The interplay between polygenic score for tumor necrosis factor-α, brain structural connectivity, and processing...

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• Major depressive disorder (MDD) is characterized by cognitive deficits, notably reduced processing speed.
• Structural brain network alterations and genetic-immunological factors are implicated in MDD.
• Tumor necrosis factor-α (TNF-α) plays a role in inflammation and has been linked to depressive symptoms.

Purpose of the Study:

• To investigate the association between polygenic scores for TNF-α blood levels (TNF-α PGS), structural brain connectivity, and processing speed in MDD patients.
• To determine if structural brain connectivity mediates the relationship between TNF-α PGS and processing speed in acute MDD.

Main Methods:

• Utilized a large sample including acutely depressed, remitted MDD patients, and healthy controls (HC).
• Assessed processing speed using five neuropsychological tests.
• Employed network-based statistics to identify brain networks and general linear models to analyze associations and mediation effects.

Main Results:

• A structural brain network positively associated with processing speed was identified.
• A significant negative association was found between TNF-α PGS and processing speed in acutely depressed patients, but not in remitted patients or HC.
• Brain connectivity partially mediated the association between TNF-α PGS and processing speed in acute MDD.

Conclusions:

• TNF-α PGS is associated with decreased processing speed in acute MDD, suggesting a role for genetic-immunological factors.
• Structural brain connectivity partially mediates this relationship, underscoring its importance in cognitive dysfunction in MDD.
• These findings contribute to understanding the pathomechanisms of cognitive deficits in MDD using multimodal data.