# Individual Multimodal Pathway Statistics for Predicting Treatment Response in Late-life Depression

> **NIH NIH K01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $176,521

## Abstract

Modest response rates to first-line antidepressant treatment for late-life depression (LLD) expose individuals to
prolonged depressive symptoms that worsen their prognosis and associated health risks. Biomarkers of
treatment response can alleviate this burden by identifying individuals most likely to benefit from
antidepressant treatment. MRI measures of brain structure and function are a promising tool to identify such
biomarkers, though the performance required for clinical translation has remained elusive. The goal of this
proposal is to integrate complementary network measures from structural and functional MRI with
clinical measures to generate biologically relevant features that can improve prediction of treatment
outcome in LLD. The anticipated impact of this research will provide improved personalization of LLD
treatment (NIMH Strategic Objective 3.2), while elucidating the neural circuitry indicative of treatment outcome
(Objective 1.3). To achieve this goal, structural, resting state, and diffusion-weighted MRI will be collected from
75 participants with LLD before commencing an algorithmic antidepressant treatment protocol. The role of
resting state functional connectivity as a mediator of the relationship between structural connectivity and
clinical measures (baseline depression severity and change in depression severity over treatment) will be
investigated within key neural circuitry at the group level. Individual Multimodal Pathway Statistics (IMPathS)
will be derived to quantify the personalized importance of functional connectivity to the relationship between
structural connectivity and depression severity for prediction of treatment outcome at the individual level. Utility
of IMPathS will be assessed by their ability to improve performance beyond unimodal MRI and clinical
predictors. Dr. Gerlach has a PhD in nuclear engineering and radiological sciences and is completing a
transition from computational physics to computational neuroscience. He will require additional training in 1)
the neurobiology, clinical manifestations, and treatment of LLD, 2) diffusion-weighted imaging processing and
analysis, 3) advanced statistical training for development and testing of IMPathS, 4) human subjects, study
design, and data collection. Completion of the training and research plan in this career development award will
enable Dr. Gerlach to progress to an independent investigator focused on investigating the neurobiology of late
life anxiety and mood disorders through improved integration of multimodal neuroimaging measures. Dr.
Gerlach will execute this training and research with the full support of the Department of Psychiatry at the
University of Pittsburgh, which is a highly collaborative environment focused on the development of early
career scientists.

## Key facts

- **NIH application ID:** 10898730
- **Project number:** 5K01MH133913-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Andrew Robert Gerlach
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $176,521
- **Award type:** 5
- **Project period:** 2023-08-03 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10898730

## Citation

> US National Institutes of Health, RePORTER application 10898730, Individual Multimodal Pathway Statistics for Predicting Treatment Response in Late-life Depression (5K01MH133913-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10898730. Licensed CC0.

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