Cerebellum-cerebrum functional connectivity mediates the association between Adverse Childhood Experiences and suicidal behaviors in depressed adolescents

07/11/2025

J Affect Disord. 2025 Nov 4:120591. doi: 10.1016/j.jad.2025.120591. Online ahead of print.

ABSTRACT

BACKGROUND: As a form of trauma in early life stages, Adverse Childhood Experiences (ACEs) have been linked to various mental health issues, including depression and suicidal behaviors. Understanding the neurobiological mechanisms underlying these associations is crucial.

METHODS: A total of 127 depressed adolescents were recruited from Xuzhou Oriental People’s Hospital, including 34 adolescents with suicidal behaviors (SB) and 93 adolescents with non-suicidal behaviors (NSB). Additionally, 43 healthy controls (HC) were recruited from local communities and schools. We aimed to explore the associations between brain regions, ACEs, and psychological characteristics, as well as the mediating role of these differential brain regions in the relationship between ACEs and suicidal behaviors in depressed adolescents.

RESULTS: Significant changes in Amplitude of low-frequency fluctuations (ALFF), fractional ALFF, region homogeneity, degree centrality (DC), and function connectivity (FC) were observed among the three groups in multiple brain regions, including the supplementary motor area (P_FDR < 0.05). Post-hoc analyses revealed that, compared to the NSB, the SB group showed specific alterations in the cerebellum. Importantly, the DC values in the cerebellum, as well as FC with regions such as the postcentral gyrus, partially mediated the relationship between ACE or abuse and suicidal behaviors (P < 0.001).

LIMITATIONS: The longitudinal effect of ACEs on suicidal behaviors in depressed adolescents remains unclear.

CONCLUSIONS: Changes in function in depressed adolescents can mediate the relationship between ACE and suicidal behaviors. The affected brain regions are primarily located in the precuneus, supplementary motor area, cerebellum, and brain regions closely related to cerebellar function.

PMID:41197912 | DOI:10.1016/j.jad.2025.120591

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