Association of Disease Severity with Longitudinal Changes in Gray Matter Volume in Individuals Diagnosed with Major Depressive Disorder

By
Anna Kraus
Janik Goltermann
Tiana Borgers
Katharina Dohm
Dominik Grotegerd
Elisabeth Schrammen
Kira Flinkenflügel
Verena Enneking
Elisabeth J. Leehr
Joscha Böhnlein
Nils Winter
Alea Bexten
Tim Hahn
Jochen Bauer
Marius Gruber
Jonathan Repple
Katharina Förster
Eva Mennigen
Nils Opel
Tilo Kircher
Susanne Meinert
Udo Dannlowski
September 14, 2026

Jama Network Open

Overview

This study investigates the longitudinal changes in gray matter volume (GMV) in patients with major depressive disorder (MDD) over a period of up to 10 years. It highlights the relationship between cumulative illness severity and GMV decline.

Background

Major depressive disorder (MDD) is associated with significant structural brain alterations, particularly in gray matter volume (GMV). Understanding the relationship between disease severity and GMV changes is essential.

Data Highlights

This study utilized neuroimaging and clinical assessments over multiple time points to evaluate GMV in key brain regions associated with MDD.

Key Findings

Patients with MDD exhibited a steeper longitudinal decline in GMV compared to healthy controls.
Greater cumulative illness severity was associated with a more pronounced decline in GMV among patients with MDD.
Longitudinal changes in GMV may reflect either progressive alterations or dynamic, state-dependent changes.
Previous studies have shown larger GMV decreases linked to failed remission and relapse in specific brain regions.
Methodological limitations in existing studies highlight the need for more comprehensive longitudinal research.

Clinical Implications

Understanding the relationship between cumulative illness severity and GMV changes can aid in identifying patients at risk for relapse.

Conclusion

The findings highlight the importance of longitudinal assessments in understanding the neurobiological underpinnings of MDD.

Association of Disease Severity with Longitudinal Changes in Gray Matter Volume in Individuals Diagnosed with Major Depressive Disorder