Hippocampal subfield functional connectivity alterations in major depressive disorder: A systematic review and meta-analysis.
Yulong Liu, Yu Chen, Min Kong et al.
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In 30 seconds
This systematic review and meta-analysis examined functional connectivity (FC) involving hippocampal subfields or subregions in major depressive disorder (MDD), comparing findings with healthy controls and summarizing treatment-related studies. Eighteen studies included 1366 patients with MDD and 935 healthy controls; five contributed to exploratory network-specific meta-analyses. FC was lower in MDD for hippocampal subregion-default mode network connections (g = -0.74, 95% CI -0.98 to -0.50) and visual network connections (g = -0.64, 95% CI -0.94 to -0.34). Findings across other networks and narrative studies were heterogeneous.
Key findings
- Meta-analysis found lower hippocampal subregion-default mode network FC in MDD (g = -0.74, 95% CI -0.98 to -0.50).
- Hippocampal subregion-visual network FC was also lower in MDD (g = -0.64, 95% CI -0.94 to -0.34).
- Estimates for salience, limbic, and sensorimotor networks were imprecise and heterogeneous.
- Segmentation approaches varied substantially in hippocampal coverage and granularity; narrative findings were bidirectional.
Why it matters
The findings suggest that hippocampal connectivity differences in MDD may depend on the subregion and connected network, rather than reflecting a uniform abnormality. However, variation in segmentation methods and heterogeneous results limit interpretation across studies. More harmonized, method-aware approaches may help clarify which connectivity patterns are reproducible and clinically informative.
What to keep in mind
Only five studies contributed to exploratory network-specific meta-analyses, and segmentation methods differed substantially. Estimates for several networks were imprecise and heterogeneous.