ABSTRACT
The concept of schizophrenia was developed a century ago by Kraepelin and Bleuler based on clinical description, and 60 years later linked to the neurobiology of the dopamine (DA) system via the discovery of antipsychotic drugs. For several decades, this state of affairs left psychiatry in a highly unsatisfactory situation regarding one of its most prominent disorders. On the one hand, the disorder is characterized by profound changes in the way a person relates to the environment and experiences self, other people and the world. On the other hand, it is treated with substances that act upon a pathway within the brain whose function was hardly known for decades, except for its roles in motor and neuroendocrine function, which are related to the side effects, but not to the therapeutic effects of the drugs. Recent discoveries regarding the function of the prefrontal cortex and the mesocortical and mesolimbic dopaminergic pathways provide a thread to relate these findings to the psychopathology of schizophrenia. Models of neuronal functioning at the systems level have reached a degree of sophistication such that, for the first time, they have clinical implications for the treatment of schizophrenia.
