# Data-Driven Models of Symptom Heterogeneity to Empower Transdiagnostic Multimodal Biomarker Discovery in Mood Disorders

> **NIH NIH R00** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $220,389

## Abstract

PROJECT SUMMARY/ABSTRACT
My goal is to pursue an independent career in computational psychiatry by leveraging cutting-edge neuroimaging
and data-driven analysis approaches to advance precision medicine in mental health. To build on my strong
neuroimaging and computational background, the training component of this award emphasizes coursework and
mentorship in the clinical and behavioral aspects of psychopathology. I will also receive mentorship to advance
my theoretical and applied understanding of deep learning in this burgeoning field. The overarching research
goal in this proposal is to develop computational strategies that account for the heterogeneity of mood disorders
to improve the identification of treatment-response biomarkers. Response to pharmaceutical and behavioral
antidepressant treatments is low, likely due to the symptomatic and etiological heterogeneity of depression
whereby certain treatments may confer differential benefits for patients having particular symptom constellations.
In the K99 phase, I will seek to improve prediction of individual antidepressant response using electroconvulsive
therapy (ECT), which elicits robust and rapid antidepressant effects, as the treatment model. I will use MRI and
clinical data from patients undergoing ECT collected for the large the Global ECT-MRI Research Collaboration
(GEMRIC). In Aim 1, I will use exploratory factor analysis to characterize latent symptom dimensions of the
GEMRIC cohort before, during, and after ECT. The accuracy of predicting clinical outcomes along the recovered
symptom dimensions will be compared to traditional means of evaluating response using the total score of the
Hamilton Depression Rating Scale (HDRS). Pursuit of this aim will expand my understanding of clinical psychiatry
and lay foundational knowledge for the independent aims. Aim 2 will expand my deep learning and multimodal
neuroimaging skillsets as I develop novel deep learning architectures to fuse multimodal imaging features of
GEMRIC participants to further improve predictions of treatment response and cognitive impairment following
ECT. Rather than simply concatenating multimodal features together, deep network architectures will discover
latent feature representations. The R00 phase will be a logical progression of the skill sets I develop in the
mentored phase and expand on these lines of research. Aim 3 will draw from a collection of large-scale MRI
datasets from patients with more broadly defined mood disorders to identify multimodal imaging markers
associated with transdiagnostic symptom domains. Aim 4 uses treatment groups from aim 3, including patients
undergoing ketamine, sleep deprivation, cognitive behavioral therapy, and pharmaceuticals, to explore the extent
to which biomarkers of therapeutic response, defined along the transdiagnostic symptom dimensions identified
in Aim 3, are shared across treatment groups. I anticipate that discrete categorizations of mood disorders
artificially obscures...

## Key facts

- **NIH application ID:** 10832541
- **Project number:** 5R00MH119314-05
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Benjamin Seavey Cutler Wade
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $220,389
- **Award type:** 5
- **Project period:** 2019-09-06 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10832541

## Citation

> US National Institutes of Health, RePORTER application 10832541, Data-Driven Models of Symptom Heterogeneity to Empower Transdiagnostic Multimodal Biomarker Discovery in Mood Disorders (5R00MH119314-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10832541. Licensed CC0.

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