Figure 4. Genes differentially expressed between responders and non-responders were enriched in transcriptional networks of hepatocyte nuclear factor (HNF) 4-alpha and nuclear factor-kappaB (NF-kB), early and late following the initial infliximab infusion, respectively.

Infliximab (5mg/kg, n=30) was administered over 12 weeks through an indwelling catheter at baseline, 2 weeks and 6 weeks, and antidepressant response was determined as a 50% reduction in depression severity as measured by the 17-item HAM-D at any time point during the study. Genes that were differentially regulated in responders compared to non-responders were analyzed at 6 hr, 24 hr, and 2 weeks. 6 hr after infliximab, the transcriptional network for HNF4-alpha was composed of mostly of genes up-regulated (red circles, 13/21 genes) in responders compared to non-responders (A), whereas at 24 hr, the transcriptional network for HNF4-alpha was comprised mostly of genes down-regulated in responders (blue circle, 20/24 genes) (B). 2 weeks after the initial infliximab infusion, the genes differentially regulated in responders versus non-responders were enriched in the NF-kB transcriptional network and comprised mostly of down-regulated genes (blue circle, 8/11 genes) (C). Red circle= up-regulated genes; Blue circle= down-regulated genes; orange arrowhead= enzyme; red arrowhead= lipid kinase; pink X= transporter; red star= transcription factor; turquoise Y= receptor; blue S =binding protein; blue clover =protein, green double-headed arrow=RAS superfamily; pink and brown H=channel; green down arrow=regulator; orange arrowhead with hole=protease; green T= receptor ligand.