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A References Bagni, C., and W. T. Greenough. 2005. From mRNP trafficking to spine dysmorphogenesis: The roots of Fragile X syndrome. Nat Rev Neurosci 6(5):376–387. Barch, D. M., M. G. Berman, R. Engle, J. H. Jones, J. Jonides, A. MacDonald III, D. E. Nee, T. S. Redick, and S. R. Sponheim. 2009. CNTRICS final task selection: Working memory. Schizophr Bull 35(1):136–152. Barco, A., C. H. Bailey, and E. R. Kandel. 2006. Common molecular mechanisms in explicit and implicit memory. J Neurochem 97(6):1520–1533. Bechtholt-Gompf, A. J., H. V. Walther, M. A. Adams, W. A. Carlezon, D. Öngür, and B. M. Cohen. 2010. Blockade of astrocytic glutamate uptake in rats induces signs of anhedonia and impaired spatial memory. Neuropsychopharmacology 35:2049–2059. Brennan, B. P., J. I. Hudson, J. E. Jensen, J. McCarthy, J. L. Roberts, A. P. Prescot, B. M. Cohen, H. G. Pope, Jr., P. F. Renshaw, and D. Öngür. 2010. Rapid enhancement of glu- tamatergic neurotransmission in bipolar depression following treatment with riluzole. Neuropsychopharmacology 35(3):834–846. Brown, V., P. Jin, S. Ceman, J. C. Darnell, W. T. O’Donnell, S. A. Tenenbaum, X. Jin, Y. Feng, K. D. Wilkinson, J. D. Keene, R. B. Darnell, and S. T. Warren. 2001. Microarray iden- tification of FMRP-associated brain mRNAs and altered mRNA translational profiles in fragile X syndrome. Cell 07(4):477–487. Buchanan, R., M. Davis, D. Goff, M. F. Green, R. S. Keefe, A. C. Leon, K. H. Nuechterlein, T. Laughren, R. Levin, E. Stover, W. Fenton, and S. R. Marder. 2005. A summary of the FDA–NIMH–MATRICS workshop on clinical trial design for neurocognitive drugs for schizophrenia. Schizophr Bull 31(1):5–19. Butler, P. D., V. Zemon, I. Schechter, A. M. Saperstein, M. J. Hoptman, K. O. Lim, N. Revheim, G. Silipo, and D. C. Javitt. 2005. Early-stage visual processing and cortical amplification deficits in schizophrenia. Arch Gen Psychiatry 62(5):495–504. Cairns, B. E. 2010. Pathophysiology of TMD pain—basic mechanisms and their implications for pharmacotherapy. J Oral Rehabil 37(6):391–410. 39

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40 GLUTAMATE-RELATED BIOMARKERS IN DRUG DEVELOPMENT Castrillon, E. E., B. E. Cairns, M. Ernberg, K. Wang, B. J. Sessle, L. Arendt-Nielsen, and P. Svensson. 2008. Effect of peripheral NMDA receptor blockade with ketamine on chronic myofascial pain in temporomandibular disorder patients: A randomized, double-blinded, placebo-controlled trial. J Orofac Pain 22(2):122–130. Castrillon, E. E., M. Ernberg, B. E. Cairns, K. Wang, B. J. Sessle, L. Arendt-Nielsen, and P. Svensson. 2010. Interstitial glutamate concentration is elevated in the masseter muscle of myofascial temporomandibular disorder patients. J Orofac Pain 24(4):350–360. Choi, D. W. 1994. Glutamate receptors and the induction of excitotoxic neuronal death. Prog Brain Res 100:47–51. Collingridge, G. L., J. T. Isaac, and Y. T. Wang. 2004. Receptor trafficking and synaptic plas- ticity. Nat Rev Neurosci 5(12):952–962. Cortese, B. M., and K. Luan Phan. 2005. The role of glutamate in anxiety and related disor- ders. CNS Spectrums 10(10):820–830. Doble, A. 1999. The role of excitotoxicity in neurodegenerative disease: Implications for therapy. Pharmacol Ther 81(3):163–221. Dölen, G., and M. F. Bear. 2008. Role for metabotropic glutamate receptor 5 (mGluR5) in the pathogenesis of fragile X syndrome. J Physiol 586(6):1503-1508. Eulenburg, V., and J. Gomeza. 2010. Neurotransmitter transporters expressed in glial cells as regulators of synapse function. Brain Res Rev 63(1–2):103–112. FDA (Food and Drug Administration). 2004. Critical path update. http://www.fda.gov/ ScienceResearch/SpecialTopics/CriticalPathInitiative/CriticalPathOpportunitiesReports/ ucm077262.htm#execsummary (accessed November 9, 2010). FDA. 2010. Guidance for industry: Qualification process for drug development tools. Rockville, MD: FDA, Center for Drug Evaluation and Research. http://www.fda.gov/ downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM230597. pdf (accessed March 24, 2011). Foran, E., and D. Trotti. 2009. Glutamate transporters and the excitotoxic path to motor neuron degeneration in amyotrophic lateral sclerosis. Antioxid Redox Signal 11(7): 1587–1602. Friedman, H. R., and P. S. Goldman-Rakic. 1994. Coactivation of prefrontal cortex and in- ferior parietal cortex in working memory tasks revealed by 2DG functional mapping in the rhesus monkey. J Neuroscience 14(5 Pt 1):2775–2788. Garrido, M. I., J. M. Kilner, K. E. Stephan, and K. J. Friston. 2009. The mismatch negativity: A review of underlying mechanisms. Clin Neurophysiol 120(3):453–463. Gazerani, P., S. Au, X. Dong, U. Kumar, L. Arendt-Nielsen, and B. E. Cairns. 2010. Botulinum neurotoxin type A (BoNTA) decreases the mechanical sensitivity of nociceptors and in- hibits neurogenic vasodilation in a craniofacial muscle targeted for migraine prophylaxis. Pain 151(3):606–616. Geyer, M. A., K. L. McIlwain, and R. Paylor. 2002. Mouse genetic models for prepulse inhibi- tion: An early review. Mol Psychiatry 7(10):1039–1053. Goldman-Rakic, P. S. 1994. Working memory dysfunction in schizophrenia. J Neuropsychiatry Clin Neuroscience 6(4):348–357. Goodsaid, F., and F. Frueh. 2007. Biomarker qualification pilot process at the U.S. Food and Drug Administration. AAPS J 9(1):E105-E108. Greenwood, T. A., D. L. Braff, G. A. Light, K. S. Cadenhead, M. E. Calkins, D. J. Dobie, R. Freedman, M. F. Green, R. E. Gur, R. C. Gur, J. Mintz, K. H. Nuechterlein, A. Olincy, A. D. Radant, L. J. Seidman, L. J. Siever, J. M. Silverman, W. S. Stone, N. R. Swerdlow, D. W. Tsuang, M. T. Tsuang, B. I. Turetsky, and N. J. Schork. 2007. Initial heritability analyses of endophenotypic measures for schizophrenia: The consortium on the genetics of schizophrenia. Arch Gen Psychiatry 64(11):1242–1250.

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41 APPENDIX A Grewer, C., A. Gameiro, Z. Zhang, Z. Tao, S. Braams, and T. Rauen. 2008. Glutamate for- ward and reverse transport: From molecular mechanism to transporter-mediated release after ischemia. IUBMB Life 60(9):609–619. Hall, M. H., K. Schulze, E. Bramon, R. M. Murray, P. Sham, and F. Rijsdijk. 2006a. Genetic overlap between P300, P50, and duration mismatch negativity. Am J Med Genet B Neu- ropsychiatr Genet 141B(4):336–343. Hall, M. H., K. Schulze, F. Rijsdijk, M. Picchioni, U. Ettinger, E. Bramon, R. Freedman, R. M. Murray, and P. Sham. 2006b. Heritability and reliability of P300, P50 and duration mismatch negativity. Behav Genet 36(6):845–857. IOM (Institute of Medicine). 2008. Neuroscience biomarkers and biosignatures: Converging technologies, emerging partnerships. Washington, DC: The National Academies Press. Jacobson, M. S., J. C. Hung, T. L. Mays, and B. P. Mullan. 2002. The planning and design of a new PET radiochemistry facility. Mol Imaging Biol 4(2):119-127. Jahshan, C., K. S. Cadenhead, A. J. Rissling, K. Kirihara, D. L. Braff, and G. A. Light. In press. Automatic sensory information-processing abnormalities across the illness course of schizophrenia. Psychological Medicine. Javitt, D. C., M. Steinschneider, C. E. Schroeder, and J. C. Arezzo. 1996. Role of cortical N-methyl-D-aspartate receptors in auditory sensory memory and mismatch negativity generation: Implications for schizophrenia. Pro Natl Acad Sci USA 93(21):11962–11967. Javitt, D. C., K. M. Spencer, G. K. Thaker, G. Winterer, and M. Hajós. 2008. Neurophysiologi- cal biomarkers for drug development in schizophrenia. Nat Rev Drug Discov 7(1):68–83. Johannes, C. B., T. K. Le, X. Zhou, J. A. Johnston, and R. H. Dworkin. 2010. The preva- lence of chronic pain in United States adults: Results of an Internet-based survey. J Pain 11(11):1230–1239. Kanai, Y., M. Stelzner, S. Nussberger, S. Khawaja, S. C. Hebert, C. P. Smith, and M. A. Hediger. 1994. The neuronal and epithelial human high affinity glutamate transporter: Insights into structure and mechanism of transport. J Biol Chem 269(32):20599–20606. Kelleher, R. J., III, and M. F. Bear. 2008. The autistic neuron: Troubled translation? Cell 135(3):401–406. Kew, J. N., and J. A. Kemp. 2005. Ionotropic and metabotropic glutamate receptor structure and pharmacology. Psychopharmacology (Berl) 179(1):4–29. Krishnan, G. P., J. L. Vohs, W. P. Hetrick, C. A. Carroll, A. Shekhar, M. A. Bockbrader, and B. F. O’Donnell. 2005. Steady state visual evoked potential abnormalities in schizophre- nia. Clin Neurophysiol 116(3):614–624. Kurylo, D. D., and Y. Gazes. 2008. Effects of ketamine on perceptual grouping in rats. Physiol Behav 95(1–2):152–156. Lakatos, P., G. Karmos, A. D. Mehta, I. Ulbert, and C. E. Schroeder. 2008. Entrainment of neu- ronal oscillations as a mechanism of attentional selection. Science 320(5872):110–113. Lee, M. C., K. K. Ting, S. Adams, B. J. Brew, R. Chung, and G. J. Guillemin. 2010. Char- acterisation of the expression of NMDA receptors in human astrocytes. PLoS One 5(11):e14123. Lesage, A., and T. Steckler. 2010. Metabotropic glutamate mGlu1 receptor stimulation and blockade: Therapeutic opportunities in psychiatric illness. Eur J Pharmacol 639(1–3): 2–16. Lewis, D. A., L. A. Glantz, J. N. Pierri, and R. A. Sweet. 2003. Altered cortical glutamate neurotransmission in schizophrenia: Evidence from morphological studies of pyramidal neurons. Ann N Y Acad Sci 1003:102–112. Light, G. A., L. E. Williams, F. Minow, J. Sprock, A. Rissling, R. Sharp, N. R. Swerdlow, and D. L. Braff. 2010. Electroencephalography (EEG) and event-related potentials (ERPs) with human participants. Curr Protoc Neurosci 6(6):1–24.

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42 GLUTAMATE-RELATED BIOMARKERS IN DRUG DEVELOPMENT Limbrick, D. D., Jr., S. Sombati, and R. J. DeLorenzo. 2003. Calcium influx constitutes the ionic basis for the maintenance of glutamate-induced extended neuronal depolarization associated with hippocampal neuronal death. Cell Calcium 33(2):69–81. Malarkey, E. B., and V. Parpura. 2008. Mechanisms of glutamate release from astrocytes. Neurochem Int 52(1–2):142–154. Narrow, W. E., D. S. Rae, L. N. Robins, and D. A. Regier. 2002. Revised prevalence estimates of mental disorders in the United States: Using a clinical significance criterion to reconcile 2 surveys’ estimates. Arch Gen Psychiatry 59(2):115–123. Niswender, C. M., and P. J. Conn. 2010. Metabotropic glutamate receptors: Physiology, phar- macology, and disease. Ann Rev Pharmacol Toxicol 50:295–322. Olive, M. F. 2009. Metabotropic glutamate receptor ligands as potential therapeutics for ad- diction. Curr Drug Abuse Rev 2(1):83–98. Pacher, P., S. Batkai, and G. Funos. 2006. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev 58(3):389–462. Paulus, M. P., J. S. Feinstein, G. Castillo, A. N. Simmons, and M. B. Stein. 2005. Dose- dependent decrease of activation in bilateral amygdala and insula by lorazepam during emotion processing. Arch Gen Psychiatry 62:282–288. Pike, V. W. 2009. PET radiotracers: Crossing the blood–brain barrier and surviving metabo- lism. Trends in Pharmacological Sciences 30(8):431–440. Pleasure, D. 2008. Diagnostic and pathogenic significance of glutamate receptor autoantibod- ies. Arch Neurol 65(5):589–592. Rothman, D. L., K. L. Behar, F. Hyder, and R. G. Shulman. 2003. In vivo NMR studies of the glutamate neurotransmitter flux and neuroenergetics: Implications for brain function. Annu Rev Physiol 65:401–427. Rothstein, J. D., L. J. Martin, and R. W. Kuncl. 1992. Decreased glutamate transport by the brain and spinal cord in amyotrophic lateral sclerosis. N Engl J Med 326(22):1464–1468. Salvadore, G., B. R. Cornwell, F. Sambataro, D. Latov, V. Colon-Rosario, F. Carver, T. Holyroyd, N. DiazGranados, R. Machado-Vieira, C. Grillon, W. C. Drevets, and C. A. Zarate, Jr. 2010. Anterior cingulate desynchronization and functional connectivity with the amygdale during a working memory task predict rapid antidepressant response to ketamine. Neuropsychopharmacology 35(7):1415–1422. Sanacora, G., C. A. Zarate, J. H. Krystal, and H. K. Manji. 2008. Targeting the glutamater- gic system to develop novel, improved therapeutics for mood disorders. Nat Rev Drug Discov 7(5):426–437. Swanson, C. J., M. Bures, M. P. Johnson, A. M. Linden, J. A. Monn, and D. D. Schoepp. 2005. Metabotropic glutamate receptors as novel targets for anxiety and stress disorders. Nat Rev Drug Discov 4(2):131–144. Tanaka, K. 2000. Functions of glutamate transporters in the brain. Neuroscience Res. 37(1):15–19. Terry, G. E., J. Hirvonen, J. S. Liow, S. S. Zoghbi, R. Gladding, J. T. Tauscher, J. M. Schaus, L. Phebus, C. C. Felder, C. L. Morse, S. R. Donohue, V. W. Pike, C. Halldin, and R. B. Innis. 2010. Imaging and quantitation of cannabinoid CB1 receptors in human and monkey brains using (18)F-labeled inverse agonist radioligands. J Nucl Med (1):112–120. Tononi, G., and C. Cirelli. 2006. Sleep function and synaptic homeostasis. Sleep Med Rev 10(1):49–62. Umbricht, D., and S. Krljes. 2005. Mismatch negativity in schizophrenia: A meta-analysis. Schizophr Res 76(1):1–23. Umbricht, D., L. Schmid, R. Koller, F. X. Vollenweider, D. Hell, and D. C. Javitt. 2000. Ketamine-induced deficits in auditory and visual context-dependent processing in healthy volunteers: Implications for models of cognitive deficits in schizophrenia. Archives Gen Psychiatry 57(12):1139–1147.

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43 APPENDIX A Verrall, L., P. W. Burnet, J. F. Betts, and P. J. Harrison. 2010. The neurobiology of D-amino acid oxidase and its involvement in schizophrenia. Mol Psychiatry 15(2):122–137. Wang, X. P., and H. L. Ding. 2008. Alzheimer’s disease: Epidemiology, genetics, and beyond. Neurosci Bull 24(2):105–109. Watson, T. D., I. L. Petrakis, J. Edgecombe, A. Perrino, J. H. Krystal, and D. H. Mathalon. 2009. Modulation of the cortical processing of novel and target stimuli by drugs affecting glutamate and GABA neurotransmission. Int J Neuropsychopharmacol 12(3):357–370. WHO (World Health Organization). 2001. The World Health Report 2001—Mental Health: New Understanding, New Hope. Geneva, World Health Organization. http://www.who. int/whr/ (accessed March 24, 2011). Writer, B. W., and J. E. Schillerstrom. 2009. Psychopharmacological treatment for cognitive impairment in survivors of traumatic brain injury: A critical review. J Neuropsychiatry Clin Neurosci 21(4):362–370. Xiong, Z. G., G. Pignataro, M. Li, S. Y. Chang, and R. P. Simon. 2008. Acid-sensing ion channels (ASICs) as pharmacological targets for neurodegenerative diseases. Curr Opin Pharmacol 8(1):25–32. Yüksel, C., and D. Öngür. 2010. Magnetic resonance spectroscopy studies of glutamate-related abnormalities in mood disorders. Biol Psychiatry 68:785–794. Zarate, C. A., Jr., J. B. Singh, P. J. Carlson, N. E. Brutsche, R. Ameli, D. A. Luckenbaugh, D. S. Charney, and H. K. Manji. 2006. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry 63(8):856–864. Zarate, C., Jr., R. Machado-Vieira, I. Henter, L. Ibrahim, N. Diazgranados, and G. Salvadore. 2010. Glutamatergic modulators: The future of treating mood disorders? Harv Rev Psychiatry 18(5):293–303.

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