2026 ECNP Congress

PS02-2260

Working memory deficits and brain network reconfigurations following stress in major depressive disorder with childhood trauma

Caroline Broeder — J.M. Pasteuning, T.A.A. Broeders, F. Linsen, M. Barrantes-Cepas, M.D.A. Bet, M.S.C. Sep, M.M. Schoonheim, C.H. Vinkers · Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Psychiatry, Amsterdam, Netherlands

2026 ECNP Congress

Background

Childhood trauma (CT) is a major risk factor for major depressive disorder (MDD) and is linked to stress system dysregulation and cognitive deficits. Working memory (WM) deficits and alterations in large-scale functional brain networks during WM performance are consistently observed in both MDD and CT, as well as following stress. However, the impact of stress on WM and brain network reconfigurations in MDD and CT remains underexplored. This study investigated WM performance and WM-related brain network reconfigurations following stress in individuals with MDD and CT compared to non-clinical controls without CT.

Methods

The sample consisted of 63 adults with moderate to severe MDD and CT and 37 controls.Participantsperformed N-back taskswith four WM load levels (0-, 1-, 2-, and 3-back) duringfunctional magnetic resonance imaging (fMRI) at acute (~15 minutes) and delayed (~135 minutes) timepoints following acute psychosocial stress induction (Trier Social Stress Test). In between sessions, there was a 60-minute rest period. Task performance (accuracy, mean reaction time) and functional connectivity (eigenvector centrality, within- and between-network connectivity, whole-brain connectivity) were assessed at both timepoints, and acute-to-delayed trajectories were compared between groups. Subjective stress responses (tension and affect) were assessed using 10-point visual analog scales.

Results

Both groups showed a significant increase in self-reported tension and negative affect following stress induction, with individuals with MDD and CT showing a greater increase in tension than controls (t(96.63) = 2.44,pfdr = 0.015) while no group difference was observed for negative affect (pfdr = 0.087). Individuals with MDD and CT showed lower accuracy than controls (β = −0.447, SE = 0.154, pfdr = 0.009), with a group × phase interaction indicating reduced accuracy during acute stress, while controls remained stable (β = 0.290, SE = 0.119, pfdr = 0.034). Across timepoints, the MDD with CT group exhibited increased deep gray matter (DGM) network centrality (β = 10.796 × 10-5, SE = 3.081 × 10-5, pfdr = 0.008) and reduced whole-brain connectivity (β = -0.128, SE = 0.034, pfdr = 0.008). No differences in functional brain connectivity between acute and delayed timepoints were observed within either group (all pfdr ≥ 0.058).

Conclusions

MDD with CT is associated with WM deficits, particularly during acute stress, along with increased DGM centrality and reduced whole-brain connectivity during WM performance across acute and delayed stress phases. These findings highlight both increased vulnerability to stress-induced cognitive deficits and the role of altered neural processing in cognition in MDD with CT. Future research should aim to systematically disentangle the effects of MDD and CT and assess whether these alterations extend to other cognitive domains. Ultimately, this could help identify individuals at elevated risk for persistent cognitive deficits who could benefit from early cognitive assessment and targeted interventions to preserve or improve cognitive function.

References

No references