S.06.01 Multi-omics profiling approaches to biomarker discovery in bipolar disorder

Major depressive disorder (MDD) and bipolar disorder (BD) are debilitating mental diseases. Currently the diagnosis of these disorders is only based on subjective clinical assessments and the identification of molecular biomarkers could contribute to improved understanding of the underlying pathophysiological pathways. In turn, this could lead to more accurate empirical diagnoses and improved treatment strategies. Recently we carried out central (post mortem) and peripheral (blood) molecular profiling on MDD and BD patients. Shotgun proteomic analysis of dorsolateral prefrontal cortex samples from MDD patients (+/− psychosis) revealed alterations associated with energy metabolism and synaptic function. Interestingly, the psychosis proteomics changes showed a marked overlap with brain proteome profiles of schizophrenia patients. Separate analysis of post mortem pituitary and hippocampal proteome profiles of BD patients showed disruption of hormones, core histones and mitochondrial pathways. Proteome analysis by multiplexed immunoassay analysis of plasma from 25 BD mania patients showed hormonal dysregulation and disturbances in energy and lipid metabolism. Mass spectrometry analysis of plasma from 17 BD mania patients identified changes in inflammatory and coagulation proteins. We then followed up 13 patients after they experienced a manic episode and this revealed marked suppression of plasma pro-inflammatory markers. Ultimately, further molecular and functional investigations could lead to increased understanding of these disorders and help to distinguish different subtypes these broad psychiatric classifications. In turn, this could lead to novel approaches for drug target identification and discovery strategies.