Disentangling the anatomical, functional and clinical heterogeneity of major depression, using machine learning methods

Ended Project Grant Awarded Last action

Award ID
R01MH134236
Recipient
Awarding agency
Obligated
$2,275,576

Award facts

Assistance listing
93.242 Mental Health Research Grants
Completion date
Place of performance
Pennsylvania, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Neuropsychiatric disorders are characterized by distinct as well as shared clinical features that present in heterogeneous symptom profiles. Delineating the neurobiological etiology of clinical symptoms has been a key overarching aim of over 20 years of neuropsychiatric research. From the earliest studies, neuroimaging research has identified abnormalities in regional brain structure and function. However, we know that there is significant heterogeneity in brain structure and function in neuropsychiatric disorders. Imaging analytic and machine learning methods developed by our group provide the analytic approaches needed to quantify heterogeneity in neuropsychiatric disorders. Herein we leverage these methods, along with a broad international collaboration which provides a unique resource of large highly phenotyped datasets, in order to quantify heterogeneity in major depressive disorder (MDD). In the proposed project, we focus on neuroanatomy and neurofunctional connectivity in MDD. We aim to identify imaging signatures and subtypes in MDD by applying state-of-the-art harmonization, pattern analysis and machine learning methods to structural and resting state functional MRI. The analytic methods allow US to quantify the neuroanatomical and neurofunctional connectivity patterns that comprise MDD to provide powerful predictive markers at the individual level. Our goal is to arrive at a new neuroanatomical-neurofunctional (NA-NF) dimensional coordinate system in MDD (MDD coordinates), whereby each dimension reflects a different pattern of brain alterations, hence capturing the underlying NA-NF heterogeneity in quantifiable, replicable, and neurobiologically-based metrics. We will leverage data from our pooled cohorts consists of 4,973 adults with first episode and recurrent MDD, in a current depressive episode, that is not treatment resistant, all medication-free, and respective healthy controls. Assembling these large and powerful datasets will allow US to test our first hypothesis, namely that neuroanatomical and neurofunctional phenotypes will display high heterogeneity, which will allow US to define NA-NF dimensions of pathology. We then test the second hypothesis, namely that this heterogeneity will relate to disease-related phenotypes in MDD and different patterns of clinical outcome. Our specific aims will 1) refine and apply advanced harmonization methods in order to constructively pool and integrate this unique resource; 2) dissect the heterogeneity of the neuroanatomy and function in MDD, thereby deriving a neuroimaging- based coordinate system; 3) relate these imaging dimensions with clinical phenotypic measures, including response to treatment.

Transactions

Action Obligated Date
Amendment $0
Amendment $0
Amendment $0
Amendment $732,970
Amendment $771,303
Original award $771,303

Subawards

Subrecipient Amount Awarded
University Of East London Cynthia Fu, MD, PhD, will oversee all aspects in Aim 1 (Section C.3.3 Harmonization of clinical measure), Aim 2b and Aim 3b. Dr. Fu brings essential clinical… $95,206
University Of East London $95,206

Quick answers

Who received award R01MH134236?

R01MH134236 was awarded to The Trustees Of The University Of Pennsylvania by National Institute of Mental Health (National Institutes of Health) on August 1, 2023.

How much is award R01MH134236 worth?

$2,275,576 has been obligated on R01MH134236.

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