Neurochemical and genetic bases of psychopathology: future directions

It is widely recognized that biological psychiatry must deal with the problem of resolving heterogeneous syndromes into homogeneous subtypes. In order to gain insight into this process, we studied the history of research on cerebellar ataxia, a group of neurological disorders which originally presented a problem of heterogeneity very similar to that found in psychiatry. In the ataxias, effective classification required neuropathological examination in addition to observation of symptoms, clinical course, and pattern of inheritance. Nevertheless, in the ataxias, neuropathological work still left overlap and uncertainty. Modern biochemical and genetic progress on the ataxias would have been much more difficult, however, had this preliminary neuropathological classification not been worked out. Analogies are drawn to contemporary research in psychiatry.