Profound and reproducible patterns of reduced regional gray matter characterize major depressive disorder

Sarah C Hellewell; Thomas Welton; Jerome J Maller; Matthew Lyon; Mayuresh S Korgaonkar; Stephen H Koslow; Leanne M Williams; A John Rush; Evian Gordon; Stuart M Grieve

doi:10.1038/s41398-019-0512-8

Back

Profound and reproducible patterns of reduced regional gray matter characterize major depressive disorder

Journal article

Open access

Peer reviewed

Profound and reproducible patterns of reduced regional gray matter characterize major depressive disorder

Sarah C Hellewell, Thomas Welton, Jerome J Maller, Matthew Lyon, Mayuresh S Korgaonkar, Stephen H Koslow, Leanne M Williams, A John Rush, Evian Gordon and Stuart M Grieve

Translational psychiatry, Vol.9(1), pp.176-8

07/24/2019

DOI: 10.1038/s41398-019-0512-8

PMCID: PMC6656728

PMID: 31341158

Files and links (1)

url

https://doi.org/10.1038/s41398-019-0512-8View

Published (Version of record) Open Access

Abstract

Reduced gray matter (GM) volume may represent a hallmark of major depressive disorder (MDD) neuropathology, typified by wide-ranging distribution of structural alteration. In the study, we aimed to replicate and extend our previous finding of profound and widespread GM loss in MDD, and evaluate the diagnostic accuracy of a structural biomarker derived from GM volume in an interconnected pattern across the brain. In a sub-study of the International Study to Predict Optimized Treatment in Depression (iSPOT-D), two cohorts of clinically defined MDD participants "Test" (n = 98) and "Replication" (n = 131) were assessed alongside healthy controls (n = 66). Using 3T MRI T1-weighted volumes, GM volume differences were evaluated using voxel-based morphometry. Sensitivity, specificity, and area under the receiver operating characteristic curve were used to evaluate an MDD diagnostic biomarker based on a precise spatial pattern of GM loss constructed using principal component analysis. We demonstrated a highly conserved symmetric widespread pattern of reduced GM volume in MDD, replicating our previous findings. Three bilateral dominant clusters were observed: Cluster 1: midline/cingulate (GM reduction: Test: 6.4%, Replication: 5.3%), Cluster 2: medial temporal lobe (GM reduction: Test: 8.2%, Replication: 11.9%), Cluster 3: prefrontal cortex (GM reduction: Test: 12.1%, Replication: 23.2%). We developed a biomarker reflecting the global pattern of GM reduction, achieving good diagnostic classification performance (AUC: Test = 0.75, Replication = 0.84). This study establishes that a highly specific pattern of reduced GM volume is a feature of MDD, suggestive of a structural basis for this disease. We introduce and validate a novel diagnostic biomarker based on this pattern.

Adult

Biomarkers

Cerebral Cortex - diagnostic imaging

Cerebral Cortex - pathology

Cohort Studies

Depressive Disorder, Major - classification

Depressive Disorder, Major - diagnostic imaging

Depressive Disorder, Major - pathology

Female

Gray Matter - diagnostic imaging

Gray Matter - pathology

Humans

Magnetic Resonance Imaging

Male

Middle Aged

Sensitivity and Specificity

Young Adult

Details

Title: Subtitle: Profound and reproducible patterns of reduced regional gray matter characterize major depressive disorder
Creators: Sarah C Hellewell - The University of Sydney
Thomas Welton - The University of Sydney
Jerome J Maller - The University of Sydney
Matthew Lyon - The University of Sydney
Mayuresh S Korgaonkar - Westmead Institute for Medical Research
Stephen H Koslow - University of Miami
Leanne M Williams - VA Palo Alto Health Care System
A John Rush - National University of Singapore
Evian Gordon - The Heart Research Institute
Stuart M Grieve - Royal Prince Alfred Hospital
Resource Type: Journal article
Publication Details: Translational psychiatry, Vol.9(1), pp.176-8
DOI: 10.1038/s41398-019-0512-8
PMID: 31341158
PMCID: PMC6656728
NLM abbreviation: Transl Psychiatry
ISSN: 2158-3188
eISSN: 2158-3188
Language: English
Date published: 07/24/2019
Academic Unit: Radiology
Record Identifier: 9984848426202771

Metrics

6 Record Views

See more details