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Gregory A. Ordway, Ph.D.
Department of Biomedical Sciences
B.S. Pharmacy; The Ohio State University
Hui Wang-Keaton, Ph.D.
Assistant Professor, Assistant Clinical Professor; Case Western Reserve University
School of Medicine 1988-2000
Major depression, suicide and antidepressants
Our research on MAJOR DEPRESSION AND SUICIDE:
Major depression is a devastating disorder that affects millions of Americans each year. Sadly, depression is primary contributor to suicide, and over 42,000 people die by suicide each year in the U.S. since 2014 according to the CDC. Studies have shown that most people who die by suicide suffered from depression in some form, whether having major depressive disorder or depression in association with other psychiatric disorders. Unfortunately, the rates of suicide and depression are higher in southern Appalachia as compared to the rest of the U.S.
Dr. Ordway's laboratory is focused on understanding brain pathology that leads to or is associated with depression and suicide, with emphasis on translating that information to the development of improved treatments. Currently, his laboratory is investigating the biochemical and cellular consequences of depression-associated inflammation and oxidative damage on the brain, focusing on specific sets of cells in the brain that are uniquely susceptible to the deleterious effects of oxidative damage. Dr. Ordway's laboratory has access to a large collection of psychiatrically characterized human brain tissues that permit the study of cellular pathology in the brains of donors that suffered from depression and/or who have died by suicide, and in the brains of psychiatrically normal donors who died from natural causes.
Recently, Dr. Ordway’s laboratory discovered that depression is associated with elevated gene expression of an enzyme known as PARP1 in the brain. PARP1 activity is increased during inflammation and events that cause DNA damage. His laboratory partnered with the laboratory of Dr. Russ Brown, a behavioral neuroscientist at ETSU, to explore the possibility that PARP inhibitors have antidepressant activity. Using rodent behavioral models that are employed by industry and academic institutions to search for drugs with antidepressant activity, their laboratories have demonstrated that PARP inhibitors have robust antidepressant activity. Using the same rodent models, they also discovered that PARP inhibitors boost the antidepressant activity of a commonly prescribed antidepressant (fluoxetine). These findings open the door to the potential development of an entirely new class of antidepressant drugs, and hold great promise of improved treatment for depression in millions of people.
Ordway G.A., Szebeni A., Hernandez L.J., Crawford J.D., Szebeni K., Chandley M.J., Burgess K.C. Miller C., Bakkalbasi E. and Brown R.W.: Antidepressant-like actions of inhibitors of poly(ADP-ribose) polymerase in rodent models. Int. J. Neuropsychopharmacol. In press, 2017. https://academic.oup.com/ijnp/article/4061570/Antidepressant-Like-Actions-of-Inhibitors-of-Poly
Szebeni A., Szebeni K., DiPeri T.P., Johnson L.A., Stockmeier C.A., Crawford J.D., Chandley M.J., Hernandez L.J., Burgess K.C., Brown R.W. and Ordway G.A.: Elevated DNA oxidation and DNA repair enzyme expression in brain white matter in major depressive disorder. Int. J. Neuropsychopharmacol. 2016 Dec 29; PMID: 28034960.
Chandley M.J., Szebeni A., Szebeni K., Crawford J.D., Stockmeier C.A., Turecki G., Kostrzewa R.M., and Ordway G.A.: Elevated gene expression of glutamate receptors in noradrenergic neurons from the locus coeruleus in major depression. Int. J. Neuropsychopharmacology, 17:1569-1578, 2014. PMID: 24925192
Szebeni A., Szebeni K., Chandley M.J., Stockmeier C.A., and Ordway G.A.: Shortened telomere length in white matter oligodendrocytes in major depression: potential role of oxidative stress. Int. J. Neuropsychopharmacology, 17:1579-1589, 2014. PMID: 24967945.
Fan Y., Chen P., Li Y. Ordway G.A., and Zhu M.-Y.: Effects of desipramine treatment on stress-induced upregulation of norepinephrine transporter expression in rat brain. Psychopharmacology, 232:379-390, 2015. PMID: 25038868
Crawford J.D., Chandley M.J., Szebeni K., Szebeni A., Waters B. and Ordway G.A.: Elevated GFAP protein in anterior cingulate cortical white matter in males with autism spectrum disorder. Autism Res. April 6, epub ahead of print; PMID: 25846779
Chandley M.J., Crawford J.D., Szebeni A., Szebeni K. and Ordway G.A.: NTRK2 expression levels are reduced in laser captured pyramidal neurons from the anterior cingulate cortex in males with autism spectrum disorder. Molecular Autism, 6:28-39, 2015. (ahead of Pubmed)
Link to publications:
Ordway, G.A., Schwartz, M. and Frazer A.: Brain Norepinephrine: Neurobiology and Therapeutics,
Cambridge University Press, 2007.