ORIGINAL RESEARCH article
Front. Aging Neurosci.
Sec. Neurocognitive Aging and Behavior
This article is part of the Research TopicBiomarkers in Aging Psychiatry: From Diagnostic Tools to Therapeutic IndicatorsView all 4 articles
Cross-sectional and longitudinal functional network alter-ations associated with subthreshold depressive symptoms in healthy older adults
Provisionally accepted
Julia Christl1*
Pascal Grumbach2
Camilla Mendl-Heinisch2
Christiane Jockwitz2
Eva Meisenzahl2Svenja Caspers2- 1LVR Hospital Essen, Essen, Germany
- 2Heinrich-Heine-Universitat Dusseldorf Medizinische Fakultat, Düsseldorf, Germany
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Abstract Objective: Subthreshold depressive symptoms (SDS) in older adults as a prodromal state of late-life depression (LLD) increase with age and are associated with elevated risk for cardio-and cerebrovascular diseases. LLD has been linked to functional brain network disruptions, including the ventral attention (VAN) and default mode network (DMN). Thus, identifying alterations in functional connectivity (FC) linked to SDS may be critical for the early detection and treatment of individuals at high-risk for LLD. Methods: A total of 243 healthy older subjects (55-84 years; MAge = 67.0 ± 6.5) without a history of depression and current antidepressant intake from the 1000BRAINS sample with two timepoints of assessments were included in this study (time interval = 3.7 ± 0.7 years). SDS were measured using the Beck Depression Inventory II (BDI-II < 20) and linked to resting-state functional magnetic resonance imaging derived FC within and between seven large scale functional brain networks. Results: Both cross-sectional and longitudinal analyses revealed that SDS were associated with decreased intra-and inter-network FC. After Bonferroni correction for multiple comparisons, reduced FC within the VAN at baseline significantly predicted a longitudinal increase in depressive symptoms. This association was primarily driven by the somatic symptom domain of the BDI-II. Post-hoc analyses highlighted the particular involvement of right-hemispheric VAN regions. Conclusion: Our findings support the hypothesis that even minimal to mild depressive symp-toms in older adults are linked to disrupted functional network architecture. Specifically, reduced FC within the VAN may serve as an early neural marker for the emergence of depressive symptoms and vulnerability for the progression into clinically manifest LLD. Thus, offering potential for early detection and targeted intervention in subjects at high risk.
Keywords: Early detection, functional connectivity, late-life depression, subthreshold depressive symptoms, ventral attention network
Received: 08 Nov 2025; Accepted: 09 Feb 2026.
Copyright: © 2026 Christl, Grumbach, Mendl-Heinisch, Jockwitz, Meisenzahl and Caspers. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Julia Christl
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