David Lewis, MD

  • Chair, Department of Psychiatry
  • Distinguished Professor of Psychiatry and Neuroscience
  • Thomas Detre Professor of Academic Psychiatry

Education & Training

  • Medical School – Ohio State University – MD
  • Residency – University of Iowa – Internal Medicine & Psychiatry
  • Post-Doctoral – Scripps Clinic & Research Foundation - Neuroscience

Research Grants

NIH Grants:  R01, P50

Research Summary

Dr. Lewis’ research activities focus on the neural circuitry of the prefrontal cortex and related brain regions, and the alterations of this circuitry in schizophrenia. The research strategy underlying these investigations involves several components. First, the normal functional architecture of the primate prefrontal cortex, including its connections with other cortical and subcortical regions, is examined using the macaque monkey as a model system for the human brain. Within these circuits, the expression and cellular localization of specific gene products, and how these change in an activity-dependent fashion, are investigated. The electrophysiological properties of intrinsic prefrontal cortical circuits are studied using an in vitro slice preparation. Second, the postnatal development of primate prefrontal cortical circuitry is characterized, with special emphasis placed on maturational events, such as synaptic pruning, which occur during adolescence. The timing and specificity of these processes are examined for their possible contribution to the emergence and refinement of the types of cognitive abilities that are disturbed in schizophrenia. Third, based on the results of these lines of investigation, hypotheses are generated regarding the elements of neural circuitry that are dysfunctional in schizophrenia. These hypotheses are then tested in postmortem human brain specimens from subjects with schizophrenia. Fourth, the primate model system is used to assess the influence of psychotropic medications on the neural circuits of interest. Fifth, mouse genetic models are used as “proof of concept” tests of the cause-effect relationships among the neural circuitry alterations observed in schizophrenia. The goal of these studies is to define the pathogenic mechanisms and pathophysiological processes that give rise to the cognitive deficits of schizophrenia. These findings are used to identify potential targets for novel therapeutic interventions that are examined in Phase II clinical trials. Dr. Lewis has served as a mentor to over 60 graduate students, post-doctoral fellows and junior faculty (including NIMH K awardees), currently directs an NIMH-funded research training program for under-represented minority and disadvantaged undergraduates, and has participated as a mentor to young investigators at multiple national meetings, including the American College of Neuropsychopharmacology, American Psychiatric Association and Society for Biological Psychiatry. Dr. Lewis has also served on advisory boards for multiple training grants.

Representative Publications

  1. Hoftman G, Dienel S, Bazmi H, Zhang Y, Chen K, Lewis DA: Altered gradients of glutamate and GABA transcripts in the cortical visuospatial working memory network in schizophrenia. Biol Psychiatry 83:670-679, 2018.
  2. Enwright JF, Huo Z, Arion D, Corradi JP, Tseng G, Lewis DA: Transcriptome alterations of prefrontal cortical parvalbumin neurons in schizophrenia. Mol Psychiatry 23:1606-1613, 2018.
  3. Arion D, Huo Z, Enwright JF, Corradi JP, Tseng G, Lewis DA: Transcriptome alterations in prefrontal pyramidal neurons distinguish schizophrenia from bipolar and major depressive disorders. Biol Psychiatry 82:594-600, 2017.
  4. Datta D, Arion D, Roman KM, Volk DW, Lewis DA: Altered expression of ARP2/3 complex signaling pathway genes in prefrontal layer 3 pyramidal cells in schizophrenia. Am J Psychiatry 174:163-171, 2017
  5. Chung W, Wills ZP, Fish KN, Lewis DA: Developmental pruning of excitatory synaptic inputs to parvalbumin interneurons in monkey prefrontal cortex. Proc Natl Acad Sci USA 114:E629-E637, 2017
  6. Kimoto S, Zaki MM, Bazmi HH, Lewis DA: Altered markers of cortical Gamma-aminobutyric acid neuronal activity in schizophrenia: Role of the NARP gene. JAMA Psychiatry 72:747-756, 2015