THE SAVITZ LABORATORY
Jonathan Savitz, Ph.D.Principal Investigator, Laureate Institute for Brain Research
Associate Professor, Oxley College of Health Sciences, The University of Tulsa Volunteer Faculty Member, Department of Psychiatry, University of Oklahoma Curriculum Vitae Google Scholar Profile Email: jsavitz@laureateinstitute.org | Phone: 918-502-5104
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(1). Just as a cardiac stress test can be used to identify abnormalities of the heart that are not visible at rest, so to can “stressing” the immune system enable us to detect hidden factors that may lead to maladaptive immune responses. We use low-dose endotoxin, part of the cell wall of gram-negative bacteria, to “trick” the immune system into launching a transient inflammatory response. To our knowledge, we are the first group in the world to perform an endotoxin challenge on depressed volunteers. Knowledge gained from this study will help us understand the mechanisms through which an inflammatory stimulus alters brain activity in a way that makes some people vulnerable to developing depression in the setting of inflammation.
(2). Herpesvirus infections in healthy adults were traditionally considered to be harmless but there is emerging evidence that these viruses may not be completely benign. Herpesviruses lie dormant until they are reactivated by physical or psychological stressors. Conceivably, this periodic viral replication may trigger inflammatory responses that lead to depression. We are testing this hypothesis by following volunteers over the course of several months in order to evaluate whether fluctuations in stress and mood co-occur with changes in viral activity. This research may lead to the initiation of a clinical trial to test whether anti-viral agents have therapeutic benefits in depression.
(3). The balance of kynurenine pathway metabolism has been shown to be altered in depression such that an excess of neurotoxic kynurenines is produced. These metabolites damage neuronal cells and impair synaptic plasticity (changes in the junctions between neurons that allow them to communicate). Real time neurofeedback of the amygdala is a promising treatment for depression that likely works in part by altering the connections between neuronal cells. This study tests whether people with higher levels of neurotoxic kynurenine metabolites will be less likely to respond to neurofeedback. The research may help us develop a blood biomarker to determine who should receive this type of treatment.
(2). Herpesvirus infections in healthy adults were traditionally considered to be harmless but there is emerging evidence that these viruses may not be completely benign. Herpesviruses lie dormant until they are reactivated by physical or psychological stressors. Conceivably, this periodic viral replication may trigger inflammatory responses that lead to depression. We are testing this hypothesis by following volunteers over the course of several months in order to evaluate whether fluctuations in stress and mood co-occur with changes in viral activity. This research may lead to the initiation of a clinical trial to test whether anti-viral agents have therapeutic benefits in depression.
(3). The balance of kynurenine pathway metabolism has been shown to be altered in depression such that an excess of neurotoxic kynurenines is produced. These metabolites damage neuronal cells and impair synaptic plasticity (changes in the junctions between neurons that allow them to communicate). Real time neurofeedback of the amygdala is a promising treatment for depression that likely works in part by altering the connections between neuronal cells. This study tests whether people with higher levels of neurotoxic kynurenine metabolites will be less likely to respond to neurofeedback. The research may help us develop a blood biomarker to determine who should receive this type of treatment.
Scientific Background
Dr. Savitz received an undergraduate degree (B.S.) in psychology and genetics from the University of the Witwatersrand in Johannesburg, performed further graduate work in neuropsychology, including a clinical internship, and then completed a PhD on the genetics of bipolar disorder at the University of Cape Town in 2006. He subsequently completed a post-doctoral fellowship at the National Institutes of Health and is currently a Principal Investigator at the Laureate Institute for Brain Research and an Associate Professor at The University of Tulsa. Jonathan has trained with two of the most well-known experts in their respective fields: Wayne Drevets (mood disorders, neuroimaging) and Robert Dantzer (psychoneuroimmunology), and has conducted a number of innovative studies that have addressed important gaps in our knowledge regarding the relationship between genes, immunological function, and neuroimaging abnormalities in mood disorders. Dr. Savitz has published over 60 first or senior author scientific papers and has been the PI on three NIH grants. He is an associate editor of the journal, Neuroscience Letters and is an editorial board member of Brain, Behavior, and Immunity and Heliyon. He has served as a reviewer for numerous European and American grant agencies, including the MESH study section of the NIH.
Lab Members
Leandra Figueroa-Hall, Ph.D.
Post-Doctoral Research Associate |
Soumyabrata Munshi
Post-Doctoral Research Associate |
MacGregor Thomas
Research Specialist |
Haixia Zheng, Ph.D.
Associate Investigator |
Selected Publications
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Savitz, J. (2020). The Kynurenine Pathway: A Finger in Every Pie. Molecular Psychiatry. 25(1):131-147.
Savitz J, Teague T.K., Misaki M., Macaluso M., Wurfel B.E., Meyer M., Drevets D., Yates W., Gleason O., Drevets W.C., Preskorn S.H. (2018). Treatment of Bipolar Depression with Minocycline and/or Aspirin: An adaptive, 2 X 2 double-blind, randomized, placebo-controlled, phase IIA clinical trial. Translational Psychiatry. 8, e27.
Mechawar, N. and Savitz, J. (2016). Neuropathology of Mood Disorders: Do we see the stigmata of inflammation? Translational Psychiatry. 6, e946.
Savitz, J.B., Rauch, S. L., Drevets, W.C. (2013). Clinical Application of Brain Imaging for the Diagnosis of Mood Disorders: The current state of play. Molecular Psychiatry. 18, 528-539.
Savitz, J.B., Nugent, A.C., Bogers, W., Roiser, J.P., Bain, E.E., Neumeister, A., Zarate, Jr., C.A., Manji, H.K., Cannon, D.M., Marrett, S., Henn, F., Charney, D.S., Drevets, W.C. (2011). Habenula Volume in Bipolar Disorder and Major Depressive Disorder: A High Resolution MRI Study. Biological Psychiatry. 69, 336-343.
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Ford, B.N., Yolken, R.H., Aupperle, R.L., Teague, T.K., Irwin, M.R., Paulus, M.P., Savitz, J. (2019). Association of Early-Life Stress with Cytomegalovirus Infection in Adults with Major Depressive Disorder. JAMA Psychiatry. 76(5):545-547.
Ford, B.N., Yolken, R.H., Dickerson, F.B., Teague, T.K., Irwin, M.R., Paulus, M.P., Savitz, J. (2019). Reduced Immunity to Measles in Adults with Major Depressive Disorder. Psychological Medicine. 49, 243-249.
Wurfel, B.E., Drevets, W.C., Bliss, S.A., McMillin, J.R., Suzuki, H., Ford, B.N., Morris, H.M., Teague, T.K., Dantzer, R., Savitz, J. (2017). Serum Kynurenic Acid is Reduced in Affective Psychosis. Translational Psychiatry. 7, e1115.
Savitz, J., Drevets, W.C., Smith, C.M., Victor, T.A., Wurfel, B.E., Bellgowan, P.S.F., Bodurka, J., Teague, T.K., Dantzer, R. (2015). Putative Neuroprotective and Neurotoxic Kynurenine Pathway Metabolites are Associated with Hippocampal and Amygdalar Volumes in Subjects with Major Depressive Disorder. Neuropsychopharmacology. 40, 463-471.
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Research Collaborators
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Jin Cho, M.D., Ph.D.
University of California- Los Angeles Robert Dantzer, Ph.D.
MD Anderson Cancer Center, University of Texas Wayne Drevets, M.D.
Janssen Pharmaceuticals, Inc. |
David Goldman, M.D.
National Institute on Alcohol Abuse and Alcoholism Mike Irwin, M.D.
University of California- Los Angeles Brett McKinney, Ph.D.
University of Tulsa |
Kent Teague, Ph.D.
University of Oklahoma- Tulsa Bob Yolken, M.D.
Johns Hopkins University |
