STRATEGIES FOR SELECTING TARGETS FOR DRUG DEVELOPMENT IN SCHIZOPHRENIA

in schizophrenia and in mood disorder diagnoses have been available since the

mid 1950s. We have both first and second generation medications for clinical

use.  These treatments have provided unmeasurable help to persons with

these illnesses.  However, treatments were developed serendipitously and

without the full mechanism of their antipsychotic actions known.  Now,

however, broad and critical basic neuroscience knowledge is available and

clinical research techniques have been developed, both of which promise new

opportunity for treatment development.  Guiding strategies for

identification of primary targets for drug development must start with clinical

knowledge about the illnesses in order to maximize their ultimate

effectiveness.  New concepts from genetics, molecular biology, and from

brain imaging studies should be applied with viable clinical constructs.  I

will discuss a broad strategy utilized in my research, beginning with illness

demographics to structure the research question.  The application of

functional imaging techniques to identify critical cerebral regions of

dysfunction in the illness are important.  Then, a full identification of

anatomic and neurochemical changes within those regions can produce relevant

information.  Our data suggest that the limbic cortex, especially the

hippocampus, functions to mediate psychotic phenomena in schizophrenia and may

be involved in other psychotic illnesses as well.  Both glutamatergic,

GABergic and the monoamines are important in the function of the limbic cortex

and could be primarily or secondarily involved in psychosis

pathophysiology.  The use of human postmortem tissue in the study of CNS

pathophysiology has become vital to advances in identification of

pathophysiology.  These kinds of strategies ought to provide our field with