Dr. Erminio Costa, M.D.

Dr. Erminio Costa, M.D.
Scientific Director, Psychiatric Institute
Professor of Biochemistry in Psychaitry
University of Illinois at Chicago (UIC)

Emigrating to America and finding his way

Dr. Erminio Costa has contributed to the initial development of the psychopharmacology of g amino butyric acid (GABA), the most important brain inhibitory transmitter. Its expression is downregulated in schizophrenia morbidity. Costa’s major contribution to psychopharmacology is related to the mode of action of the benzodiazepines. In collaboration with Dr. A. Guidotti, they pioneered research suggesting that these anxiolytic drugs act by positively and allosterically modulating the action of GABA on GABAA receptors. This finding is now universally confirmed and accepted. Working on the mechanisms of schizophrenia morbidity, Costa has marshaled correlated evidence indicating that the function of cortical GABAergic interneurons is downregulated in schizophrenia. Probably, this downregulation is related to an increased expression by these interneurons of DNA methyltransferase (DNMT1), which presumably hypermethylates promoters expressed in GABA interneurons. Hence, Costa suggests that schizophrenia includes GABAergic neuron morbidity which probably should be treated with nonsedative benzodiazepines, such as imidazenil. In collaboration with Dr. Guidotti, he has shown that this drug positively and allosterically modulates GABA action at GABAA receptors without causing sedation. Imidazenil fails to elicit sedation because it selectively modulates GABAA receptors that include a5 subunits. In collaboration with Dr. Guidotti, they discovered that the molecular pathology of schizophrenia includes a deficit in GABAergic interneuron function characterized by a downregulation of GAD67 and reelin. The latter protein is selectively synthesized in the cortex by GABAergic neurons. Probably, reelin is operative in event-related neuronal protein synthesis which occurs in pyramidal neurons in the proximity of dendritic spines.

Guiding principles and significant discoveries

The schizophrenic brain