Erminio Costa, M.D.
Scientific Director, Psychiatric Institute
Professor of Biochemistry in Psychaitry
Phone: (312) 413-4591
E-mail: Costa@psych.uic.edu

Dr. Erminio Costa has contributed to the initial development of the psychopharmacology of  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 modulate 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 5 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.

Biosketch:

• July, 1947 M.D. 110/110 cum laude, University of Cagliari, Italy
• 1950-1960 Thudichum Psychiatric Research Laboratory, Galesburg Research Hospital, Galesburg, Illinois
• 1960-1965 Deputy Chief, Laboratory Chemical Pharmacology at NHLI - NIH, Bethesda, Maryland
• 1965-1968 Associate Professor of Pharmacology and Neurology, College of Physicians and Surgeons of Columbia University, New York, NY
• 1968-1985 Chief, Laboratory Preclinical Pharmacology, NIMH, St. Elizabeth Hospital, Washington, DC
• 1985-1994 Director and Founder, Institute of Neuroscience, and Professor of Pharmacology, Georgetown University, Washington, DC
• 1994-1995 Director, Center for Neuropharmacology, Nathan S. Kline Institute, New York University, New York, NY
• 1995-present Scientific Director, Psychiatric Institute, Professor of Biochemistry in Psychiatry, Department of Psychiatry, College of Medicine, University of Illinois at Chicago, Chicago, Illinois
• 1982 Member, National Academy of Sciences 
• 1991 Member of "Academia dei Lincei" founded by Galileo Galilei in 1602, Rome

Recent Publications

• 1997 Impagnatiello F, Oberto A, Longone P, Costa E, and Guidotti A: 7-Chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine S,S-dioxide: A partial modulator of AMPA receptor desensitization devoid of neurotoxicity. PNAS ; 1997; 94:7053-7058.
• 1998 Costa E: From GABA_A receptor diversity emerges a unified vision of GABAergic inhibition. Annu Rev Pharmacol Toxicol. 1998  38:321-350.
• 1998 Giorgetti M, Davis E, Costa E, Guidotti A, Appel SB, Brodie MS: Imidazenil, a positive allosteric GABA_A receptor modulator, inhibits cocaine's effects on locomotor activity and extracellular dopamine in the nucleus accumbens shell without tolerance liability. JPET (in press)
• 1998 Pesold C, Impagnatiello F, Pisu MG, Uzunov DP, Costa E, Guidotti A, and Caruncho HJ: Reelin is preferentially expressed in neurons synthesizing gamma-aminobutyric acid (GABA) in cortex and hippocampus of adult rats. PNAS 95:3221-3226, 1998.
• 1998 Uzunova V, Sheline Y, Davis JM, Rasmusson A, Uzunov DP, Costa E, and Guidotti A: Increase in the cerebrospinal fluid content of neurosteroids in patients with unipolar major depression who are receiving fluoxetine or fluvoxamine. PNAS 95: 3239-3244, 1998.
• 1998 Guidotti A and Costa E: Can the antidysphoric and anxiolytic profiles of SSRIs be related to their ability to increase brain 3-alpha,5alpha-tetrahydroprogesterone (ALLO) availability? Biol Psych (in press).