In the first half of the last century researchers believed that severe mental disorders like schizophrenia have a neuropathological basis. Up to now it has been difficult to prove any consistent core finding for this disorder. Reason for this might be that it is a network disorder and therefore regional specific findings will unlikely be found. Parallel to that describing the dopamine hypothesis of schizophrenia and the catechol amine deficit hypothesis of depression were very helpful for understanding the mechanisms of antipsychotics and antidepressants working in these disorders. Especially the introduction of the positron emission tomography has helped to link symptoms with the transmitter systems. However, none of these findings are specific for schizophrenia or depression. During the talk it will be discussed when the combination of core clinical symptoms, imaging findings and genetic variables are helpful for a future classification of psychiatric disorders.