Putamen subregion dysfunction mediates the relationship between childhood maltreatment and major depressive disorder

Eur Arch Psychiatry Clin Neurosci. 2025 Jun 10. doi: 10.1007/s00406-025-02034-8. Online ahead of print.

ABSTRACT

Childhood maltreatment is a significant risk factor for the development of major depressive disorder (MDD) and is closely linked to abnormalities in the brain’s reward circuitry. Previous studies have observed reward circuitry abnormalities centered around the putamen in MDD patients, treating it as a single core nucleus. However, the putamen is a heterogeneous nucleus composed of different functional subregions, and there is limited research focused on the abnormal functional connectivity (FC) of putamen subregions in MDD with childhood maltreatment. To explore putamen-centered reward circuitry abnormalities in MDD with childhood maltreatment, we conducted static and dynamic functional connectivity (FC) analyses with putamen subregions (including the ventral anterior putamen, dorsal anterior putamen, ventral posterior putamen, and dorsal posterior putamen) as regions of interest. Four groups were included: MDD with childhood maltreatment (n = 48), MDD without childhood maltreatment (n = 30), healthy controls with childhood maltreatment (n = 57), and healthy controls without childhood maltreatment (n = 46). Compared to MDD without childhood maltreatment, MDD with childhood maltreatment exhibited higher dynamic FC between the right dorsal putamen and the right prefrontal gyrus, as well as lower static FC between the right ventral anterior putamen and the left middle frontal gyrus and left anterior cingulate gyrus. A positive correlation was found between these aberrant dynamic FC patterns and childhood maltreatment. Additionally, the abnormal dynamic FC mediated the relationship between childhood neglect and the depression severity. These findings suggest that dysfunctional connectivity within the putamen subregions may serve as a neurobiological marker for MDD in individuals with childhood maltreatment. This study contributes to a better understanding of the underlying neurobiological mechanisms of MDD, with implications for more targeted interventions that take into account the specific brain alterations associated with a history of childhood maltreatment.

PMID:40493215 | DOI:10.1007/s00406-025-02034-8