Peripheral immune-redox signatures associate with cortical network alterations in anhedonic depression - PubMed
3 hours ago
- #depression
- #anhedonia
- #immune-redox
- Anhedonia is a core feature of major depressive disorder (MDD), with links between peripheral molecular signatures and cortical network architecture being poorly defined.
- The study involved 210 participants, including 56 unmedicated MDD patients with high-anhedonia (HA), 61 with low-anhedonia (LA), and 93 healthy controls (HC).
- Morphometric similarity networks (MSNs) from structural MRI were compared between HA and LA, showing greater MSN integration in HA, particularly within default-mode and somatomotor networks.
- MSN maps were negatively correlated with dopamine-transporter and kappa-opioid-receptor densities.
- Imaging-derived gene associations were enriched for regulation of Toll-like-receptor-3 signaling.
- Whole-blood RNA-seq analysis revealed coupling between MSN features and a transcriptomic signature enriched for T-cell activation/differentiation and lymphocyte-apoptosis pathways.
- After leukocyte-composition adjustment, the pre-specified blood signature did not differ between HA and LA, indicating that between-group differences were largely composition-driven.
- Peripheral immune-redox pathway enrichment aligns with anhedonia-related cortical network alterations, whereas between-group blood differences are chiefly composition-driven.
- The study suggests immune-modulatory/redox targets and synaptic-adhesion biology for precision stratification and intervention in anhedonic depression.