $459,250

## Abstract

ABSTRACT
Exposure to trauma and abuse during childhood, a critical neurodevelopmental period, is a major risk factor
for adult psychopathology. However, not all children exposed to childhood trauma will develop adult
psychopathology. Variability in the risk for trauma-related pathology is expected to arise in part from genetic
susceptibility. Several genes have recently been identified that interact with childhood trauma to increase rates
of anxiety and mood disorders in adulthood. This risk can be more easily detected by examining
endophenotypes such as brain measures obtained from MRI because of a simpler underlying genetic
architecture with fewer individual genes or pathways than the multiple factors driving overall risk for
psychopathology. Understanding the molecular-genetic contributors to brain structure that conspire with
early-life environment (psychological trauma) and lead to adult psychopathology, will require large-scale
collaborative efforts which harness big-data methodologies. Our goal is to conduct a GWAS of relevant
structural brain measures in individuals exposed to childhood trauma, with the long-term goal of identifying
genetic modulators of brain structure that are informative for early prediction and treatment for a range of
psychiatric disorders where childhood trauma is a major risk factor. We hypothesize that (1) childhood trauma
will interact with specific genetic markers to produce structural brain alterations and adult psychopathology,
(2) that unique genetic variants, in the context of genetic vulnerability to childhood trauma, will influence the
onset of specific disorders (e.g. depression vs PTSD), as well as (3) the presentation of specific symptom
constructs (e.g. sustained threat) across disorders. Finding disease-associated genetic variation that point to
molecular mechanisms of pathogenesis has proven challenging due to the polygenicity of clinical phenotypes.
Leveraging neuroimaging phenotypes may offer a more direct path than clinical phenotypes in identifying
these elusive genetic markers and relevant neurobiological pathways. Ultimately, the promise of finding genetic
contributors of any psychiatric disorder is in identifying the presence of new biologic pathways for which
targeted interventions may be devised and deployed.

## Key facts

- **NIH application ID:** 9974588
- **Project number:** 5R01MH111671-04
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** NEGAR FANI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $459,250
- **Award type:** 5
- **Project period:** 2017-09-06 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9974588

## Citation

> US National Institutes of Health, RePORTER application 9974588, Trauma and Genomics Modulate Brain Structure across Common Psychiatric Disorders (5R01MH111671-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9974588. Licensed CC0.

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