Mark A. Geyer, Ph.D.
Distinguished Professor Emeritus of Psychiatry and Neurosciences
Vice-Chair for Scientific Affairs in Psychiatry
T: (619) 543-3582
F: (619) 543-2493
Mark A. Geyer Ph.D. is the former Vice Chair for Research in Psychiatry and directs the Neuropsychopharmacology Unit of the VISN 22 VA’s Mental Illness Research, Clinical, and Education Center. He was involved intensively in the NIMH-funded MATRICS, TURNS, and CNTRICS Programs. Dr. Geyer is a pioneer in the translational study of sensorimotor gating deficits in schizophrenia and related animal models and has published over 425 peer-reviewed papers and many reviews, chapters, and edited books. He is the lead Series Editor for Current Topics in Behavioral Neurosciences, which has completed 16 volumes. His research program has been supported continuously by grants from NIMH and NIDA for 30+ years. He is Associate Editor of Neuropsychopharmacology, Fellow and Council Member of the ACNP, Fellow of AAAS and American Psychological Society, Past-President of the Serotonin Club, Past-President and Fellow of International Behavioral Neuroscience Society, member of Scientific Council of NARSAD, Scientific Advisor to European Union’s Innovative Medicine Initiative, and 2011 awardee of Bleuler Prize for Research in the Schizophrenias.
Description: Tanslational research in psychiatry neuroscience
Dr. Geyer’s research group focuses on developing parallel behavioral paradigms in animals and humans for use in psychiatric drug discovery. For example, working with Dr. David Braff, Dr. Geyer published the first study demonstrating that prepulse inhibition (PPI) of startle, a measure of sensorimotor gating, is disrupted in schizophrenic patients in 1978. Since then, research in his laboratory has shown that PPI in animals is disrupted by a number of agents that are psychoactive in humans and in a number of lines of mutant mice. These findings led to the acceptance of PPI as an animal model related to schizophrenia and bipolar mania that reflects aspects of the disease states observed in patients. His translational group currently includes five faculty members, Drs. Susan Powell, Victoria Risbrough, Xianjin Zhou, Jared Young, and Adam Halberstadt. Our combined laboratories use behavioral measures and psychopharmacological manipulations in rodents and humans to examine the roles of neurotransmitters in behavior, to develop animal models of human drug effects, and to explore information-processing deficits in psychiatric disorders. We use startle measures of habituation, prepulse inhibition, anxiety potentiation, and fear extinction that are deficient in psychiatric disorders and can be mimicked in rodents by pharmacological, developmental, and genetic manipulations. Under Dr. Risbrough’s leadership, the group is using a battery of startle tests in a prospective longitudinal Marine Resilience Study, paralleled by neurobiological studies of CRF systems and stressors in rodents. Dr. Geyer has developed a Behavioral Pattern Monitor for use in rats, mice, and humans. These systems provide cross-species translational and multivariate assessments of spatio-temporal patterns of exploratory behavior and are being used in comparisons of schizophrenia and bipolar mania in relationship to corresponding animal models and the effects of psychostimulants in human volunteers. We have explored the effects of classical hallucinogens, dopaminergic psychostimulants, and both direct and indirect serotonin agonists to elucidate their respective mechanisms of action and to reveal the involvement of specific monoamine systems and receptors in behavioral responses to environmental stimuli and in processes such as arousal, habituation, and sensorimotor gating. Animal models of interest in the laboratory include pharmacological manipulations, a variety of developmental perturbations, and genetic models involving strain comparisons, knockouts, and humanized mutant mice, most of which are related to psychotic and/or stress-related disorders. A current focus of the laboratory is the development of murine tests of specific cognitive domains relevant to the MATRICS and CNTRICS efforts to treat cognitive deficits in psychiatric disorders.
- Geyer MA, Krebs-Thomson K, Braff DL, Swerdlow NR (2001) Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: A decade in review. Psychopharmacology 156:117-154
- Geyer MA, McIlwain KL, Paylor R (2002) Mouse genetic models for prepulse inhibition: An early review. Molecular Psychiatry 7:1039-1053
- Geyer MA and Vollenweider FX (2008) Serotonin research: Contributions to understanding psychoses. Trends in Pharmacological Sciences, 29:445-453.
- Geyer MA. (2008) Developing translational animal models for symptoms of schizophrenia or bipolar mania. Neurotoxicity Research, 14:71-78.
- Young JW, Powell S, Risbrough VB, Marston HM, Geyer MA (2009) Using the MATRICS to guide development of a preclinical cognitive test battery for research in schizophrenia. Pharmacology and Therapeutics. 122:150–202.
- Risbrough VB, Geyer MA, Hauger RL, Coste S, Stenzel-Poore M, Wurst W, Holsboer F. (2009) CRF1 and CRF2 receptors required for potentiated startle to contextual but not discrete cues. Neuropsychopharmacology, 34:1494-503.
- Young, J.W., Light, G.A., Marston, H.M., Sharp, R., Geyer, M.A.: The 5-choice continuous performance test: Evidence for a translational test of vigilance test for mice. PLoS ONE, 4(1):e4227, 2009. PMCID2626630
- Perry W, Minassian A, Paulus MP, Young JW, Kincaid M, Ferguson E, Henry BL, Zhuang X, Masten VL, Sharp RF, Geyer MA. (2009) A reverse-translational study of dysfunctional exploration in psychiatric disorders: From Mice to Men. Archives of General Psychiatry, 66:1072-1080.
- Zhou X, Nie Z, Roberts A, Zhang D, Sebat J, Malhotra D, Kelsoe JR, Geyer MA (2010) Reduced NMDAR1 expression in the Sp4 hypomorphic mouse may contribute to endophenotypes of human psychiatric disorders. Human Molecular Genetics, 19:3797-3805.
- Geyer MA. (2010) New opportunities in the treatment of cognitive impairments associated with schizophrenia. Current Directions in Psychological Sciences, 19:264-269.
- Zhou, X., Chen, Q., Schaukowitch, K., Kelsoe, J.R., and Geyer, M.A. (2010) Insoluble DISC1-Boymaw fusion proteins generated by the DISC1 translocation. Molecular Psychiatry, 15:669-672. doi:10.1038/mp.2009.127; PMCID: PMC2891102
- Geyer MA, Olivier B, Joëls M, Kahn R (2012) From antipsychotic to anti-schizophrenia drugs: Role of animal models. Trends in Pharmacological Sciences, 33:515-521. PMCID3461097.
- Geyer, M.A. and Gross, G. (eds.), Novel Antischizophrenia Treatments, HANDBOOK OF EXPERIMENTAL PHARMACOLOGY, Volume 213, Springer-Verlag Berlin Heidelberg, 455 pp., 2012.
- Powell, S.B., Weber, M., and Geyer, M.A. (2012) Genetic models of sensorimotor gating: Relevance to neuropsychiatric disorders. Current Topics in Behavioral Neuroscience, 12:251-318, 2012. PMC3357439
- Halberstadt, A.L. and Geyer, M.A. (2013) Serotonergic hallucinogens as translational models relevant to schizophrenia. The International Journal of Neuropsychopharmacology, 16:2165-2180.