Hostname: page-component-78c5997874-s2hrs Total loading time: 0 Render date: 2024-11-15T12:11:17.014Z Has data issue: false hasContentIssue false
  • English
  • Français

Neuroprotection: A New Strategy in the Treatment of Schizophrenia

Published online by Cambridge University Press:  07 November 2014

Jeffrey A. Lieberman ,
Peter F. Buckley  and
Diana O. Perkins
Jeffrey A. Lieberman
Affiliation:
Dr. Lieberman is chairman of the Department of Psychiatry at, Columbia University College of Physiciansand Surgeons, director of the New York State Psychiatric Institute and the Lieber Center for Schizophrenia Research, and psychiatrist-in-chief of the New York-Presbyterian Hospital and Columbia University Medical Center in New York City.
Peter F. Buckley
Affiliation:
Dr. Buckley is professor and chairman in the Department of Psychiatry and Health Behavior at the, Medical College of Georgia, in Augusta.
Diana O. Perkins
Affiliation:
Dr. Perkins is professor of psychiatry, medical director of Outreach and Support Intervention Services, and director of the Schizophrenia Treatment and Evaluation Program at the, University of North Carolinaat Chapel Hill.
Get access Rights & Permissions [Opens in a new window]

Abstract

Intervention in the progression of schizophrenia is an effort not just to deter psychosis but also to protect the brain from physiologic deterioration. Neurodegeneration is believed to result from neurochemical dysregulation during the onset of schizophrenia. Deterioration accrued over recurring psychotic episodes causes cumulative loss of cell processes, loss of gray matter volume, and apoptosis. Neurodegeneration ultimately results in persistent symptomology and functional impairment. Functional decline occurs early in the course of schizophrenia, and the symptoms that emerge during the prodromal stage may derail the normal adolescent neurodevelopment. Both first-episode psychosis and the prodrome may be opportunities to forestall neurodegeneration. Unfortunately, people with schizophrenia often experience a long duration of untreated psychosis. Treatment of first-episode psychosis with antipsychotic agents shows robust response. However, early-stage patients have very high rates of medication noncompliance. Treatment in the prodrome may offer the best chance to delay the onset of illness, mitigate its severity after onset, or even prevent onset of symptoms entirely. Nonpharmacologic treatments during the prodrome, such as education, treatment for substance use, and cognitive-behavioral therapy, are low-risk interventions that are potentially beneficial. Pharmacologic interventions during the prodrome are also effective in delaying onset of illness, but carry the risk of adversely affecting patients who are false positives for prodromal schizophrenia.

In this Expert Roundtable Supplement, Jeffrey A. Lieberman, MD, provides an overview of the neurobiological basis of neurodegeneration and the concept of neuroprotection. Next, Peter F. Buckley, MD, reviews the importance of first-episode psychosis, including duration of untreated illness and medication adherence. Finally, Diana O. Perkins, MD, MPH, reviews treatment strategies for prodromal schizophrenia.

Type
Research Article
Information
CNS Spectrums , Volume 12 , Issue S18 , 2007 , pp. 1 - 16
Copyright
Copyright © Cambridge University Press 2007

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Lieberman, JA, Perkins, D, Belger, A, et al.The early stages of schizophrenia: speculations on pathogenesis, pathophysiology, and therapeutic approaches. Biol Psychiatry. 2001;50(11):884–897.Google Scholar
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.Google Scholar
3.Lewis, DA, Austin, MC, Pierri, JN, et al.Decreased glutamic acid decarboxylase67 messenger RNA expression in a subset of prefrontal cortical gamma-aminobutyricacid neurons in subjects with schizophrenia. Arch Gen Psychiatry. 2000;57(3):237–245.Google Scholar
4.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; 161:742–744.Google Scholar
5.Margolis, RL, Chuang, DM, Post, RM. Programmed cell death: implications for neuropsychiatric disorders. Biol Psychiatry. 1994;35(12):946–956.CrossRefGoogle ScholarPubMed
6.Akbarian, S, Kim, JJ, Potkin, SG, Hetrick, WP, Bunney, WE, Jones, EG. Maldistribution of interstitial neurons in prefrontal white matter of the brains of schizophrenic patients. Arch Gen Psychiatry. 1996;53(5):425–436.CrossRefGoogle ScholarPubMed
7.Woods, BT. Is schizophrenia a progressive neurodevelopmental disorder? Toward a unitary pathogenetic mechanism. Am J Psychiatry. 1998;155(12):1661–1670.Google Scholar
8.Jarskog, LF, Gilmore, JH, Selinger, ES, Lieberman, JA. Cortical bcl-2 protein expression and apoptotic regulation in schizophrenia. Biol Psychiatry. 2000;48(7):641–650.CrossRefGoogle ScholarPubMed
9.Manji, HK, Duman, RS. Impairments of neuroplasticity and cellular resilience in severe mood disorders: implications for the development of novel therapeutics. Psychopharmacol Bull. 2001;35(2):5–49.Google Scholar
1.Marshall, M, Lewis, S, Lockwood, A, Drake, R, Jones, P, Croudace, T. Association between duration of untreated psychosis and outcome in cohorts of first-episode patients: a systematic review. Arch Gen Psychiatry. 2005;62(9):975–983.Google Scholar
2.Menezes, NM, Arenovich, T, Zipursky, RB. A systematic review of longitudinal outcome studies of first-episode psychosis. Psychol Med. 2006;36(10):1349–1362.Google Scholar
3.Emsley, RA. Risperidone in the treatment of first-episode psychotic patients: a double-blind multicenter study. Risperidone Working Group. Schizophr Bull. 1999;25(4):721–729.Google Scholar
4.Lieberman, JA, Tollefson, G, Tohen, M, et al.Comparative efficacy and safety of atypical and conventional antipsychotic drugs in first-episode psychosis: a randomized, double-blind trial of olanzapine versus haloperidol. Am J Psychiatry. 2003;160(8):1396–1404.CrossRefGoogle ScholarPubMed
5.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.Google Scholar
6.Schooler, N, Rabinowitz, J, Davidson, M, et al.Risperidone and haloperidol in first-episode psychosis: a long-term randomized trial. Am J Psychiatry. 2005;162(5):947–953.CrossRefGoogle ScholarPubMed
7.McEvoy, JP, Lieberman, JA, Perkins, DO, et al.Efficacy and tolerability of olanzapine, quetiapine, and risperidone in the treatment of early psychosis: a randomized, double-blind 52-week comparison. Am J Psychiatry. 2007;164(7):1050–1060.CrossRefGoogle ScholarPubMed
8.Lieberman, J, McEvoy, JP, Perkins, D, Hamer, RH. Comparison of atypicals in first-episode psychosis: a randomized, 52-week comparison of olanzapine, quetiapine, and risperidone. Eur Neuropsychopharmacol. 2005;15(Suppl 3):S526.Google Scholar
9.Marx, CE. Comparison of atypicals in first-episode psychosis (CAFE): a randomized, double-blind, 52-week comparison of olanzapine, quetiapine, and risperidone. Paper presented at: 8th World Congress of Biological Psychiatry; June 28-July 3, 2005; Vienna, Austria.Google Scholar
10.Robinson, DG, Woerner, MG, Alvir, JM, et al.Predictors of treatment response from a first episode of schizophrenia or schizoaffective disorder. Am J Psychiatry. 1999;156(4):544–549.Google Scholar
11.Perkins, DO, Johnson, JL, Hamer, RM, et al.Predictors of antipsychotic medication adherence in patients recovering from a first psychotic episode. Schizophr Res. 2006;83(1):53–63.Google Scholar
12.Lacro, JP, Dunn, LB, Dolder, CR, Leckband, SG, Jeste, DV. Prevalence of and risk factors for medication nonadherence in patients with schizophrenia: a comprehensive review of recent literature. J Clin Psychiatry. 2002;63(10):892–909.Google Scholar
13.Buckley, PF, Wirshing, DA, Pierre, J, Bushen, P, Resnick, S, Wishing, SC. Lack of insight and treatment adherence in schizophrenia. CNS Drugs. 2007;21:129–141.Google Scholar
1.Addington, J, Cadenhead, KS, Cannon, TD, et al.North American prodrome longitudinal study: a collaborative multisite approach to prodromal schizophrenia research. Schizophr Bull. 2007;33(3):665–672.Google Scholar
2.Keefe, RS, Perkins, DO, Gu, H, Zipursky, RB, Christensen, BK, Lieberman, JA. A longitudinal study of neurocognitive function in individuals at-risk for psychosis. Schizophr Res. 2006;88(1-3):26–35.CrossRefGoogle ScholarPubMed
3.Niendam, TA, Bearden, CE, Johnson, JK, et al.Neurocognitive performance and functional disability in the psychosis prodrome. Schizophr Res. 2006;84(1):100–111.Google Scholar
4.Spencer, MD, Moorhead, TW, McIntosh, AM, et al.Grey matter correlates of early psychotic symptoms in adolescents at enhanced risk of psychosis: a voxel-based study. Neuroimage. 2007;35(3):1181–1191.CrossRefGoogle ScholarPubMed
5.Hall, J, Whalley, HC, Job, DE, et al.A neuregulin 1 variant associated with abnormal cortical function and psychotic symptoms. Nat Neurosci. 2006;9(12):1477–1478.Google Scholar
6.McGorry, PD, Yung, AR, Phillips, LJ, et al.Randomized controlled trial of interventions designed to reduce the risk of progression to first-episode psychosis in a clinical sample with subthreshold symptoms. Arch Gen Psychiatry. 2002;59(10):921–928.CrossRefGoogle Scholar
7.McGlashan, TH, Zipursky, RB, Perkins, D, et al.Randomized, double-blind trial of olanzapine versus placebo in patients prodromally symptomatic for psychosis. Am J Psychiatry. 2006;163(5):790–799.Google Scholar
8.Morrison, AP, French, P, Walford, L, et al.Cognitive therapy for the prevention of psychosis in people at ultra-high risk: randomised controlled trial. Br J Psychiatry. 2004;185:291–297.Google Scholar
1.Amminger, GP, Schafer, MR. Indicated prevention with omega-3 fatty acids in adolescents at ultra high risk for psychosis-rationale, methods, and 3-months outcome. Schizophr Res. 2006;86(suppl):S97.Google Scholar
2.Woods, SW, Walsh, B, Pearlson, GD, et al.Glycine treatment of prodromal symptoms. Schizophr Res. 2006;86(suppl):S7.Google Scholar
3.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.Google Scholar