# MRI markers of neuroinflammation in untreated patients with subclinical generalized anxiety disorder

**Authors:** Balázs Barkó, Oguz Kelemen, Szabolcs Kéri

PMC · DOI: 10.1007/s00702-025-03014-x · 2025-09-11

## TL;DR

This study finds evidence of neuroinflammation in the amygdala of untreated subclinical generalized anxiety disorder patients using MRI markers.

## Contribution

The study identifies elevated neuroinflammatory markers in the amygdala of sub-GAD patients, linking them to anxiety severity.

## Key findings

- Sub-GAD patients showed elevated inflammatory MRI markers in the amygdala compared to controls.
- DBSI-RF values in the amygdala correlated with anxiety severity but not depression scores.
- No significant changes were observed in the hippocampus or neocortex.

## Abstract

Generalized Anxiety Disorder (GAD) is characterized by excessive worry and physical symptoms of prolonged anxiety. Patients with subclinical GAD-states (sub-GAD) do not fulfill the diagnostic criteria of GAD, but they often show a disease burden similar to GAD, and the subclinical state may turn into a full syndrome. Neuroinflammation may contribute to changes in brain structures in sub-GAD, but direct evidence remains lacking. We investigated 73 newly recruited sub-GAD patients who had never received pharmacological or psychological treatment and 64 matched non-clinical individuals. We utilized magnetic resonance imaging (MRI) to assess putative neuroinflammatory markers (DBSI-RF, diffusion-based spectral imaging-based restricted fraction) in the hippocampus, amygdala, and neocortex. The patients completed the Hamilton Anxiety Rating Scale (HAM-A), the Generalized Anxiety Disorder 7-item scale (GAD-7), and the Beck Depression Inventory-II (BDI-II). Compared to controls, sub-GAD individuals had significantly elevated inflammatory MRI markers in the amygdala but not in the hippocampus and neocortex. The DBSI-RF values correlated with the severity of anxiety (HAM-A and GAD-7 scores), but not with BDI-II. These findings suggest that neuroinflammation in the amygdala may play a critical role in the development of anxiety in sub-GAD.

## Linked entities

- **Diseases:** Generalized Anxiety Disorder (MONDO:0001942)

## Full-text entities

- **Diseases:** GAD (MESH:C000726808), inflammatory (MESH:D007249), Neuroinflammation (MESH:D000090862), Anxiety (MESH:D001007), Depression (MESH:D003866)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12999678/full.md

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Source: https://tomesphere.com/paper/PMC12999678