Phase-specific differential gene expression of peripheral blood mononuclear cells in rapid cycling syndrome

Molecular mechanisms underlying bipolar affective disorders, in particular rapid cycling, are unknown. We analyzed peripheral blood mononuclear cells (PBMC) of one individual patient with rapid cycling syndrome under widely standardized conditions. RNA was extracted from PBMC of eight blood samples, obtained on two consecutive days (8.00 am, overnight fast) within one particular phase, including two different consecutive depressive and manic phases, and submitted to screening by microarray hybridizations, followed by detailed bioinformatic analysis. Phase-specific regulation of genes was confirmed by quantitative RT-PCR, and validated in additional blood samples obtained over one year later. Among the phase-specific differentially expressed genes were genes involved in the regulation of the innate immune response by different mechanisms, neurodevelopmentally important genes, genes involved in prostaglandin metabolism and genes encoding the hemoglobins A and B. This case demonstrates a consistent phase-dependent alteration in PBMC gene expression in rapid cycling which might partly explain some of the concomitant clinical features, like allergic diathesis. Whether phase-specific regulation of neurodevelopmental genes in PBMC reflects parallel regulation of these genes in the brain remains open.