Is there a link between TNF gene expression and cognitive deficits in depression?

Area of Science:

• Neuroscience
• Immunology
• Genetics

Background:

• Neuroinflammation plays a role in recurrent depressive disorders (rDD).
• Depression is associated with activated immune-inflammatory pathways, including elevated Tumor Necrosis Factor-alpha (TNF-α), soluble TNFRSF1A (sTNFR1), and soluble TNFRSF1B (sTNFR2).

Purpose of the Study:

• To analyze TNF-α, TNFRSF1A, and TNFRSF1B gene expression at mRNA and protein levels in rDD patients.
• To investigate the relationship between the expression of these genes and cognitive performance in rDD patients.

Main Methods:

• The study included 158 participants: 89 with rDD and 69 healthy controls (HS).
• Cognitive function was assessed using the Trail Making Test, Stroop Test, Verbal Fluency Test, and Auditory Verbal Learning Test (AVLT).
• mRNA and protein levels of TNF-α, TNFRSF1A, and TNFRSF1B were measured.

Main Results:

• Significantly higher mRNA and protein expression levels of TNF-α, TNFRSF1A, and TNFRSF1B were observed in rDD subjects compared to HS.
• No significant correlations were found between analyzed variables in the rDD group and HS group, except for a negative correlation between TNFRSF1A/TNFRSF1B gene expression and AVLT performance in the HS group.
• Statistically significant correlations were observed between TNF, TNFRSF1A, TNFRSF1B mRNA gene expression and all neuropsychological tests for the entire group.

Conclusions:

• The study demonstrates increased expression of TNF, TNFRSF1A, and TNFRSF1B genes on both mRNA and protein levels in depression.
• Elevated expression of TNF-α, TNFRSF1A, and TNFRSF1B negatively correlates with cognitive efficiency, including working memory, executive functions, attention, auditory-verbal memory, learning processes, and verbal fluency.