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Neurobiology and Functional Progression in Schizophrenia

Published online by Cambridge University Press:  07 November 2014

L. Fredrik Jarskog
L. Fredrik Jarskog*
Affiliation:
Dr. Jarskog is associate professor in the Department of Psychiatry at the, University of North Carolina School of Medicine in Chapel Hill
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Abstract

Schizophrenia is a neurodevelopmental disorder associated with persistent symptomatology, severe functional disability, and residual morbidity characteristic of neurodegenerative brain diseases. The illness begins with genetic susceptibility and generally expresses itself after puberty through subtle changes that begin during the prodromal stage. Symptoms get progressively worse and tend to become more resistant to treatment with each relapse. Evidence for a neuroprotective effect of some forms of early treatment is beginning to emerge. While the underlying mechanisms remain uncertain, atypical antipsychotics may counteract some of the progressive deteriorative effects by enhancing synaptic plasticity and cellular resilience. However, identifying and treating patients in the earliest disease states presents methodological challenges as there is no consensus on the best methods of intervention and differences in at-risk children are not readily detectable or substantial enough to predict which ones will develop schizophrenia.

In this expert roundtable supplement, Jeffrey A. Lieberman, MD, reviews the historical context of progressive deterioration in schizophrenia. Next, Diana O. Perkins, MD, MPH, reviews some of the challenges to early identification of illness as well as the impact of early versus delayed treatment. Finally, L. Fredrik Jarskog, MD, focuses on the neurobiology of functional progression in schizophrenia as well as pharmacology and the potential for neuroprotection.

Type
Research Article
Information
CNS Spectrums , Volume 12 , Issue S4 , 2007 , pp. 9 - 12
Copyright
Copyright © Cambridge University Press 2007

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References

1.Pantelis, C, Velakoulis, D, McGorry, PD, et al.Neuroanatomical abnormalities before and after onset of psychosis: a cross-sectional and longitudinal MRI comparison. Lancet. 2003;361:281–288.CrossRefGoogle ScholarPubMed
2.Thompson, PM, Vidal, C, Giedd, JN, et al.Mapping adolescent brain change reveals dynamic wave of accelerated gray matter loss in very early-onset schizophrenia. Proc Natl Acad Sci U S A. 2001;98(20):11650–11655.CrossRefGoogle ScholarPubMed
3.Cahn, W, Pol, HE, Lems, EB, et al.Brain volume changes in first-episode schizophrenia: a 1-year follow-up study. Arch Gen Psychiatry. 2002;59:1002–1010.CrossRefGoogle ScholarPubMed
4.Thompson, PM, Hayashi, KM, de Zubicaray, G, et al.Dynamics of gray matter loss in Alzheimer's disease. J Neurosci. 2003;23(3):994–1005.CrossRefGoogle ScholarPubMed
5.Jarskog, LF, Gilmore, JH. Neuroprogressive theories. In: Lieberman, JA, Stroup, TS, Perkins, DO, eds. Textbook of Schizophrenia. Washington, DC: American Psychiatric Publishing, Inc.; 2006:137–149.Google Scholar
6.Selemon, LD, Rajkowska, G, Goldman-Rakic, PS. Elevated neuronal density in prefrontal area 46 in brains from schizophrenic patients: application of a three-dimensional, stereologic counting method. J Comp Neurol. 1998;392:402–412.3.0.CO;2-5>CrossRefGoogle ScholarPubMed
7.Stark, AK, Uylings, HB, Sanz-Arigita, E, et al.Glial cell loss in the anterior cingulate cortex, a subregion of the prefrontal cortex, in subjects with schizophrenia. Am J Psychiatry. 2004;161(5):882–888.CrossRefGoogle ScholarPubMed
8.Black, JE, Kodish, IM, Grossman, AW, et al.Pathology of layer V pyramidal neurons in the prefrontal cortex of patients with schizophrenia. Am J Psychiatry. 2004;161(4):742–744.CrossRefGoogle Scholar
9.Glantz, LA, Lewis, DA. Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia. Arch Gen Psychiatry. 2000;57:65–73.CrossRefGoogle ScholarPubMed
10.Harrison, PJ, Weinberger, DR. Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence. Mol Psychiatry. 2005;10:40–68.CrossRefGoogle ScholarPubMed
11.Goff, DC, Coyle, JT. The emerging role of glutamate in the pathophysiology and treatment of schizophrenia. Am J Psychiatry. 2001;158(9):1367–1377.CrossRefGoogle ScholarPubMed
12.Konradi, C, Heckers, S. Molecular aspects of glutamate dysregulation: implications for schizophrenia and its treatment. Pharmacol Ther. 2003;97:153–179.CrossRefGoogle ScholarPubMed
13.Lieberman, JA, Tollefson, GD, Charles, C, et al.Antipsychotic drug effects on brain morphology in first-episode psychosis. Arch Gen Psychiatry. 2005;62(4):361–370.CrossRefGoogle ScholarPubMed
14.Lidow, MS, Song, ZM, Castner, SA, Allen, PB, Greengard, P, Goldman-Rakic, PS. Antipsychotic treatment induces alterations in dendrite- and spine-associated proteins in dopamine-rich areas of the primate cerebral cortex. Biol Psychiatry. 2001;49(1):1–12.CrossRefGoogle ScholarPubMed
15.Critchlow, HM, Maycox, PR, Skepper, JN, Krylova, O. Clozapine and haloperidol differentially regulate dendritic spine formation and synaptogenesis in rat hippocampal neurons. Mol Cell Neurosci. 2006;32(4):356–365.CrossRefGoogle ScholarPubMed