Transcriptomic predictors of inflammation-induced depressed mood.

Area of Science:

• Neuroscience
• Immunology
• Genetics

Background:

• Inflammation is implicated in depression pathophysiology.
• Identifying individuals susceptible to depression following inflammatory challenges is crucial for targeted interventions.

Purpose of the Study:

• To investigate whether leukocyte transcriptome profiles at baseline predict inflammation-induced depressed mood.
• To identify specific transcription factor (TF) activities associated with heightened depression risk after endotoxin administration.

Main Methods:

• A randomized, double-blind, placebo-controlled study involving 115 volunteers.
• Baseline genome-wide transcriptional profiling of peripheral blood mononuclear cells to assess TF activities.
• Administration of low-dose intravenous endotoxin and assessment of depressed mood using the Profile of Mood States.

Main Results:

• 36% of participants experienced increased depressed mood post-endotoxin.
• Baseline activity of TFs related to immune activation (NF-kB) and sympathetic activation (CREB) predicted increased depressed mood.
• Decreased baseline activity of glucocorticoid receptor (GR)-related TFs also predicted depressed mood.

Conclusions:

• Peripheral transcriptome profiles, specifically TF activities, can predict inflammation-induced depressed mood.
• These findings suggest a genomic approach for identifying individuals at high risk for the inflammatory subtype of depression.