2026 ECNP Congress

PS03-3114

Why does It feel so intense? A novel approach to neurofunctional alterations in MDD

Robin Kamrla — K. Schöniger, K. Antonia, R. Ronny · Martin-Luther-Universität Halle, Biological and Clinical Psychology, Halle, Germany

2026 ECNP Congress

Introduction

The prevalence of affective disorders such as major depressive disorder (MDD) remains high across all age cohorts worldwide and continues to rise. However, previous neuroimaging research on emotional processing in MDD has yielded heterogeneous findings, often characterized by small effect sizes when comparing fMRI responses between individuals with MDD and healthy controls (HC) to a priori defined emotional stimuli. This inconsistency may partly reflect a missing link between measures of neurofunctional alterations in MDD and the disorder’s psychopathology. In this work, we are moving beyond the exclusive use of emotional images – typically eliciting averaged neural responses – and instead incorporating participants’ subjective evaluations.

Methods

We pursued a novel individual-level modeling approach to functional MRI data. N=275 participants — including healthy controls (nHC=224) and patients with depression (nMDD=51) — completed an emotional processing paradigm. The fMRI measures included trial-wise neural activation in view of pictures with negative and neutral emotional valence and corresponding trial-level subjective emotional ratings of negativity. Blood-oxygen-level dependent responses were modeled for each individual using subjective emotional ratings as parametric regressors. Brain-wide activation differences between HC and MDD on negative stimuli, neutral stimuli and averaged over negative and neutral stimuli were analyzed by means of a t-test’s and threshold free cluster enhancement (TFCE) using 5000 permutations at a family-wise error correction threshold of pFWE<.05.

Results

The analysis of stimuli with strong negative valence revealed increased brain activation with increasing negativity rating in MDD compared to HC. Significant differences were found in widespread brain areas including the cerebellum and adjacent regions in the posterior cerebrum (k=4755 voxels, t(271)=6.31, pFWE-TFCE<.001, d=1.13), parietal regions (k=2167 voxels, t(271)=6.18, pFWE-TFCE<.001, d=0.98), frontal regions (k=496 voxels, t(271)=5.30, pFWE‑TFCE=.001, d=0.84) as well as the left (k=219 voxels, t(271)=5.21, pFWE‑TFCE=.002, d=0.85) and right basal ganglia (k=250 voxels, t(271)=5.13, pFWE-TFCE=.002, d=0.83), and limbic regions (k=77 voxels, t(271)=5.12, pFWE‑TFCE=.002, d=0.88). The analysis averaging over neutral and negative stimuli yielded significant increased brain activation with increasing negativity rating in MDD compared to HC in the right inferior and middle temporal lobule (k=50 voxels, t(271)=5.00, pFWE-TFCE=.007, d=0.83) and in the right supramarginal lobule (k=57 voxels, t(271)=4.51, pFWE-TFCE=.023, d=0.73).

Discussion

This study aimed to bridge the gap between established knowledge on the psychopathology of depressive disorders and their neural underpinnings by combining a subjective evaluation task with the presentation of emotional stimuli. This captured the variation in neural activation due to the differing intensity of emotional stimuli between the individual participants, allowing for more robust group-level comparison. The novel integrative analysis framework allowed for the assessment of altered neural emotional responsiveness in MDD, revealing — for the first time — robust effects and large effect sizes. Importantly, the findings highlight the advantages of using subjective evaluations over a priori assigned emotional values, while also providing new insights into the neural basis of altered emotional responsiveness in MDD.

References

No references