Professor John M Davis Named the 2025 Lifetime Achievement Awardee
Dr. John M Davis is professor of psychiatry at the University of IL at Chicago. He began his career as a clinical associate at NIH, and, with William Bunney, reviewed evidence that biogenic amines may be decreased in depression, which was published one month after Dr. Schildkraut’s seminal paper. Dr. Davis, in collaboration with Steve Curry, did the first studies of antipsychotic plasma levels in man (1969), showing plasma levels are associated with side effects. They found much higher plasma levels after intramuscular administration than oral administration, an elucidation of first-pass metabolism, where oral medication is extensively metabolized in its first pass through the liver. Davis also described several drug-drug interactions.
Dr. Davis, in 1970, moved to Central State Hospital which was affiliated with Vanderbilt University. In that year, Snyder and Seeman suggested the dopamine theory of schizophrenia. Davis, working with David Janowsky, reasoned that if dopamine synthesis or release was elevated in schizophrenia, then schizophrenics might be supersensitive to a small intravenous dose of amphetamine or methylphenidate. They found that an i.v. dose that produces just noticeable euphoria in normal controls will markedly exacerbate psychosis for about 30 minutes, supports the dopamine theory. Intravenous amphetamine is used in PET imaging to estimate dopamine synthesis and release. Davis and colleagues also showed that increasing acetylcholine (by Physostigmine) reduced the worsening of psychosis produced by methylphenidate, implying an antipsychotic effect of acetylcholine.
Dr. Davis, in 1973, moved to the Illinois State Psychiatric Institute affiliated with the University of Chicago. Davis, with Tamminga and Smith, showed that a small dose of apomorphine (a dopamine partial agonist) reduced the intensity of schizophrenic symptoms. There are now several dopamine partial agonists on the market. Davis, working with Fischman and Schuster, found that after iv or im administration, cocaine plasma levels generally paralleled the subjective effect, but the subjective effects of cocaine decreased more rapidly than did the plasma level. When an additional administration of cocaine was given an hour later, it produced little physiological response suggesting there was a rapid development of tolerance.
Dr. Davis, in 1986 moved to the University of IL at Chicago. Drs. Costa, Guidotti, Grayson and Davis found increased levels of DNA methyltransferase (DNMT) in the same postmortem brains with decreased reelin/GAD67 in comparison to normal controls, suggesting that increased methylation silenced the reelin and GAD67 gene. They suggested that low levels of reelin and GAD67mRNA and protein expression may play a role in the pathophysiology of schizophrenia. This was one of the first epigenetic studies in psychiatry.
A Message from John M Davis
A letter from Robert C. Smith on John M Davis
John Davis has made many original contributions to schizophrenia research and treatment over a course of a 55 year career which qualify him for the lifetime achievement award from SIRS. These include: a) translational clinical research, b) developing the foundation of meta-analysis in psychiatry, c) teaching and popularizing scientific evidence in clinical psychopharmacology for the treatment of schizophrenia and other psychiatric disorders, and d) training and mentoring many of the psychiatric researchers and clinicians both in the U.S. and other countries. John Davis was Director of Research at the Illinois Psychiatric Institute and Gilman Professor of Psychiatry for over 20 years, where he directed multiple research studies related to schizophrenia and also helped train a large cadre of psychiatric researchers both in the US and China who have made their own important contributions to the field. His major research has been in the field of schizophrenia and antipsychotic drugs, but has extended to other psychiatric disorders.
Major Research, Mentoring and Clinical Contributions
1) John was first person to bring meta-analysis into studies of psychiatry and studies of antipsychotic drugs, even before the term meta-analysis was coined and has published multiple meta-analysis studies of psychiatric drugs in leading journals (Arch Gen Psychiatry, Lancet, and Am. Journal Psychiatry).
2) With Robert Gibbons he introduced Mixed Model analysis and Mixture Distribution analysis into clinical psychiatric research which has become standard in studies of many psychiatric drug trials in schizophrenia.
3) He did research helping translate the basic science work of Arvid Carlson on effects of partial dopamine agonists into clinical studies of the effects of apomorphine on schizophrenic's symptoms and tardive dyskinesia, which was published in Science and other leading journals.
4) He translated the chemical assays developed for measurement of psychiatric drugs by fluorescence and gas-liquid chromatography (from Curry's lab at NIH) to clinical studies of the relationship of blood levels of antipsychotic drugs and clinical response, established many drug-drug interactions, and developed therapeutic window concept in this research area.
5) Helped develop research in China on Sulforaphane as an adjunctive treatment for schizophrenia.
6) He devised clinical experiments translating the dopaminergic theory of schizophrenia into clinical studies showing that small IV doses of methylphenidate and amphetamines worsen symptoms of schizophrenia (with David Janowsky).
7) He had an important role in translating of basic research on methylation related epigenetic abnormalities involved in producing the GABAergic deficits in schizophrenia (DNMT1, TET, GAD67, REELIN) from mouse animal models, to post-mortem brain samples of schizophrenics and controls, and then to studies of these abnormalities in lymphocytes of living schizophrenics, with papers published in PNAS, Schizophrenia Research and other journals. This lead to an NIH grant to study epigenetics of schizophrenia in US and China.
8) John has trained many researchers and clinical psychopharmacologists, both in the U.S. and China countries, who have gone on to productive independent careers in which they have made important contributions to schizophrenia research and other areas of psychiatry and become leaders in the field. These include: David Janowsky Carol Tamminga, David Garver, Robert Smith, Regina Caspar, Ghanshyam Pandey, Stefan Leucht, Robert Gibbons, Joseph Hibbeln. Minguan Zhang, Hua Jin, Chunbo Li, and many other psychiatric researchers (full list in his attached cv).
9) John has authored or co-authored multiple books, chapters, and papers bringing the science of psychopharmacology to address evidence based strategies for the drug treatment of schizophrenia and other mental disorders, and teaching clinicians about the appropriate psychopharmacological treatment of psychiatric disease. including The Diagnosis and Treatment of Psychiatric Disorders (several editions), chapter’s in Comprehensive Textbook of Psychiatry and several other books.
These multiple areas of lifetime achievements make John Davis one of the leading schizophrenia and psychopharmacology researchers of the past 55 years and an ideal candidate for the SIRS Lifetime Achievement Award.
Sincerely
Robert C. Smith, M.D., PhD.
Research Professor of Psychiatry, NYU Medical School
Research Psychiatrist, Nathan Kline Institute for Psychiatric Research
