Postmortem Brain Tissue for Drug Discovery in Psychiatric Research

Extract

Schizophrenia, bipolar disorder, and severe depression are common and extremely disabling diseases thought to be caused by an interaction of genetic and environmental factors. Medications currently available to treat these diseases produce varying degrees of symptom amelioration in most patients but often cause unwanted side effects. The need for more effective medications with fewer side effects is universally acknowledged.

Many of the medications currently available, such as lithium and chlorpromazine, were discovered through serendipitous observation. However, there are more rational and reliable approaches to drug discovery. One approach is to identify genes and proteins thought to be etiologically involved in the disease and then identify the molecular pathways associated with these genes and proteins. Once putative disease pathways or mechanisms have been identified, chemical and molecular libraries can be screened for effective compounds. This approach may also identify molecular pathways impacted by existing medications used to treat other diseases. This approach, called “repurposing,” is evident in current trials, such as one using a gout drug, allopurinol, to treat schizophrenia. Another approach is to develop animal models of symptoms, such as the rodent-forced swim test for depression, and then identify compounds that improve it. Finally, one can identify environmental factors thought to interact with the predisposing genes, such as an infectious agent, and treat these factors.