Altered choroid plexus gene expression in major depressive disorder.

Area of Science:

• Neuroscience
• Molecular Biology
• Biomarker Discovery

Background:

• Major depressive disorder (MDD) lacks definitive biomarkers.
• The choroid plexus (CP) produces cerebrospinal fluid (CSF) and may harbor MDD-related biomarkers.
• Previous studies indicated fibroblast growth factor family dysregulation in MDD brain tissue.

Purpose of the Study:

• To investigate gene expression differences in the CP between MDD patients and controls.
• To identify potential CSF biomarkers for MDD.
• To explore the role of growth factors and pathways in the CP in MDD.

Main Methods:

• Laser capture microscopy of CP tissue from MDD patients and controls.
• RNA extraction, amplification, labeling, and hybridization to Illumina BeadChips for gene expression analysis.
• Bioinformatic analysis including pathway analysis and quantitative real-time PCR (qRT-PCR).

Main Results:

• 169 transcripts were differentially expressed between control and MDD samples (p < 0.05).
• The transforming growth factor-beta (TGFβ) pathway was significantly altered in MDD subjects.
• Downregulation of extracellular matrix-interacting transcripts was confirmed by qRT-PCR, suggesting cytoskeleton alterations.

Conclusions:

• Gene expression in the CP is altered in MDD.
• The TGFβ pathway and cytoskeleton may be implicated in MDD pathophysiology.
• CP gene expression changes may indicate a disrupted blood-CSF-brain barrier in MDD, offering potential biomarker avenues.