Department of Psychiatry Faculty

Robert D. Beech, MD, PhD Assistant Professor of Psychiatry Division of Molecular Psychiatry 300 George St., 8304C Tel: 203-737-1375 Fax: 203-7371031 Email: robert.beech@yale.edu

Education

B.A., 1987, Harvard College
Ph.D., 1994, University of Illinois at Chicago
MD, 1997 University of Illinois at Chicago

Research Interest

Our laboratory is interested in the roles of transcription factors and adult neurogenesis in the neurobiology of psychiatric disorders. We are approaching this question in two related ways.

First, in the clinical arena, we are conducting microarray studies to look at changes in expression of growth factor-related genes in peripheral blood of patients being treated with antidepressant medications. Current theories regarding the mechanism of action of both mood stabilizers and antidepressants suggest that the effects of these medications are medicated by the induction of specific genes in the brain. However, the relationship of these changes to disease-state and treatment-response remains unclear because the tissue of interest (the patient's brain) is not, under normal circumstances available for study. An emerging alternative is to look for biomarkers in a surrogate tissue such as blood since the signaling pathways affected by these medications are present in a wide variety of peripheral tissues, including blood. The long-term goal of this project is to identify molecular biomarkers that are predictive of changes in mood-state and/or positive treatment-response to aid in the treatment of mood disorders including depression and bipolar disorder. Future studies will be aimed at correlating these molecular changes with clinical response to treatment and changes seen with structural and functional neuroimaging.

A second area of interest involves animal studies aimed at understanding on the role of adult neurogenesis in psychiatric disorders. Patients with major depression, bipolar disorder and schizophrenia have all been found to have decreased hippocampal volumes, suggesting that decreased hippocampal cell number may be a common endophenotype in multiple mental illnesses. Work over the past several years has also shown that chronic treatment with several classes of psychoactive medications including antidepressants, mood stabilizers and atypical antipsychotics, as well as drugs of abuse can alter neurogenesis in the adult hippocampus. Recent evidence suggests that generation of new neurons may be critical for antidepressant action. However, the functional significance of these findings and their relationship to the symptoms experienced in these various disorders remains unclear. To explore these relationships we are developing inducible-transgenic methods for expressing different genes of interest in adult generated neurons and for altering the rate of neurogenesis independently of other experimental variables. Mice with altered neurogenesis are then studied in behavioral models relevant to depression and psychosis.

Area of Expertise

Addictions Psychiatry
Molecular Neuroscience
Mouse Genetics

Laboratory Personnel

Janine Leffert, Research Assistant

Publications of Note

Beech, R.D. (2006) "Membrane-cytoskeletal interactions in the regulation of neuronal migration in the adult brain." in Progress in Stem Cell Research, Greer, E.V. ed. (Nova Science Publishers, Inc., Hauppauge, NY) (in press)

Beech, R.D., and Duman, R.S. (2005) "The role of transcription factors in the biology of depression" in Biology of Depression: Towards a Novel Understanding and Therapeutic Strategies, Licinio, J., and Wong, M.-L. eds. (Wiley-VCH, Weinheim) pp. 823-854.

Beech, R.D., Cleary, M.A., Treloar, H.B., Eisch, A.J., Harist, A.V., Zhong, W., Greer, C.A., Duman, R.S., and Picciotto,M.R. (2004) "The nestin promoter/enhancer direct transgene expression to precursors of adult generated periglomerular neurons." Journal of Comparative Neurology 475:128-141.

Caldarone, B.J., Harrist, A.V., Cleary, M.A., Beech, R.D., King, S.L., and Picciotto, M.R. (2004) "High affinity nicotinic acetylcholine receptors are required for antidepressant effects of amitriptyline cell proliferation." Biological Psychiatry 9: 657-664.

Harrist, A., Beech, R.D., King, S.L., Zanardi, A., Cleary, M.A., Caldarone, B.J., Eisch, A.J., Zoli, M., and Picciotto, M.R. (2004) "Alteration of hippocampal cell proliferation in mice lacking the ?2 subunit of the neuronal nicotinic acetylcholine receptor" Synapse 54: 200-206.

Hsu, L.-C., Liu, S., Abedinpour, F., Beech, R.D., Lahti, J.M., Kidd, V.J., Greenspan, J.A., and Yeung, C.-Y. (2003) The Murine G+C-rich promoter binding protein mGPBP is required for promoter-specific transcription" Molecular and Cellular Biology Molecular & Cellular Biology. 23(23):8773-85.

Beech, R.D. (1997) "Thyroid hormones, affective disorders, and gene regulation: a re-examination" Psychiatric Annals 27: 773-778.

Copyright © . Yale University School of Medicine, Psychiatry Department. All rights reserved.
Comments or suggestions to the site editor.

Home URL: http://info.med.yale.edu/ysm