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Research and treatment strategies in first-episode psychoses: The Pittsburgh experience

Published online by Cambridge University Press:  06 August 2018

M. S. Keshavan ,
N. R. Schooler ,
J. A. Sweeney ,
G. L. Haas  and
J. W. Pettegrew
M. S. Keshavan*
Affiliation:
Department of Psychiatry, Western Psychiatric Institute and Clinic, Pittsburgh, Pennsylvania, USA
N. R. Schooler
Affiliation:
Departments of Psychiatry and Neurology, University of Pittsburgh, Pennsylvania, USA
J. A. Sweeney
Affiliation:
Departments of Psychiatry and Neurology, University of Pittsburgh, Pennsylvania, USA
G. L. Haas
Affiliation:
Departments of Psychiatry and Neurology, University of Pittsburgh, Pennsylvania, USA
J. W. Pettegrew
Affiliation:
University of Pittsburgh, Graduate School of Public Health, Pittsburgh, Pennsylvania, USA
*
Correspondence: M. S. Keshavan, Department of Psychiatry, Western Psychiatric Institute and Clinic, 3811 O'Hara Street, Pittsburgh, PA 15213, USA. Fax: (412) 624 4699; e-mail: keshavan+@pitt.edu
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Abstract

Background Studies of first-episode patients allow investigation of the biological basis of psychotic disorders without the potential confounds of prior treatment and illness chronicity. Prospective studies of this population can clarify the impact of illness course and treatment on neurobiology.

Method We summarise preliminary findings from our ongoing magnetic resonance imaging and spectroscopy studies of first-episode schizophrenia patients being conducted prospectively from index evaluations through a period of two years; during this period, patients were treated with either a conventional antipsychotic such as haloperidol, or the atypical risperidone.

Results Baseline neurobiological evaluations in first-episode schizophrenia patients have revealed evidence for structural and functional brain abnormalities consistent with a neurodevelopmental model of this illness. Our preliminary data support the value of risperidone as an antipsychotic drug of first choice among patients with early schizophrenic illness.

Conclusions Focused studies of first-episode patients have the potential to unravel pathophysiology of schizophrenic illness. Such knowledge is critical for more effective early detection, intervention and even prevention of this enigmatic disorder.

Information

Type
Research Article
Information
The British Journal of Psychiatry , Volume 172 , Issue S33: Verging on reality , June 1998 , pp. 60 - 65
Copyright
Copyright © 1998 The Royal College of Psychiatrists 

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References

Aguilar, E. J., Bagwell, W.W., Haas, G., et al (1995) Cerebral asymmetry, gender, and early schizophrenia. Schizophrenia Research, 15, 75.Google Scholar
American Psychiatric Association (1987) Diagnostic and Statistical Manual of Mental Disorders (3rd edn) (DSM–III–R). Washington, DC: APA.Google Scholar
Andreasen, N. C. (1982) Negative symptoms in schizophrenia. Archives of General Psychiatry, 39, 784–788.Google Scholar
Andreasen, N. C. (1984) The Scale for the Assessment of Positive Symptoms (SAPS). Iowa City, IA: University of Iowa.Google Scholar
Bagwell, W.W., Aguilar, E. J., Haas, G., et al (1995) Morphology of the corpus callosum in first-break schizophrenic patients: an MRI study. Schizophrenia Research, 15, 87 Google Scholar
Cannon, T. D., Mednick, S. A., Parnas, J., et al (1993) Developmental brain abnormalities in the offspring of schizophrenic mother. I. Contributions of genetic and perinatal factors. Archives of General Psychiatry, 50, 551–564.Google Scholar
Chakos, M. H., Lieberman, J. A., Bilder, R. M., et al (1994) Increase in caudate nuclei volumes of first-episode schizophrenic patients taking antipsychotic drugs. American Journal of Psychiatry, 151, 1430–1436.Google ScholarPubMed
Chakos, M. H., Lieberman, J. A., Alvir, J., et al (1995) Caudate nuclei volumes in schizophrenic patients treated with typical antipsychotics or clozapine. Lancet, 345, 456–457.Google Scholar
Chugani, H.T., Phelps, M. E. & Mazziotta, J. C. (1987) Positron emission tomography study of human brain functional development. Annals of Neurology, 22, 487–497.Google Scholar
DeLisi, L. E. (1995) A prospective follow-up study of brain morphology and cognition in first-episode schizophrenic patients: preliminary findings. Biological Psychiatry, 38, 349–360.Google Scholar
Doraiswamy, P. M., Tupler, L. A. & Krishnan, K. R. (1995) Neuroleptic treatment and caudate plasticity. Lancet, 345, 734–735.Google ScholarPubMed
Endicott, J., Spitzer, R. L., Fleiss, J., et al (1976) The Global Assessment Scale: A procedure for measuring overall severity of psychiatric disturbance. Archives of General Psychiatry, 33, 766–771.Google Scholar
Falloon, I. R. H., Kydd, R. R., Coverdale, J. H., et al (1996) Early detection and intervention of initial episodes of schizophrenia. Schizophrenia Bulletin, 22, 271–282.Google Scholar
Feinberg, I. (1974) Changes in sleep cycle patterns with age. Journal of Psychiatry Research, 10, 283–306.Google Scholar
Feinberg, I. (1983) Schizophrenia: caused by a fault in programmed synaptic elimination during adolescence? Journal of Psychiatry Research, 17, 319.CrossRefGoogle Scholar
Feinberg, I., Thode, H. C., Chugani, H. T., et al (1990) Gamma distribution model describes maturational curves for delta wave amplitude, cortical metabolic rate and synaptic density. Journal of Theoretical Biology, 142, 149–161.Google Scholar
Fish, B. (1977) Infant predictors of the longitudinal course of schizophrenic development. Schizophrenia Bulletin, 13, 395–409.CrossRefGoogle Scholar
Goodman, R. (1989) Neuronal mis-connections and psychiatric disorder. Is there a link? British Journal of Psychiatry, 154, 292–299.Google Scholar
Harvey, I., Ron, M. A., Du Boulay, G., et al (1993) Reduction in cortical volume in schizophrenia on magnetic resonance imaging. Psychological Medicine, 23, 591–604.Google Scholar
Huttenlocher, P. R. (1979) Synaptic density in human frontal cortex. Developmental changes and effects of aging. Brain Research, 163, 195.Google Scholar
Janowsky, J. S. & Finlay, B. L. (1986) The outcome of brain damage: the fate of normal neuronal loss and retraction. Developmental Medicine and Child Neurology, 28, 375–389.CrossRefGoogle Scholar
Jaskiw, G. E., Juliano, D. M., Goldberg, T. E., et al (1994) Cerebral ventricular enlargement in schizophreniform disorder does not progress. A seven year follow-up study. Schizophrenia Research, 14, 23–28.Google Scholar
Kato, T., Shioiri, T., Murashita, J., et al (1995) Lateralized abnormality of high-energy phosphate and bilateral reduction of phosphomonoester measured by phosphorus-31 magnetic resonance spectroscopy of the frontal lobes in schizophrenia. Psychiatry Research, 61, 151–160.Google Scholar
Keshavan, M. S., Kapur, S. & Pettegrew, J. W. (1991) Magnetic resonance spectroscopy: Potential, pitfalls and promise. American Journal of Psychiatry, 148, 976–985.Google Scholar
Keshavan, M. S. & Schooler, N. R. (1992) First-episode studies in schizophrenia: criteria and characterization. Schizophrenia Bulletin, 18, 491.Google Scholar
Keshavan, M. S., Pettegrew, J. W., Bagwell, W.W., et al (1994a) Gray matter volume deficits in first-episode schizophrenia. Biological Psychiatry, 35, 713.Google Scholar
Keshavan, M. S., Anderson, S. & Pettegrew, J. W. (1994b) Is schizophrenia due to excessive synaptic pruning in the prefrontal cortex? Journal of Psychiatric Research, 28, 239.Google Scholar
Keshavan, M. S., Bagwell, W.W., Haas, G. L., et al (1994c) Changes in caudate volume with neuroleptic treatment. Lancet, 344, 1434.Google Scholar
Keshavan, M. S., Bagwell, W.W., Reynolds, C. E., et al (1995) Slow wave sleep deficits in schizophrenia: pathophysiological significance. Psychiatry Research, 571, 91–100.Google Scholar
Keshavan, M. S., Kisler, T., Rosenberg, D., et al (1996) Decreased caudate volume in first-episode schizophrenia. Biological Psychiatry, 39, 500–501.Google Scholar
Kopala, L. C., Fredrikson, D., Good, K. P., et al (1996) Symptoms in neuroleptic-naive, first-episode schizophrenia: response to risperidone. Biological Psychiatry, 39, 296–299.CrossRefGoogle ScholarPubMed
Marsh, L., Suddath, R. L., Higgins, N., et al (1994) Medial temporal lobe structures in schizophrenia: relationship of size to duration of illness. Schizophrenia Research, 11, 225–238.CrossRefGoogle ScholarPubMed
Marder, S. R. & Meibach, R. C. (1994) Risperidone in the treatment of chronic schizophrenia. American Journal of Psychiatry, 151, 825–835.Google Scholar
McEvoy, J. P., Hogarty, G. E. & Steingard, S. (1991) Optimal close of neuroleptic in acute schizophrenia: a controlled study of neuroleptic threshold and higher haloperidol dose. Archives of General Psychiatry, 481, 739.Google Scholar
McGlashan, T. H. & Johannessen, J. O. (1996) Early detection and intervention with schizophrenia: rationale. Schizophrenia Bulletin, 22, 201–217.Google Scholar
McGorry, P. D., Edwards, J., Mihalopoulos, C., et al (1996) EPPIC: an evolving system of early detection and optimal management. Schizophrenia Bulletin, 22, 305–322.Google Scholar
Meshul, C. K. & Casey, D. E. (1989) Regional, reversible intrastructural changes in rat brain with chronic neuroleptic treatment. Brain Research, 489, 338–546.Google Scholar
Minshew, N. J., Panchalingam, K., Dombrowski, S. M., et al (1992) Developmentally regulated changes in brain membrane metabolism. Biological Psychiatry, 31, 62.Google Scholar
Mukherjee, S. & Mahadik, S. P. (1994) A new paradigm for schizophrenia? Schizophrenia Research, 13, 191–194.CrossRefGoogle ScholarPubMed
Murray, R. M. & Lewis, S. W. (1987) Is schizophrenia a neurodevelopmental disorder? British Medical Journal, 295, 681.Google Scholar
Overall, J. E. & Gorham, D. R. (1962) The Brief Psychiatric Rating Scale. Psychological Reports, 10, 799–812.Google Scholar
Pettegrew, J.W., Keshavan, M. S., Panchalingam, K., et al (1991) Alterations in brain high-energy phosphate and phospholipid metabolism in first episode, drug-naive schizophrenia. A pilot study of the dorsal prefrontal cortex by in vivo 31P NMR spectroscopy. Archives of General Psychiatry, 48, 563.Google ScholarPubMed
Pieri, J., Gupta, B. K., Bagwell, W. W., et al (1995) MRI abnormalities in first-episode schizophrenia: association with neurological impairment. Schizophrenia Research, 15, 87.Google Scholar
Sanders, R. D., Keshavan, M. S. & Schooler, N. R. (1994) Neurological examination abnormalities in neuroleptic-naive patients with first-break schizophrenia: preliminary results. American Journal of Psychiatry, 151, 1231–1233.Google Scholar
Selemon, L. D., Rajkowska, G. & Goldman-Rakic, P. S. (1995) Abnormally high neuronal density in the schizophrenic cortex. Archives of General Psychiatry, 52, 805–818.Google Scholar
Stanley, J. F., Drost, D. J., Williamson, P. C., et al (1995) In vivo proton MRS study of glutamate and schizophrenia. In NMR Spectroscopy in Psychiatric Brain Disorders (eds Nasrallah, H. A. & Pettegrew, J.W.). Washington, DC: APA.Google Scholar
Stevens, J. R. (1992) Abnormal reinnervation as a basis for schizophrenia: a hypothesis. Archives of General Psychiatry, 49, 238–243.Google Scholar
Sweeney, J. A., Haas, G. L. & Li, S. (1992) Neuropsychological and eye movement abnormalities in first-episode and chronic schizophrenia. Schizophrenia Bulletin, 18, 283–293.Google Scholar
Sweeney, J. A., Luna, B., Srinivasagam, N. M., et al (1998) Eye tracking dysfunction in schizophrenia: Evidence for dysfunction in the frontal eye fields. Biological Psychiatry in press.Google Scholar
Turetsky, B., Cowell, P. E., Gur, R. C., et al (1995) Frontal and temporal lobe brain volumes in schizophrenia. Relationship to symptoms and clinical subtype. Archives of General Psychiatry, 52, 1061–1070.Google Scholar
Van Ooyen, A., Van Pelt, J. & Corner, M. A. (1995) Implications of activity dependent neurite outgrowth for neuronal morphology and network development. Journal of Theoretical Biology, 172, 63–82.CrossRefGoogle ScholarPubMed
Walker, E. F. & Lewine, R. J. (1990) Predictions of adult-onset schizophrenia from childhood home movies of the parents. American Journal of Psychiatry, 147, 1052–1056.Google Scholar
Weinberger, D. R. (1987) Implications of normal brain development for the pathogenesis of schizophrenia. Archives of General Psychiatry, 44, 660–667.Google Scholar
Weinberger, D. R. (1988) Premorbid neuropathology in schizophrenia. Lancet, ii, 445.Google Scholar
Weinberger, D. R. (1995) From neuropathology to neurodevelopment. Lancet, 346, 552–557.Google Scholar
Wible, C. G., Shenton, M. E., Hokama, H., et al (1995) Prefrontal cortex and schizophrenia. A quantitative magnetic resonance imaging study. Archives of General Psychiatry, 52, 279–288.Google Scholar
Wyatt, R. J. (1991) Neuroleptics and the natural course of schizophrenia. Schizophrenia Bulletin, 17, 325–351.Google Scholar
Zarcone, V. P. & Benson, K. L. (1994) Sleep and schizophrenia. In Principles and Practice of Sleep Medicine (eds Kreiger, M. H., Roth, T. & Dement, W.C.). New York: W. B. Saunders.Google Scholar
Zipursky, R. B., Lim, K. O., Sullivan, E. V., et al (1992) Widespread grey matter volume deficits in schizophrenia. Archives of General Psychiatry, 49, 195–205.Google Scholar

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