2026 ECNP Congress

PS04-4106

Exploring the impact of quality of life on brain structure and resting-state connectivity in depression

Alessia Giovanelli — M. Chiara, M. Paolini, S. Furno, V. Saredi, C. Colombo, R. Zanardi, S. Poletti, F. Benedetti · IRCCS San Raffaele Hospital, Division of Neuroscience- Psychiatry and Clinical Psychobiology Unit, Milan, Italy

2026 ECNP Congress

Background

Major Depressive Disorder (MDD) is a chronic, recurrent condition characterized by persistent low mood, anhedonia, cognitive impairment, and neurobiological changes that affect brain structure and function [1]. MDD affects 15-20% of people worldwide over their lifetime and is the leading cause of years lived with disability globally [2], [3]. Although antidepressants remain the first-line treatment, their efficacy varies substantially, with remission rates of only 30-50%, underscoring the need for individualized approaches [4].

Quality of life (QOL), as conceptualized by the World Health Organization, reflects an individual’s perceived well-being in the context of personal goals, expectations, and environmental conditions. It has been shown to influence the course of MDD and response to therapy [5]. This study investigates associations of QOL with gray matter volume and resting-state functional connectivity in MDD.

Methods

We enrolled 85 patients diagnosed with MDD according to DSM-5 criteria. These patients completed questionnaires on QOL and underwent 3-Tesla MRI scans, including T1-weighted images and resting-state fMRI sequences. QOL was evaluated using the WHO Quality of Life scale (WHOQOL-BREF), which captures individuals’ subjective perceptions of health and its influences overall (WHOQOL_tot) and within specific domains: physical, psychological, environmental, and social.

For Voxel-Based Morphometry (VBM) analyses, T1-weighted images were processed with the Computational Anatomy Toolbox (CAT12) within Statistical Parametric Mapping 12 (SPM12) using Matlab R2016b. The processing included segmentation into gray matter (GM), white matter, and cerebrospinal fluid, bias regularization, non-linear modulation, and normalization to MNI space. Images were smoothed using an 8-mm FWHM Gaussian filter, total intracranial volume (TIV) was calculated, and multiple regression analyses were performed in SPM12.

Resting-state (rs-FC) fMRI data were processed using the CONN toolbox in SPM12. The preprocessing steps followed the standard CONN pipeline: (i) realignment to correct for movement and distortion; (ii) slice timing correction; (iii) detection of outliers; (iv) normalization to MNI space and tissue segmentation; (v) spatial smoothing with an 8 mm Gaussian kernel; (vi) noise removal, accounting for motion and ‘scrubbed’ artifacts as covariates; (vii) linear detrending to eliminate drift and high-frequency noise.

Results

VBM analysis revealed a positive correlation between social QOL and GM volume in two clusters: Cluster 1 is located in the right Temporal Pole (k=1357, pFWE=0.009), and Cluster 2 in the right Middle Temporal Gyrus (k=1942, pFWE=0.001). In the rs-FC analysis, the WHOQOL_tot score was significantly linked to ROI-to-ROI connectivity: specifically, WHOQOL_tot was negatively correlated with brain connectivity between the bilateral Cerebellum and bilateral Putamen, Amygdala, left Nucleus Accumbens, and Caudate. Conversely, it was positively correlated with connectivity between bilateral Hippocampi and Parahippocampal cortices, as well as the left superior and middle Frontal gyrus and Frontal pole.

Conclusions

These findings demonstrate the correlation between QOL and brain structural and functional impairments in patients with MDD. Elevated levels of QOL are linked to increased brain volume; furthermore, diminished brain connectivity was observed between regions implicated in emotional processing, while enhanced connectivity was noted between regions associated with cognitive functions. These results imply that a supportive, low-stress environment may positively influence brain architecture, whereas decreased brain connectivity could signify heightened neuroplasticity.

References

References

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