eBriefing

Biomarkers for Schizophrenia

Biomarkers for Schizophrenia
Reported by
Angelo DePalma

Posted October 15, 2009

Overview

A biomarker is a biological characteristic that indicates the presence of a specific condition. Neuroscientists working on schizophrenia are seeking biomarkers that could be used to develop early diagnostics and drug treatments for the disease. These could be biologically active molecules (proteins, genes, metabolites) or information extracted from imaging tools that indicate the presence of the disease. Biomarkers may also provide information on a treatment's mechanism of action.

A January 24, 2006, meeting of the Academy's Biochemical Pharmacology Discussion Group focused on several efforts to identify biomarkers for schizophrenia. Kevin Spencer discussed the GABAergic model of schizophrenia, which is rooted in chandelier cell abnormalities, as an interesting area of investigation into new schizophrenia drugs. Georg Winterer looked at the connection between dopamine levels and the disruption of the signal-to-noise ratio in the prefrontal cortex of individuals with schizophrenia. Gunvant Thaker spoke of endophenotypes—traits that are not direct symptoms of the condition but that are nevertheless associated with it—which may themselves serve as treatment targets and diagnostics. Daniel Javitt focused on "very significant deficits" in basic sensory processing, particularly the auditory and visual systems.

Use the tabs above to find a meeting report and multimedia from this event.

Web Sites

Schizophrenia.com
One-stop Web site for patients and families affected by schizophrenia, covering the biology, psychiatry, and treatment of most forms of schizophrenia.

Medline Plus: Schizophrenia
Gateway to government and health organization Web sites on schizophrenia, including resources from the National Institutes of Health, National Institute of Mental Health, and American Psychiatric Association. Interesting links to research and clinical trial information.


Books

Green, M. F. 2001. Schizophrenia Revealed: From Neurons to Social Interactions. Norton, New York.

Hirsch, S. R. & D. Weinberger, Eds. 2003. Schizophrenia. Blackwell Science, Oxford, UK.

McGuffin, P., M. J. Owen & I. I. Gottesman, Eds. 2002. Psychiatric Genetics and Genomics. Oxford University Press, New York.

Torrey, E. F. 2001. Surviving Schizophrenia: A Manual for Families, Consumers, and Providers. 4th ed. HarperCollins, New York.


Articles

Neurophysiological Correlates of Disordered Perception and Cognition in Schizophrenia

Rosen, V. M., T. Sunderland, J. Levy, et al. 2005. Apolipoprotein E and category fluency: evidence for reduced semantic access in healthy normal controls at risk for developing Alzheimer's disease. Neuropsychologia 43: 647-658.

Spencer, K. M. & R. W. McCarley. 2005. Visual hallucinations, attention, and neural circuitry: perspectives from schizophrenia research. Behav. Brain Sci. 28: 774.

Spencer, K. M., P. G. Nestor, M. A. Niznikiewicz, et al. 2003. Abnormal neural synchrony in schizophrenia. J. Neurosci. 23: 7407-7411. Full Text

Spencer, K. M., P. G. Nestor, R. Perlmutter, et al. 2004. Neural synchrony indexes disordered perception and cognition in schizophrenia. Proc. Natl. Acad. Sci. USA 101: 17288-17293. Full Text

Symond, M. P., A. W. Harris, E. Gordon & L. M. Williams. 2005. "γ synchrony" in first-episode schizophrenia: a disorder of temporal connectivity? Am. J. Psychiatry 162: 459-465. Full Text

Yeragani, V. K., D. Cashmere, J. Miewald, et al. 2006. Decreased coherence in higher frequency ranges (β and γ) between central and frontal EEG in patients with schizophrenia: a preliminary report. Psychiatry Res. 141: 53-60.

Impaired Neuronal Processing of Frontal Cortical Regions in Schizophrenic Patients

Gallinat, J., G. Winterer, C. S. Herrmann & D. Senkowski. 2004. Reduced oscillatory γ-band responses in unmedicated schizophrenic patients indicate impaired frontal network processing. Clin. Neurophysiol. 115: 1863-1874.

Lehmann, D., P. L. Fabe, S. Galderisi, et al. 2005. EEG microstate duration and syntax in acute, medication-naive, first-episode schizophrenia: a multi-center study. Psychiatry Res. 138: 141-156.

Winterer, G., R. Coppola, M. F. Egan, et al. 2003. Functional and effective frontotemporal connectivity and genetic risk for schizophrenia. Biol. Psychiatry 54:1181-1192.

Winterer, G., R. Coppola, T. E. Goldberg, et al. 2004. Prefrontal broadband noise, working memory, and genetic risk for schizophrenia. Am. J. Psychiatry 161: 490-500. Full Text

Winterer, G. & D. R. Weinberger. 2004. Genes, dopamine and cortical signal-to-noise ratio in schizophrenia. Trends Neurosci. 27: 683-690.

Schizophrenia Endophenotypes as Treatment Targets

Avila, M. T., L. E. Hong, A. Moates, et al. 2006. Role of anticipation in schizophrenia-related pursuit initiation deficits. J. Neurophysiol. 95: 593-601.

Hong, L. E., M. T. Avila, I. Wonodi et al. 2005. Reliability of a portable head-mounted eye tracking instrument for schizophrenia research. Behav. Res. Methods 37: 133-138.

Srivastava, V., P. G. Varma, S. Prasad, et al. 2006. Genetic susceptibility to tardive dyskinesia among schizophrenia subjects: IV. Role of dopaminergic pathway gene polymorphisms. Pharmacogenet. Genomics 16: 111-117.

Tunbridge, E. M., P. J. Harrison & D. R. Weinberger. 2006. Catechol-o-methyltransferase, cognition, and psychosis: val158 met and beyond. Biol. Psychiatry. E-pub ahead of print.

Wonodi, I., L. E. Hong, M. T. Avila, et al. 2005. Association between polymorphism of the SNAP29 gene promoter region and schizophrenia. Schizophr. Res. 78: 339-341.

Wonodi, I., L. E. Hong & G. K. Thaker. 2005. Psychopathological and cognitive correlates of tardive dyskinesia in patients treated with neuroleptics. Adv. Neurol. 96: 336-349.

Mismatch Negativity and Beyond: Sensory Deficits As Endophenotypes and Cognitive Predictors in Schizophrenia

Ardekani, B. A., A. Bappal, D. D'Angelo, et al. 2005. Brain morphometry using diffusion-weighted magnetic resonance imaging: application to schizophrenia. Neuroreport 16: 1455-1459.

Kim, D., G. Wylie, R. Pasternak, et al. 2006. Magnocellular contributions to impaired motion processing in schizophrenia. Schizophr. Res. 82: 1-8.

Neeman, G, M. Blanaru, B. Bloch, et al. 2005. Relation of plasma glycine, serine, and homocysteine levels to schizophrenia symptoms and medication type. Am. J. Psychiatry 162: 1738-1740.

Penschuck, S., P. Flagstad, M. Didriksen, et al. 2006. Decrease in parvalbumin-expressing neurons in the hippocampus and increased phencyclidine-induced locomotor activity in the rat methylazoxymethanol (MAM) model of schizophrenia. Eur. J. Neurosci. 23: 279-284.

Revheim, N., I. Schechter, D. Kim, et al. 2006. Neurocognitive and symptom correlates of daily problem-solving skills in schizophrenia. Schizophr. Res. E-pub ahead of print.

Rujescu, D, A. Bender, M. Keck, et al. 2006. A pharmacological model for psychosis based on n-methyl-d-aspartate receptor hypofunction: molecular, cellular, functional and behavioral abnormalities. Biol. Psychiatry. E-pub ahead of print.

Speakers

Kevin M. Spencer, PhD

VA Boston Healthcare System
Harvard Medical School
e-mail | web site | publications

Kevin Spencer is a research health scientist at VA Boston Healthcare System and an assistant professor at the Harvard Medical School Department of Psychology. His interests lie in understanding how cognitive processes arise from the dynamics of neural systems, both in healthy individuals and in clinical populations. He focuses on three areas: neural synchrony in healthy individuals and in schizophrenic patients, ERP indices of executive control (and the way they are affected in schizophrenia), and prefrontal cortex function in schizophrenia.

Spencer completed his graduate training at the University of Illinois at Urbana-Champaign. He has received several awards for his work, including the National Alliance for Research on Schizophrenia and Depression Young Investigator Award and the Scottish Rite Fellowship in Schizophrenia.

Georg Winterer, MD

Heinrich Heine University Düsseldorf
e-mail | publications

Georg Winterer is associate professor of psychiatry, chief of laboratory for molecular neuroimaging and electrophysiology, and clinical director of general psychiatry at Heinrich Heine University Düsseldorf.

Winterer received his medical degree from the Medical School of the Free University of Berlin and obtained board certification in psychiatry and psychotherapy. He then went on to complete his doctoral dissertation in neuroscience. Before coming back to Germany to join the faculty of Heinrich-Heine University Düsseldorf, Winterer worked as a clinical psychiatrist at the National Institutes of Health. While at NIH, Winterer also performed research at the clinical brain disorders branch as well as at the laboratory of neurogenetics.

Gunvant K. Thaker, MD

Maryland Psychiatric Research Center
e-mail | web site | publications

Gunvant Thaker is a research psychiatrist with a broad research interest in understanding the etiology of schizophrenia leading to early preventive and intervention strategies in psychosis. His recent work has focused on examining clinical and biological vulnerability markers of schizophrenia. Data are being collected for formal genetic linkage analysis of the pursuit abnormality in relatives of patients with schizophrenia. Other studies use pharmacological probes in order to identify preventive strategies for psychosis in at risk subjects and to reverse the subtle cognitive deficits observed in such high risk subjects.

Thaker obtained his medical degree from Baroda University in India and completed his residency in psychiatry at the Medical College of Ohio and at the Lafayette Clinic. In addition to being professor at the Maryland Psychiatric Research Center, he serves as adjunct professor at the University of Texas South Western Medical Center and is the chief of the schizophrenia related disorder program at the Maryland Psychiatric Research Center. Thaker has been appointed associate editor of Schizophrenia Bulletin and serves as reviewer for several psychiatric journals, such as American Journal of Psychiatry and Journal of Psychiatric Research.

Daniel C. Javitt, MD, PhD

Nathan Kline Institute for Psychiatric Research
e-mail | web site | publications

Daniel Javitt is professor of psychiatry and neuroscience at the New York University School of Medicine. He also serves as director for the program in cognitive neuroscience and schizophrenia at the Nathan Kline Institute for Psychiatric Research in Orangeburg, New York. Javitt's research interests include cognitive and neurophysiological abnormalities in schizophrenia and mechanisms of phencyclidine (PCP) induced psychosis.

Javitt received both his MD and PhD degrees from Albert Einstein College of Medicine in Bronx, New York and completed residency training in psychiatry at Montefiore Medical Center. Javitt is a recipient of research awards from the American Psychiatric Association, the Society for Biological Psychiatry, the American College of Neuropsychopharmacology, and the State of New York. He has written numerous articles, chapters, reviews, and pamphlets. This literature has been featured in Scientific American, American Journal of Psychiatry, Archives of General Psychiatry, Molecular Pharmacology, Saddock and Kaplan's Comprehensive Textbook of Psychiatry, and the television special, "Prisoners of the Brain."


Angelo DePalma

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Angelo DePalma is a freelance writer based in Newton, New Jersey. In 1984, he received a PhD in chemistry from the State University of New York, Stony Brook. His work appears in a dozen pharmaceutical industry trade magazines, and he is the author of a bestselling book on vitamins and supplements.