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Sex differences in brain activity and connectivity in late-life depression
Xiaomin Zheng1,2, Ben Chen2, Mingfeng Yang2
1The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong Province, 510515, China.
Psychoradiology
|February 13, 2026
Summary
Sex differences in late-life depression (LLD) impact brain activity, cognitive function, and symptom severity. Understanding these sex-specific neurobiological underpinnings is crucial for targeted LLD treatments.
Area of Science:
- Neuroscience
- Gerontology
- Psychiatry
Background:
- Late-life depression (LLD) exhibits notable sex differences in symptoms and treatment response.
- Underlying static and dynamic brain function abnormalities driving these disparities remain unclear.
- This study investigates sex-specific aberrant brain activity in LLD.
Purpose of the Study:
- To investigate sex-specific aberrant brain activity in late-life depression (LLD).
- To explore sex differences in static and dynamic brain function metrics in LLD.
- To examine the moderating role of sex in the relationship between brain activity, cognition, and depressive symptoms in LLD.
Main Methods:
- Recruited 75 LLD patients and 164 healthy controls (HCs).
- Compared static and dynamic metrics of ALFF, ReHo, and FC across four groups (LLD-female, LLD-male, HC-female, HC-male).
- Utilized correlation and moderation analyses to assess sex effects on brain activity, cognition, and depressive symptoms.
Main Results:
- Significant interactions between diagnosis and sex were found for ALFF, ReHo, and static FC.
- In LLD females, ReHo and sFC correlated with weight, and ALFF correlated with visuospatial skills.
- Sex moderated relationships between ReHo, ALFF, sFC, and cognition/depressive symptoms in the LLD group.
Conclusions:
- Highlights significant sex differences in static brain activity in LLD.
- Reveals sex-specific neurobiological underpinnings related to cognitive impairment and depressive symptoms in LLD.
- Suggests the importance of considering sex as a biological variable in LLD research and treatment.
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