Richard Maddock

Richard Maddock, M.D.
Professor of Psychiatry and Behavioral Sciences
916-734-3286
rjmaddock@ucdavis.edu

1982 - M.D. - University of California, Davis
1975 - M.S. - University of California, Davis - Physiology
1970 - B.A. - University of California, Davis - Psychology

The metabolic infrastructure of the brain is inseparable from its information processing activities. The most general hypothesis that guides research in my laboratory is that brain metabolic dysfunction has an important and under-appreciated role in the pathogenesis of psychiatric disorders. Current studies are focused on constraining and testing models in which disturbances of brain metabolism have a causal role in anxiety disorders, mood disorders and psychotic disorders. We use resting state and dynamic magnetic resonance spectroscopy (MRS) to examine the possible pathogenic role of metabolic disturbances in a variety of psychiatric disorders. Neural activation can lead to changes in brain lactate, pH, glutamate, and GABA metabolism. The lactate and glutamate changes are abnormal in patients with Panic Disorder. Physical exercise produces a unique brain state that is associated with dramatic increases in non-oxidative metabolism of glucose. This appears to be associated with increased production and clearance of brain lactate and increased de novo synthesis of brain glutamate and GABA. Understanding these brain metabolic adaptations to physical activity may improve our ability to develop therapeutically effective exercise prescriptions for individual patients with psychiatric disorders.

Ongoing studies examine disturbances in the metabolic infrastructure of the brain in schizophrenia and related conditions. Neuropathological evidence and current circuit models predict a key role for abnormal brain GABA metabolism in psychotic disorders. MRS measures of cortical GABA consistently predict cognitive performance in healthy subjects, but this relationship may be abnormal in schizophrenia. Growing evidence also implicates a role for neuroimmune mechanisms in the developmental pathogenesis of schizophrenia and other neurodevelopmental disorders. My laboratory is using MRS measures of glutathione and other brain metabolites as part of the UC Davis Conte Center studies of neuroimmune mechanisms in psychiatric disorders.

Smucny J, Carter CS, Maddock RJ. Medial Prefrontal Cortex Glutamate is Reduced in Schizophrenia and Moderated by Measurement Quality: A Meta-analysis of 1H-MRS Studies. Biological Psychiatry, 2021, 90(9):643-651. doi: 10.1016/j.biopsych.2021.06.008

Hui SCN, Mikkelsen M, Zöllner HJ, and 132 others, including Maddock, RJ. Frequency drift in MR spectroscopy at 3T. NeuroImage, 2021, 241:118430. doi: 10.1016/j.neuroimage.2021.118430

Smucny J, Carter CS, Maddock RJ. Magnetic resonance spectroscopic evidence of increased choline in the dorsolateral prefrontal and visual cortices in recent onset schizophrenia. Neuroscience Letters, Dec 2021. doi: 10.1016/j.neulet.2021.136410

Yang YS, Maddock RJ, Zhang H, Lee J, Hellemann G, Marder SR, Green MF. N-Acetylcysteine effects on glutathione and glutamate in schizophrenia: A preliminary MRS study. Psychiatry Res Neuroimaging. 2022 Sep;325:111515. Epub 2022 Jun 23. doi: 10.1016/j.pscychresns.2022.111515

Ragland, JD, Maddock RJ, Hurtado M, Tanase C, Lesh TA, Niendam TA, Carter CS Ranganath, C. Disrupted GABAergic Facilitation of Working Memory Performance in People with Schizophrenia. Neuroimage: Clinical, 2020;25:102127. doi: 10.1016/j.nicl.2019.102127

Yoon JH, Maddock RJ, DongBo Cui E, Minzenberg MJ, Niendam TA, Lesh T, Solomon M, Ragland JD, Carter C. Reduced in vivo visual cortex GABA in schizophrenia, a replication in a recent onset sample. Schizophr Res. 2019 Nov 6. doi: 10.1016/j.schres.2019.10.025

Lesh TA, Maddock RJ, Howell A, Wang H, Tanase C, Daniel Ragland J, Niendam TA, Carter CS. Extracellular free water and glutathione in first-episode psychosis-a multimodal investigation of an inflammatory model for psychosis. Molecular Psychiatry, 2019 May 28. doi: 10.1038/s41380-019-0428-y

Maddock, R.J., Caton, M.D., Ragland, J.D. Estimating glutamate and Glx from GABA-optimized MEGA-PRESS: Off-resonance but not difference spectra values correspond to PRESS values. Psychiatry Research Neuroimaging, 279:22-30, 2018. doi: 10.1016/j.pscychresns.2018.07.003

Javitt DC, Carter CS, Krystal JH, Kantrowitz JT, Girgis RR, Kegeles LS, Ragland JD, Maddock RJ, Lesh TA, Tanase C, Corlett PR, Rothman DL, Mason G, Qiu M, Robinson J, Potter WZ, Carlson M, Wall MM, Choo TH, Grinband J, Lieberman JA. Utility of Imaging-Based Biomarkers for Glutamate-Targeted Drug Development in Psychotic Disorders: A Randomized Clinical Trial. JAMA Psychiatry, 75(1):11-19, 2018. link

Greenhouse, I., King, M., Noah, S., Maddock, R.J., Ivry, R.B. Individual differences in resting corticospinal excitability are correlated with reaction time and GABA content in motor cortex. Journal of Neuroscience, 37(10):2686-2696, 2017. link

Yoon, J.H., Grandelis, A., Maddock, R.J. Dorsolateral prefrontal cortex GABA concentration in humans predicts working memory load processing capacity. Journal of Neuroscience, 36(46):11788–94, 2016. link

Greenhouse, I., Noah, S., Maddock, R.J., Ivry, R.B. Individual differences in GABA content are reliable but are not uniform across the human cortex. NeuroImage, 139:1-7, 2016. link

Maddock, R.J., Casazza, G.A., Fernandez, D.H., and Maddock, M.I. Acute Modulation of Cortical Glutamate and GABA Content by Physical Activity. Journal of Neuroscience, 36(8):2449-57, 2016. link

Buonocore, M.H. and Maddock, R.J. Magnetic resonance spectroscopy of the brain: A review of physical principles and technical methods. Reviews in the Neurosciences, 26(6):609-32, 2015. link

Maddock, R.J. The problem of spurious correlation between pairs of brain metabolite values measured in the same voxel with MRS. JAMA Psychiatry, 71:338-9, 2014. link

Maddock, R.J., Buonocore, M.H., Miller, A.R., Yoon, J.H., Soosman, S.K., Unruh, A.M. Abnormal activity-dependent brain lactate and glutamate+glutamine responses in panic disorder. Biological Psychiatry, 73(11): 1111-1119, 2013. link

Maddock, R.J., Buonocore, M.H. MR spectroscopic studies of the brain in psychiatric disorders. Current Topics in Behavioral Neuroscience, 1 Jan 2012, 11:199-251. link

Maddock, R.J., Casazza, G.A., Buonocore, M.H., Tanase, C. Vigorous exercise increases brain lactate and Glx (glutamate+glutamine): A dynamic 1H-MRS study. NeuroImage, 2011; 57(4): 1324-1330. link

Esquivel, G., Schruers, K.R., Maddock, R.J., Colasanti, A., Griez, E.J. Acids in the brain: A factor in panic? Journal of Psychopharmacology, 24:639-47, 2010. link

Yoon, J.H., Maddock, R.J., Rokem, A.S., Silver, M.A., Minzenberg, M.J., Ragland, J.D., Carter, C.S. GABA concentration is reduced in visual cortex in schizophrenia and correlates with orientation-specific surround suppression. Journal of Neuroscience, 30:3777-81, 2010. link

Maddock, R.J., Frein, S.T. Reduced memory for the spatial and temporal context of unpleasant words. Cognition and Emotion, 23:96-117, 2009. link

Maddock, R.J., Buonocore, M.H., Copeland, L.E., Richards, A.L. Elevated brain lactate responses to neural activation in panic disorder: A dynamic 1H-MRS study. Molecular Psychiatry, 14: 537-545, 2009. link

Maddock RJ, Buonocore MH. Measuring Brain Lactate at Rest and during Visual Stimulation: Reply to Sijens and Oudkerk. Psychiatry Research Neuroimaging, 162:175-179, 2008.

Garrett AS, Maddock RJ. Separating subjective emotion from the perception of emotion-inducing stimuli: An fMRI study. NeuroImage, 33:263-74, 2006. link

Maddock RJ, Buonocore MH, Lavoie SP, Copeland LE, Kile SJ, Richards AL, Ryan JM (2006). Brain lactate responses during visual stimulation in fasting and hyperglycemic subjects: A proton magnetic resonance spectroscopy study at 1.5 Tesla. Psychiatry Research: Neuroimaging, 148:47-54. link

Maddock, R.J., Buonocore, M.H., Kile, S.J., Garrett, A.S. (2003). Brain regions showing increased activation by threat-related words in panic disorder. Neuroreport, 14:325-8. link

Maddock, RJ, Garrett, AS and Buonocore MH (2003). Posterior cingulate cortex activation by emotional words: fMRI evidence from a valence decision task. Human Brain Mapping, 18(1):30-41. link | set of 256 matched emotional and neutral words

Rita Hargrave, Richard J. Maddock, Valerie Stone (2002). Impaired recognition of facial expressions of emotion in Alzheimer's disease. Journal of Neuropsychiatry and Clinical Neuroscience, 14(1):64-71. link

Garrett, A.S., Maddock, R.J. (2001). Time course of the subjective emotional response to aversive pictures: relevance to fMRI studies. Psychiatry Research: Neuroimaging, 108:39-48. link

Maddock, RJ, Garrett, AS and Buonocore MH (2001). Remembering familiar people: the posterior cingulate cortex and autobiographical memory retrieval. Neuroscience, 104(3):667-76. link

Richard J. Maddock (2001). The lactic acid response to alkalosis in panic disorder: an integrative review. Journal of Neuropsychiatry and Clinical Neurosciences, 13(1):22-34. link

Maddock RJ. (1999). The retrosplenial cortex and emotion: new insights from functional neuroimaging of the human brain. Trends in Neurosciences, 22:310-316. link