Hippocampal-prefrontal functional magnetic resonance imaging signature of suicidal ideation in major depressive disorder

• Published in: Journal of affective disorders Vol. 391; p. 120019
• Main Authors: An, Xiao-Yuan, Guo, Zhi-Peng, Tang, Li-Rong, Gao, Yue, Wang, Na, Li, Ping, Liu, Chun-Hong
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.12.2025
• Subjects: Fractional amplitude of low-frequency fluctuations; Hippocampus; Major depressive disorder; Orbitofrontal cortex; Psychiatric/Mental Health; Regional homogeneity; Resting-state functional magnetic resonance imaging; Suicidal ideation; Fractional amplitude of low-frequency fluctuations; Orbitofrontal cortex; Regional homogeneity; Suicidal ideation; Resting-state functional magnetic resonance imaging; Major depressive disorder; Hippocampus
• ISSN: 0165-0327; 1573-2517; 1573-2517
• DOI: 10.1016/j.jad.2025.120019

Although suicidal ideation (SI) represents a critical manifestation associated with major depressive disorder (MDD), existing diagnostic methods remain largely subjective. This study adopted resting-state functional magnetic resonance imaging techniques to examine objective neural biomarkers connected to SI in patients with MDD. Participants comprised 50 patients with MDD and SI (MDD-SI), 56 patients with MDD without SI, and 55 healthy control individuals (HCs), matched by demographic variables. Regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuations (fALFF) analyses were conducted to characterize brain activity patterns. The detected neural features underwent independent clinical correlation and support vector machine (SVM) analyses to evaluate their clinical and diagnostic relevance. In MDD-SI subjects, elevated fALFF was observed in the middle frontal and right postcentral gyri, with a marginal increase in the left hippocampus. They exhibited unique hyperactivation in the right orbitofrontal cortex (OFC) as measured by ReHo, distinguishing them from patients with HCs and MDD without SI. Among individuals in the SI group, left hippocampal fALFF exhibited a significant negative association with depression severity scores (p < 0.05). The SVM classifier reached 63.81 % accuracy in distinguishing MDD-SI individuals from HCs based on ReHo in the right lateral OFC. The study provides novel evidence for distinct neural substrates underlying SI in MDD, highlighting the involvement of hippocampal-prefrontal circuits and sensory integration regions. Despite limitations related to cross-sectional design and medication effects, the findings enhance the understanding of suicide-related brain changes and may aid in identifying biological markers of suicide risk. [Display omitted] •Unique hippocampal-prefrontal-orbitofrontal hyperactivity patterns in suicidal MDD•Hippocampal hyperactivity inversely correlates with depression in suicidal MDD.•Postcentral gyrus activity differentiates suicidal from non-suicidal depression.