Evidence map›Paper›PMID 40226746›Full record

SynthesisDepression and anxiety2024

The Dark and Gloomy Brain: Grey Matter Volume Alterations in Major Depressive Disorder-Fine-Grained Meta-Analyses.

Zaira Romeo, Margherita Biondi, Leif Oltedal, Chiara Spironelli

Abstract readMeta-Analysis
In one paragraph

Synthesis in Depression and anxiety, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Genome-Wide by Lifetime Environment Interaction Studies of Brain Imaging Phenotypes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  3. Neural Circuit Taxonomy and Precision Psychiatry in Major Depression.Advances in experimental medicine and biology · 2026
    Review
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Zaira RomeoDepartment of General Psychology, University of Padova, 35131 Padova, Italy.ORCID 0000-0002-0144-5840
Margherita BiondiDepartment of General Psychology, University of Padova, 35131 Padova, Italy.ORCID 0009-0008-4972-847X
Leif OltedalDepartment of Clinical Medicine, University of Bergen, 5020 Bergen, Norway.ORCID 0000-0003-3316-7950
Chiara SpironelliDepartment of General Psychology, University of Padova, 35131 Padova, Italy.ORCID 0000-0002-8547-2431

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: While the brain correlates of major depressive disorder (MDD) have been extensively studied, there is no consensus conclusion so far. Various meta-analyses tried to determine the most consistent findings, but the results are often discordant for grey matter volume (GMV) atrophy and hypertrophy. Applying rigorous and stringent inclusion criteria and controlling for confounding factors, such as the presence of anxiety comorbidity, we carried out two novel meta-analyses on the existing literature to unveil MDD signatures. Methods: A systematic literature search was performed up to January 2023. Seventy-three studies on MDD patients reporting GMV abnormalities were included in the first meta-analysis, for a total of 6167 patients and 6237 healthy controls (HC). To test the effects of anxiety comorbidity, we conducted a second meta-analysis, by adding to the original pure MDD sample a new cohort of MDD patients with comorbid anxiety disorders (308 patients and 342 HC). An activation likelihood estimation (ALE) analysis and a coordinate-based mapping approach separate for atrophy and hypertrophy were used to identify common brain structural alterations among patients. Results: The pure MDD sample exhibited atrophy in the left insula, as well as hypertrophy in the bilateral amygdala and parahippocampal gyri. When we added patients with comorbid anxiety to the original sample, bilateral insula atrophy emerged, whereas the hypertrophy results were not replicated. Conclusions: Our findings revealed important structural alterations in pure MDD patients, particularly in the insula and amygdala, which play key roles in sensory input integration and in emotional processing, respectively. Additionally, the amygdala and parahippocampal gyrus hypertrophy may be related to MDD functional overactivation to emotional stimuli, rumination, and overactive self-referential thinking. Conversely, the presence of anxiety comorbidity revealed separate effects which were not seen in the pure MDD sample, underscoring the importance of strict inclusion criteria for investigations of disorder-specific effects.

Indexed as

Anxiety DisordersBrainGray MatterMajor Depressive DisorderAmygdalaAtrophyComorbidityHumansHypertrophyMagnetic Resonance Imaging

Identifiers

PMID40226746
PMCPMC11919126

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.