At present, little is known about the basic mechanisms that underlie the schizophrenia disease process. This lack of knowledge is most likely due to the fact that until recently large-scale expression profiling studies were technologically impossible. Thus, most researchers employed a “candidate gene/protein” approach. With recent technological advances in genomics, proteomics and metabolomics techniques, it is now possible to globally investigate the molecular underpinnings of psychiatric conditions which should result in improved knowledge and hopefully new (pre-symptomatic) diagnostic, therapeutic and preventative regimes. My laboratory combines advanced computing and bioscience technologies with functional genomics studies. Using this powerful approach we explore the molecular “fingerprints” of psychotic disorders from early onset through their progressive stages, exploring alterations at the gene, protein, lipid and metabolite level. This in turn should reflect and reveal dynamic changes of interlinked pathways in the normal and disease brain. I will present results from our biomarker discovery studies. To date we have identified a number of highly significant peptides and metabolites that distinguish first-onset paranoid schizophrenia patients from healthy controls. Our findings suggest brain-specific alterations in glucoregulatory processes in the CSF of drug-naïve patients with first-onset schizophrenia, implying that these abnormalities are intrinsic to the disease, rather than a side effect of antipsychotic medication. Short-term treatment with atypical antipsychotic medication resulted in a normalization of the CSF disease signature in half the patients well before a clinical improvement would be expected. Furthermore, our results suggest that the initiation of antipsychotic treatment during a first psychotic episode may influence treatment response and/or outcome.