Abstract:

Several microarray-based studies have investigated gene expression profiles in major depressive disorder (MDD), yet with highly variable findings. We examined blood-based genome-wide expression signatures of MDD, focusing on molecular pathways and networks underlying differentially expressed genes (DEGs) and behaviours of hypothesis-driven, evidence-based candidate genes for depression. Agilent human whole-genome arrays were used to measure gene expression in 14 medication-free outpatients with MDD who were at least moderately ill and 14 healthy controls matched pairwise for age and sex. After filtering, we compared expression of entire probes between patients and controls and identified DEGs. The DEGs were evaluated by pathway and network analyses. For the candidate gene analysis, we utilized 169 previously prioritized genes and examined their case-control separation efficiency and correlational co-expression network in patients relative to controls. The 317 screened DEGs mapped to a significantly over-represented pathway, the "synaptic transmission" pathway. The protein-protein interaction network was also significantly enriched, in which a number of key molecules for depression were included. The co-expression network of candidate genes was markedly disrupted in patients. This study provided evidence for an altered molecular network along with several key molecules in MDD and confirmed that the candidate genes are worthwhile targets for depression research.

日本語要旨:

うつ病は遺伝要因と環境要因が複雑に相互作用することで発症する疾患である。本研究では、服薬していないうつ病患者と健常対照者においてマイクロアレイを用いた網羅的遺伝子発現研究を行い、うつ病において発現が変動する遺伝子を特定した。さらに、これらの発現変動遺伝子に対して詳細なバイオインフォマティクス解析を行い、うつ病の病態に関与する複数の遺伝子とそれらの相互作用ネットワークを見出した。