Fig. 1: The reverse translation approach to biomarker discovery.
The heterogeneous group of mental illness patients lacks a clear biology-based clinical categorization which impedes attempts for the discovery of objective biomarkers so far. By defining biological subgroups based on human neuropathobiochemistry, in our case misassembled DISC1 protein in post mortem brain9, we were able to design a transgenic rat model for this specific subset16 that demonstrated aberrant signaling networks of key pathways relevant for schizophrenia27. Utilizing this animal model as a prototype for subtly deranged signaling networks essential for behavioral control, peripheral markers were identified in this animal model which, in a so-called “reverse translational approach”, were translated back into schizophrenia patient cohorts, coming full circle for defining subsets of mental illness patients
