Fifteen years of human genetics studies of schizophrenia and bipolar disorder, have yielded insights into their molecular mechanisms. Using these insights I have initiated a longitudinal multisite and multi-sector study (including industry and government partners) of biomarkers in cerebrospinal fluid and plasma of people with these disorders. Participants have been genotyped, and return at regular intervals for evaluation of symptoms, cognition, and functioning. At yearly intervals they undergo structural and resting state MRI, and to donate biological samples (cerebrospinal fluid, blood, and blood cells to generate induced pluripotent cell lines). Parallel studies are being initiated with collaborators in Finland where we jointly study a cohort of 10,000 affected individuals. Proteomic studies to date are yielding data consistent with some hypotheses from the genetics related to synapse loss, and some interesting surprises.