Genetics and genomics in neuropsychopharmacology: the impact on drug discovery and development

Abstract

Genomics, the complete tabulation of all the genes in an organism, has made a major impact on the organisation of fully-integrated pharmaceutical companies. Drug discovery begins with bioinformatic elucidation of a human sequence encoding a potential drug target, followed by cloning and expression of the gene in a format for high throughput screening. Target validation is aided by reference to homologous genes in subhuman species as well as production of transgenic animals. In contrast, the impact of genetics on neuropsychopharmacology has been modest. It is interesting to compare the experience of genetics in the two major clinical disciplines dealing with disorders of the nervous system. Neurology has been at the forefront of human genetics with over 600 disorders mapped, of which causative mutations have been assigned to about 200 Mendelian disorders, each individually rare. Psychiatric genetics has been based on two log fewer diagnoses use of which has only yielded complex segregation patterns, a plethora of weak associations and no gene assignments. In neither case has genetics resulted in the development of a novel therapeutic agent. However, by refinements in diagnosis and genetic technology the promise for the future is great, not only for drug discovery, but also for subsequent preclinical and clinical development.