Lower resting state functional connectivity between the hippocampus and default network is associated with suicidal ideation

J Affect Disord. 2026 May 20:122005. doi: 10.1016/j.jad.2026.122005. Online ahead of print.

ABSTRACT

Suicidal ideation (SI) is a clinical risk factor for suicidal behavior. Elucidating the neural mechanism underlying SI may lay the groundwork for future methods for its assessment. Our group previously showed that SI is associated with altered resting hippocampal activity, as measured using functional magnetic resonance imaging Amplitude of Low Frequency Fluctuations (ALFF). However, the role of hippocampal functional connectivity (FC) in SI has not been fully characterized. Here, we compared resting-state FC data in unmedicated adult participants experiencing a major depressive episode and SI compared with those without SI. The previously identified hippocampal region of higher ALFF in individuals with SI was used as a seed region of interest (ROI), and we examined its whole-brain functional connectivity pattern. Across the entire sample, the hippocampal ROI connectivity pattern had a spatial distribution consistent with the Default Network (DN). FC from the hippocampal ROI to DN was lower in participants with SI (n = 24) compared with those without SI (n = 10), suggesting reduced coupling with DN. Intra-network FC between all the DN regions was not significantly associated with SI, suggesting a more specific association with hippocampus connectivity. The FC result was examined in a larger, publicly available dataset, REST-MDD. FC of the right hippocampus to DN was lower in participants with SI (n = 158) compared with those without SI (n = 60), demonstrating a cross-dataset convergence. These results indicate that hippocampal resting connectivity is associated with the presence of SI. Future studies using longitudinal designs should examine how changes in clinical status influence this FC pattern.

PMID:42167697 | DOI:10.1016/j.jad.2026.122005