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Mapping subtype-specific disease epicenters and brain aging characteristics in major depressive disorder through normative model-driven analysis of brain structural alterations
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Mapping subtype-specific disease epicenters and brain aging characteristics in major depressive disorder through normative model-driven analysis of brain structural alterations
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Journal Article
Mapping subtype-specific disease epicenters and brain aging characteristics in major depressive disorder through normative model-driven analysis of brain structural alterations
2025
Overview
•Based on GMV deviations, we identified two distinct subtypes of structural changes in MDD: one characterized by GMV reduction and the other by GMV increase.•Our study found that the GMV increase subtype does not exhibit signs of accelerated brain aging.•We discovered that different structural subtypes of MDD share common epicenters within the DMN, while also possessing their own specific epicenters.•We revealed that the heterogeneity of structural changes in MDD involves distinct microscopic molecular characteristics.
Major depressive disorder (MDD), a prevalent mental health condition, manifests intricate alterations in brain structure that evolve gradually over time and across various brain regions. Despite significant research efforts, two fundamental questions remain unsettled: the precise brain origins of MDD and whether MDD contributes to accelerates brain aging. To this end, we conducted a comprehensive investigation leveraging data from 830 MDD patients and 853 matched healthy controls (HC). Normative models, established on HC gray matter volume (GMV) data, were utilized to quantify individual deviations in GMV among MDD patients. Employing k-means clustering to these deviation profiles, we successfully discerned two clinically distinct subtypes. Subtype 1 is characterized by GMV atrophy, coupled with indications of accelerated brain aging processes. In contrast, subtype 2 exhibits increased GMV without significant acceleration of aging phenomena. Intriguingly, both subtypes converge on the default mode network as a common disease epicenter, highlighting a shared neurophysiological underpinning. However, subtype-specific epicenters diverge, with subtype 1 featuring unique foci primarily in the hippocampus and amygdala, whereas subtype 2 distinguishes itself with epicenters primarily located in the accumbens. This nuanced examination of subtype-specific brain alterations, incorporating their intricate spatiotemporal dynamics, provides profound insights into the heterogeneity and complexity inherent in MDD.
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Publisher
Elsevier Inc,Elsevier Limited,Elsevier
Subject
/ Age
/ Aged
/ Aging
/ Amygdala
/ Atrophy
/ Disease
/ Dopamine
/ Female
/ Gene
/ Gray Matter - diagnostic imaging
/ Humans
/ Magnetic Resonance Imaging - methods
/ Major Depressive Disorder - classification
/ Major Depressive Disorder - diagnostic imaging
/ Major Depressive Disorder - pathology
/ Male
/ Patients
/ Radiology/Diagnostic Imaging
