# Elucidating Olfactory Mechanisms of PTSD Vulnerability and Trauma Resilience

> **NIH NIH R21** · HOWARD UNIVERSITY · 2020 · $189,069

## Abstract

ABSTRACT
Faced with severe psychological trauma, some people develop post-traumatic stress disorder (PTSD), but
most people don't. Current understanding of the biological mechanisms underlying resilience from, and
vulnerability to PTSD remains limited. Neuroscience suggests that the olfactory bulb (OB), a key structure in
odor processing, may also be involved in mechanisms of traumatic stress. In animals, chronic stress reduces
OB size; while OB ablation results in stress-enhanced startle reflex, amygdala reactivity, structural
reorganization of limbic structures and autonomic dysregulation. Furthermore, OB lesion causes
hyperexcitability of medial amygdaloid neurons through NMDA-based mechanisms. However, OB
morphometry has not been adequately studied in the development of stress disorders in humans. Our recently
published study of adults who suffered sexual and/or physical abuse during childhood (N=16), revealed that
OB volumes of trauma-exposed PTSD subjects (T1P1) were substantially reduced compared to OB volumes of
trauma-exposed subjects who did not develop PTSD (T1P0). Additionally, while OB volumes of T1P0 and non-
trauma exposed healthy control (HC) groups were statistically similar, those of T1P1 were significantly reduced
compared to HC. Furthermore, preliminary findings from our ongoing longitudinal study of T1P1 and T1P0
adults with childhood sexual trauma show that reduced OB size is associated with physiological indices of
amygdala disinhibition 6 months later. Given recent strong preclinical evidence of bidirectional relationships in
molecular events between olfactory neurons (ON) and OB, and our discovery that immunohistochemical
markers of ON survival in patient-derived olfactory tissues are predictive of their OB volumes, we compared
expression patterns in ON of T1P1 and T1P0 and found differentially elevated levels of Growth arrest specific 5
(GAS5) in olfactory cells derived noninvasively from T1P0. GAS5 is a long noncoding RNA (lncRNA) that
mimics corticotropin response elements in the promoter regions of genes that respond to glucocorticoids. By
binding to these regions, GAS5 competitively blocks the transcriptional effects of glucocorticoids on these
genes and protect the tissues from atrophy. Although a mechanistic hypothesis of GAS5 is compelling from our
preliminary data, the National Institute of Mental Health is moving from funding candidate gene approaches to
unbiased omic approaches. As a result, we propose a 2-year prospective R21 study on a larger sample of non-
smoking subjects exposed to childhood sexual abuse (N=60, 60% females) and 20 healthy controls, to: (1)
validate differences in OB and other olfactory regions in T1P0 (N=30) and T1P1 (N=30), matched on duration
of assault and years since last assault; (2) quantify the relationship between OB morphometry and dimensional
measures of stress and resilience, including electrodermal responses to aversive visual stimuli on all subjects
at baseline (2.1) and the m...

## Key facts

- **NIH application ID:** 9924690
- **Project number:** 5R21MH117987-02
- **Recipient organization:** HOWARD UNIVERSITY
- **Principal Investigator:** Evaristus A Nwulia
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $189,069
- **Award type:** 5
- **Project period:** 2019-05-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9924690

## Citation

> US National Institutes of Health, RePORTER application 9924690, Elucidating Olfactory Mechanisms of PTSD Vulnerability and Trauma Resilience (5R21MH117987-02). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/9924690. Licensed CC0.

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