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Preserved Memory performance despite reduced hippocampal volume in treatment-resistant depression

Poster Session E - Monday, March 9, 2026, 2:30 – 4:30 pm PDT, Fairview/Kitsilano Ballroom
Also presenting in Data Blitz Session 2 - Saturday, March 7, 2026, 10:30 am – 12:00 pm PST, Salon D.

Claire Lauzon^1,2 (), Angelina Zhang², Tulip Marawi^2,3, Georgia Gopinath⁴, Isabella J. Sewell¹, Sean M. Nestor², Peter Giacobbe², R. Shayna Rosenbaum¹, Jennifer S. Rabin^2,3; ¹York University, ²Sunnybrook Research Institute, ³University of Toronto, ⁴University of Manitoba

Individuals with depression show reduced hippocampal volumes compared to non-depressed controls, perhaps driven by volumetric reductions in the dentate gyrus (DG). Bilateral lesions to the DG are associated with impaired performance on mnemonic discrimination tasks, but it is unknown whether hippocampal subfield changes contribute to memory difficulties in depression. We examined individuals with treatment-resistant depression (TRD; n = 12, 6 males, mean age = 40.3, education = 14.8 years) and non-depressed controls (n = 15, 8 males, mean age = 36.5, education = 16.2 years). Participants underwent a 3T MRI brain scan, including a high-resolution T2-weighted scan of the hippocampus, and completed a battery of neuropsychological tests including two mnemonic discrimination tasks. Hippocampal volume was significantly reduced in individuals with TRD compared to controls (p=.002, η²=0.38), and smaller hippocampal volume was associated with greater depression severity across the entire sample (β=-42.19 mm3, p=.021, assessed using the Questionnaire for Depressive Symptoms). These reductions were localized to the hippocampal body (DG/CA3/CA2, CA1, and subiculum), whereas extrahippocampal regions did not differ between groups. No group differences were observed in mnemonic discrimination or other memory tasks, though higher depression scores were associated with poorer performance on other neuropsychological measures, including Trails B (β=3.0, p=.028) and Phonemic Fluency (β=-0.78, p=.035). Individuals with TRD showed reduced hippocampal subfield volumes, particularly in the dentate gyrus and adjacent regions. These reductions were linked to greater depression severity but not to memory performance, suggesting hippocampal atrophy in depression might reflect mood-related rather than mnemonic processes.

Topic Area: LONG-TERM MEMORY: Episodic