# Sex-Specific Functional Connectivity Changes in Major Depressive Disorder

> **NIH NIH F30** · WEILL MEDICAL COLL OF CORNELL UNIV · 2022 · $49,584

## Abstract

PROJECT SUMMARY
 The goal of this project is to develop sex-specific resting state fMRI biomarkers for major depressive
disorder (MDD) and to determine their underlying genetic correlates. Our primary aim is to determine the
locations and the degree of sex-specific functional connectivity differences associated with MDD patients as
compared to healthy subjects, and to test whether those sex-specific connectivity differences define sex-specific
subtypes of MDD. The benefit of achieving these goals will be twofold: (1) in the clinic, achieving these goals will
allow for more accurate diagnostic and treatment-response predictive algorithms for MDD, to reduce time to
remission in MDD patients. (2) In the laboratory, our work will guide discovery of novel sex-specific circuit
mechanisms and treatments for MDD. Our second aim is to determine if sex-specific MDD effects on connectivity
can be predicted by regional gene expression in the brain. Investigating the relationship between brain gene
expression and MDD effects on functional connectivity would implicate novel genes in the circuit mechanism of
MDD and identify genes that interact with sex in driving MDD symptomatology. To achieve these aims, we will
use parametric and non-parametric statistical testing to define sex-specific functional connectivity differences
between depressed and healthy men, and between depressed and healthy women. Secondary analyses will test
whether sex-specific classifiers for differentiating MDD subjects and healthy controls (“diagnostic biomarkers”)
outperform classifiers trained on all subjects independent of sex. To identify genetic correlates of sex-specific
MDD effects on functional connectivity, we will use the multivariate technique of partial least squares regression
to locate linear combinations of genes which can predict MDD-related connectivity differences in males and in
females. Finally, to identify sex-specific subtypes of MDD, we will use a combination of regularized canonical
correlation analysis and hierarchical clustering in a validated method for subtype discovery previously published
in Dr. Conor Liston’s lab. This project will fill a substantial gap in our knowledge of sex differences in MDD
functional connectivity and the underlying genetic correlates of those differences. This project will also involve
the execution of a concrete training plan to allow me to develop concrete technical skills in fMRI analysis and
machine learning techniques, conceptual skill in hypothesis testing, data interpretation, and scientific
communication, and clinical competency as a licensed physician, all under the guidance and mentorship of the
project’s sponsor Dr. Liston and co-sponsor Dr. Francis Lee, who are both accomplished physician-scientists.

## Key facts

- **NIH application ID:** 10427185
- **Project number:** 5F30MH124317-02
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Aleksandr Talishinsky
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $49,584
- **Award type:** 5
- **Project period:** 2021-06-04 → 2023-06-03

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10427185

## Citation

> US National Institutes of Health, RePORTER application 10427185, Sex-Specific Functional Connectivity Changes in Major Depressive Disorder (5F30MH124317-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10427185. Licensed CC0.

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