Genetic regulation of neurotransmitter enzymes and receptors: relationship to the inheritance of psychiatric disorders.

Abstract

This report begins with a summary of the evidence for genetic involvement in certain major psychiatric syndromes. The relation of these disorders to deficits in central nervous system neurotransmitters is also summarized. These reviews serve as an introduction to our studies on the genetic regulation of neurotransmitters and their enzymes and receptors in inbred mice. The steady-state levels of the adrenal catecholamine biosynthetic enzymes are controlled genetically; not only is each enzyme regulated by a single locus, but also there is statistical evidence that the phenotypic expression of the entire pathway is regulated by a single gene. Studies on the biochemical mechanism of gene action suggest that genetic regulation is exerted on proteolysis of the enzymes, rather than their synthesis. In addition, we have examined the genetic control of dopamine receptors in inbred mice. Dopaminergic receptors in the nigrostriatal and mesolimbic pathways are under genetic control. Preliminary evidence suggests that the pathways are regulated by different genetic systems. If this early speculation proves true, it would have important clinical implications.