Mehta · Brain, behavior, and immunity 2018 · Cross-sectional observational study · n=48

Inflammation negatively correlates with amygdala-ventromedial prefrontal functional connectivity in association with anxiety in patients with depression: Preliminary results.

Cited 118 times in the scientific literature.

Level 4 - case-series / case-control

Cross-sectional observational biomarker and neuroimaging study

PubMed 30076980 · doi:10.1016/j.bbi.2018.07.026 · record verified 2026-08-29

What was done

Resting-state functional MRI (rfMRI) and plasma C-reactive protein (CRP) measurements were obtained in 48 medically stable, currently unmedicated outpatients with a primary diagnosis of major depressive disorder (MDD). Whole-brain voxel-wise functional connectivity analyses of the right and left amygdala were performed as a function of CRP levels, and identified connectivity metrics were examined against anxiety symptom severity.

What was found

Increased plasma CRP predicted decreased resting-state functional connectivity between the right amygdala and left ventromedial prefrontal cortex (vmPFC) (corrected p < 0.05). Amygdala-vmPFC connectivity was negatively correlated with anxiety symptoms (r = -0.33, df = 46, p = 0.022). In exploratory subgroup analyses, this relationship between low amygdala-vmPFC connectivity and high anxiety remained significant only in patients with a secondary diagnosis of an anxiety disorder or PTSD (r = -0.54 to -0.87, p < 0.05).

Why it matters

The findings identify impaired amygdala-vmPFC functional connectivity as a potential neural pathway through which peripheral inflammation may drive anxiety symptoms in major depression, particularly in the context of comorbid trauma or anxiety.

Limits

The sample size was small (n = 48), limiting statistical power. The cross-sectional design cannot establish causality between peripheral inflammation, circuit connectivity, and anxiety symptoms. Findings in patients with secondary anxiety disorders or PTSD were exploratory.

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