Abstract
Based on global transcriptomic profiles from an 8x60K human microarray, we selected NR4A1 (Nuclear Receptor Subfamily4GroupAMember1) and KCNK17 (Potassium Channel Subfamily K Member 17) as candidates for molecular analysis.
We included 308 patients experiencing an ongoing episode of depression, either as part of UD or BD, and 353 healthy control subjects. In this pilot study, we used screening expression microarrays to assess genes with differential expression in unipolar and bipolar depression. We genotyped NR4A1 (rs2242107) & KCNK17 (rs9471058) polymorphisms, and measured changes in the serum concentration of both proteins using ELISA methods. We compared serum concentrations during acute states of depression with levels recorded after the improvement of symptoms.
We observed upregulation of 4 genes (GSTT2, IGSF23, KCNK17, HRK) and downregulation of 7 genes (BTC, NR4A1, OLIG3, SPATA21, CFB, SPTBN4, RTP2) in BD patients compared to UD patients. NR4A1 serum RNA levels in depression patients were slightly higher during depressive episodes than during remission. The serum concentration of KCNK4 RNA was below detection level in both groups. We did not find any significant differences in genotyping distribution between case and control individuals even after adjusting by gender and type of disease for both polymorphisms.
Using leukocyte gene expression profiles, we could accurately distinguish depression type in patients with UD and BD. In light of the results we obtained from serum level tests, and prior indications that NR4A1 may participate in mitochondrial function and thus in synaptogenesis, its activity appears to be an attractive biomarker for depression and other psychiatric disorders.