Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Psychiatry
Published in: BMC Psychiatry 1/2013

Open Access 01-12-2013 | Research article

The longitudinal interplay between negative and positive symptom trajectories in patients under antipsychotic treatment: a post hoc analysis of data from a randomized, 1-year pragmatic trial

Authors: Lei Chen, Joseph A Johnston, Bruce J Kinon, Virginia Stauffer, Paul Succop, Tiago R Marques, Haya Ascher-Svanum

Published in: BMC Psychiatry | Issue 1/2013

Login to get access

Abstract

Background

Schizophrenia is a highly heterogeneous disorder with positive and negative symptoms being characteristic manifestations of the disease. While these two symptom domains are usually construed as distinct and orthogonal, little is known about the longitudinal pattern of negative symptoms and their linkage with the positive symptoms. This study assessed the temporal interplay between these two symptom domains and evaluated whether the improvements in these symptoms were inversely correlated or independent with each other.

Methods

This post hoc analysis used data from a multicenter, randomized, open-label, 1-year pragmatic trial of patients with schizophrenia spectrum disorder who were treated with first- and second-generation antipsychotics in the usual clinical settings. Data from all treatment groups were pooled resulting in 399 patients with complete data on both the negative and positive subscale scores from the Positive and Negative Syndrome Scale (PANSS). Individual-based growth mixture modeling combined with interplay matrix was used to identify the latent trajectory patterns in terms of both the negative and positive symptoms. Pearson correlation coefficients were calculated to examine the relationship between the changes of these two symptom domains within each combined trajectory pattern.

Results

We identified four distinct negative symptom trajectories and three positive symptom trajectories. The trajectory matrix formed 11 combined trajectory patterns, which evidenced that negative and positive symptom trajectories moved generally in parallel. Correlation coefficients for changes in negative and positive symptom subscale scores were positive and statistically significant (P < 0.05). Overall, the combined trajectories indicated three major distinct patterns: 1) dramatic and sustained early improvement in both negative and positive symptoms (n = 70, 18%), 2) mild and sustained improvement in negative and positive symptoms (n = 237, 59%), and 3) no improvement in either negative or positive symptoms (n = 82, 21%).

Conclusions

This study of symptom trajectories over 1 year shows that changes in negative and positive symptoms were neither inversely nor independently related with each other. The positive association between these two symptom domains supports the notion that different symptom domains in schizophrenia may depend on each other through a unified upstream pathological disease process.
Appendix
Available only for authorised users
Literature
1.
Tsuang MT, Lyons MJ, Faraone SV: Heterogeneity of schizophrenia. Conceptual models and analytic strategies. Br J Psychiatry. 1990, 156: 17-26. 10.1192/bjp.156.1.17.CrossRefPubMed
2.
McGrath J: Dissecting the heterogeneity of schizophrenia outcomes. Schizophr Bull. 2008, 34 (2): 247-248.CrossRefPubMed
3.
Case M, Stauffer VL, Ascher-Svanum H, Conley R, Kapur S, Kane JM, Kollack-Walker S, Jacob J, Kinon BJ: The heterogeneity of antipsychotic response in the treatment of schizophrenia. Psychol Med. 2011, 41 (06): 1291-1300. 10.1017/S0033291710001893.CrossRefPubMed
4.
Levine SZ, Leucht S: Elaboration on the early-onset hypothesis of antipsychotic drug action: treatment response trajectories. Biol Psychiatry. 2010, 68 (1): 86-92. 10.1016/j.biopsych.2010.01.012.CrossRefPubMed
5.
Levine SZ, Rabinowitz J, Faries D, Lawson AH, Ascher-Svanum H: Treatment response trajectories and antipsychotic medications: examination of up to 18 months of treatment in the CATIE chronic schizophrenia trial. Schizophr Res. 2012, 137 (1–3): 141-146.CrossRefPubMed
6.
Levine SZ, Rabinowitz J, Case M, Ascher-Svanum H: Treatment response trajectories and their antecedents in recent-onset psychosis: a 2-year prospective study. J Clin Psychopharmacol. 2010, 30 (4): 446-449. 10.1097/JCP.0b013e3181e68e80.CrossRefPubMed
7.
Levine SZ, Rabinowitz J: Trajectories and antecedents of treatment response over time in early-episode psychosis. Schizophr Bull. 2010, 36 (3): 624-632. 10.1093/schbul/sbn120.CrossRefPubMed
8.
Levine SZ, Lurie I, Kohn R, Levav I: Trajectories of the course of schizophrenia: from progressive deterioration to amelioration over three decades. Schizophr Res. 2011, 126 (1–3): 184-191.CrossRefPubMed
9.
First MB: Diagnostic and statistical manual of mental disorders 4th Ed. (DSM-IV-TR™, 2000), 4 edn. 2000, American Psychiatric Association: Washington, DC
10.
Javitt DC, Zukin SR: Recent advances in the phencyclidine model of schizophrenia. Am J Psychiatry. 1991, 148 (10): 1301-1308.CrossRefPubMed
11.
Buchanan RW, Breier A, Kirkpatrick B, Ball P, Carpenter WT: Positive and negative symptom response to clozapine in schizophrenic patients with and without the deficit syndrome. Am J Psychiatry. 1998, 155 (6): 751-760.PubMed
12.
Kane JM, Marder SR, Schooler NR, Wirshing WC, Umbricht D, Baker RW, Wirshing DA, Safferman A, Ganguli R, McMeniman M, et al: Clozapine and haloperidol in moderately refractory schizophrenia: a 6-month randomized and double-blind comparison. Arch Gen Psychiatry. 2001, 58 (10): 965-972. 10.1001/archpsyc.58.10.965.CrossRefPubMed
13.
Kirkpatrick B, Fenton WS, Carpenter WT, Marder SR: The NIMH-MATRICS consensus statement on negative symptoms. Schizophr Bull. 2006, 32 (2): 214-219. 10.1093/schbul/sbj053.CrossRefPubMedPubMedCentral
14.
Levine BG, Stone JE, Kohlmeyer A: Fast analysis of molecular dynamics trajectories with graphics processing units-radial distribution function Histogramming. J Comput Phys. 2011, 230 (9): 3556-3569. 10.1016/j.jcp.2011.01.048.CrossRefPubMedPubMedCentral
15.
Lyne J, O’Donoghue B, Owens E, Renwick L, Madigan K, Kinsella A, Clarke M, Turner N, O’Callaghan E: Prevalence of item level negative symptoms in first episode psychosis diagnoses. Schizophr Res. 2012, 135 (1–3): 128-133.CrossRefPubMed
16.
Addington J, Addington D: Positive and negative symptoms of schizophrenia. Their course and relationship over time. Schizophr Res. 1991, 5 (1): 51-59. 10.1016/0920-9964(91)90053-T.CrossRefPubMed
17.
Andreasen NC, Olsen SA, Dennert JW, Smith MR: Ventricular enlargement in schizophrenia: relationship to positive and negative symptoms. Am J Psychiatry. 1982, 139 (3): 297-302.CrossRefPubMed
18.
Carpenter WT, Bartko JJ, Carpenter CL, Strauss JS: Another view of schizophrenia subtypes. A report from the international pilot study of schizophrenia. Arch Gen Psychiatry. 1976, 33 (4): 508-516. 10.1001/archpsyc.1976.01770040068012.CrossRefPubMed
19.
Andreasen NC: Negative symptoms in schizophrenia. Definition and reliability. Arch Gen Psychiatry. 1982, 39 (7): 784-788. 10.1001/archpsyc.1982.04290070020005.CrossRefPubMed
20.
21.
Goghari VM, Sponheim SR, MacDonald AW: The functional neuroanatomy of symptom dimensions in schizophrenia: a qualitative and quantitative review of a persistent question. Neurosci Biobehav Rev. 2010, 34 (3): 468-486. 10.1016/j.neubiorev.2009.09.004.CrossRefPubMed
22.
Guelfi GP, Faustman WO, Csernansky JG: Independence of positive and negative symptoms in a population of schizophrenic patients. J Nerv Ment Dis. 1989, 177 (5): 285-290. 10.1097/00005053-198905000-00006.CrossRefPubMed
23.
24.
Tunis SL, Faries DE, Nyhuis AW, Kinon BJ, Ascher-Svanum H, Aquila R: Cost-effectiveness of olanzapine as first-line treatment for schizophrenia: results from a randomized, open-label, 1-year trial. Value Health. 2006, 9 (2): 77-89. 10.1111/j.1524-4733.2006.00083.x.CrossRefPubMed
25.
Kay SR, Fiszbein A, Opler LA: The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987, 13 (2): 261-276. 10.1093/schbul/13.2.261.CrossRefPubMed
26.
Kay SR, Opler LA, Lindenmayer JP: Reliability and validity of the positive and negative syndrome scale for schizophrenics. Psychiatry Res. 1988, 23 (1): 99-110. 10.1016/0165-1781(88)90038-8.CrossRefPubMed
27.
Santor DA, Ascher-Svanum H, Lindenmayer JP, Obenchain RL: Item response analysis of the positive and negative syndrome scale. BMC Psychiatry. 2007, 7: 66-10.1186/1471-244X-7-66.CrossRefPubMedPubMedCentral
28.
Cutler AJ, Kalali AH, Weiden PJ, Hamilton J, Wolfgang CD: Four-week, double-blind, placebo- and ziprasidone-controlled trial of iloperidone in patients with acute exacerbations of schizophrenia. J Clin Psychopharmacol. 2008, 28 (2 Suppl 1): S20-S28.CrossRefPubMed
29.
Kane JM, Assuncao-Talbott S, Eudicone JM, Pikalov A, Whitehead R, Crandall DT: The efficacy of aripiprazole in the treatment of multiple symptom domains in patients with acute schizophrenia: a pooled analysis of data from the pivotal trials. Schizophr Res. 2008, 105 (1–3): 208-215.CrossRefPubMed
30.
Nakamura M, Ogasa M, Guarino J, Phillips D, Severs J, Cucchiaro J, Loebel A: Lurasidone in the treatment of acute schizophrenia: a double-blind, placebo-controlled trial. J Clin Psychiatry. 2009, 70 (6): 829-836. 10.4088/JCP.08m04905.CrossRefPubMed
31.
Muthen B, Muthen L: Mplus - Statistical analysis with latent variables - user’s guide. 2007, Muthen and Muthen: Los Angeles, 5
32.
Muthen B: Latent variable mixture modeling. New developments and techniques in structural equation modeling. Edited by: Marcoulides GA, Schumacker RE. 2001, Mahwah, NJ: Lawrence Erlbaum Associates, 1-33.
33.
Bauer DJ, Curran PJ: Distributional assumptions of growth mixture models: implications for overextraction of latent trajectory classes. Psychol Methods. 2003, 8 (3): 338-363.CrossRefPubMed
34.
Pearson WH: Estimation of a correlation coefficient from an uncertainty measure. Psychometrika. 1966, 31 (3): 421-433. 10.1007/BF02289473.CrossRefPubMed
35.
Gueorguieva R, Mallinckrodt C, Krystal JH: Trajectories of depression severity in clinical trials of duloxetine: insights into antidepressant and placebo responses. Arch Gen Psychiatry. 2011, 68 (12): 1227-1237. 10.1001/archgenpsychiatry.2011.132.CrossRefPubMedPubMedCentral
36.
Marques TR, Arenovich T, Agid O, Sajeev G, Muthen B, Chen L, Kinon BJ, Kapur S: The different trajectories of antipsychotic response: antipsychotics versus placebo. Psychol Med. 2011, 41 (7): 1481-1488. 10.1017/S0033291710002035.CrossRefPubMed
37.
Stauffer V, Case M, Kollack-Walker S, Ascher-Svanum H, Ball T, Kapur S, Kinon BJ: Trajectories of response to treatment with atypical antipsychotic medication in patients with schizophrenia pooled from 6 double-blind, randomized clinical trials. Schizophr Res. 2011, 130 (1–3): 11-19.CrossRefPubMed
38.
Crow TJ: The two-syndrome concept: origins and current status. Schizophr Bull. 1985, 11 (3): 471-486. 10.1093/schbul/11.3.471.CrossRefPubMed
39.
Howes OD, Kapur S: The dopamine hypothesis of schizophrenia: version III–the final common pathway. Schizophr Bull. 2009, 35 (3): 549-562. 10.1093/schbul/sbp006.CrossRefPubMedPubMedCentral
40.
Carpenter WT, Heinrichs DW, Wagman AM: Deficit and nondeficit forms of schizophrenia: the concept. Am J Psychiatry. 1988, 145 (5): 578-583.CrossRefPubMed
41.
Tollefson GD, Sanger TM: Negative symptoms: a path analytic approach to a double-blind, placebo- and haloperidol-controlled clinical trial with olanzapine. Am J Psychiatry. 1997, 154 (4): 466-474.CrossRefPubMed
42.
Stauffer VL, Song G, Kinon BJ, Ascher-Svanum H, Chen L, Feldman PD, Conley RR: Responses to antipsychotic therapy among patients with schizophrenia or schizoaffective disorder and either predominant or prominent negative symptoms. Schizophr Res. 2012, 134 (2–3): 195-201.CrossRefPubMed
43.
Kinon BJ, Kane JM, Chakos M, Munne R: Possible predictors of neuroleptic-resistant schizophrenic relapse: influence of negative symptoms and acute extrapyramidal side effects. Psychopharmacol Bull. 1993, 29 (3): 365-369.PubMed
44.
Chen J, Ascher-Svanum H, Nyhuis AW, Case MG, Phillips GA, Schuh KJ, Hoffmann VP: Reasons for continuing or discontinuing olanzapine in the treatment of schizophrenia from the perspectives of patients and clinicians. Patient Pref Adher. 2011, 5: 547-554.
45.
Velligan DI, Alphs L, Lancaster S, Morlock R, Mintz J: Association between changes on the Negative Symptom Assessment scale (NSA-16) and measures of functional outcome in schizophrenia. Psychiatry Res. 2009, 169 (2): 97-100. 10.1016/j.psychres.2008.10.009.CrossRefPubMed
46.
Beasley CM, Sanger T, Satterlee W, Tollefson G, Tran P, Hamilton S: Olanzapine versus placebo: results of a double-blind, fixed-dose olanzapine trial. Psychopharmacology (Berl). 1996, 124 (1–2): 159-167.CrossRef
47.
Beasley CM, Tollefson G, Tran P, Satterlee W, Sanger T, Hamilton S: Olanzapine versus placebo and haloperidol: acute phase results of the North American double-blind olanzapine trial. Neuropsychopharmacology. 1996, 14 (2): 111-123. 10.1016/0893-133X(95)00069-P.CrossRefPubMed
48.
Patil ST, Zhang L, Martenyi F, Lowe SL, Jackson KA, Andreev BV, Avedisova AS, Bardenstein LM, Gurovich IY, Morozova MA, et al: Activation of mGlu2/3 receptors as a new approach to treat schizophrenia: a randomized phase 2 clinical trial. Nat Med. 2007, 13 (9): 1102-1107. 10.1038/nm1632.CrossRefPubMed
49.
Arango C, Buchanan RW, Kirkpatrick B, Carpenter WT: The deficit syndrome in schizophrenia: implications for the treatment of negative symptoms. Eur Psychiatry. 2004, 19 (1): 21-26. 10.1016/j.eurpsy.2003.10.004.CrossRefPubMed
Metadata
Title
The longitudinal interplay between negative and positive symptom trajectories in patients under antipsychotic treatment: a post hoc analysis of data from a randomized, 1-year pragmatic trial
Authors
Lei Chen
Joseph A Johnston
Bruce J Kinon
Virginia Stauffer
Paul Succop
Tiago R Marques
Haya Ascher-Svanum
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Psychiatry / Issue 1/2013
Electronic ISSN: 1471-244X
DOI
https://doi.org/10.1186/1471-244X-13-320

Other articles of this Issue 1/2013

BMC Psychiatry 1/2013 Go to the issue

Research article

Predictors and impact of non-adherence in adults with attention-deficit/hyperactivity disorder receiving OROS methylphenidate: results from a randomized, placebo-controlled trial

Research article

Radically open-dialectical behavior therapy for adult anorexia nervosa: feasibility and outcomes from an inpatient program

Research article

Psychometric properties of the abbreviated version of the Scale to Assess Unawareness in Mental Disorder in schizophrenia

Research article

Schizotypy and personality profiles of Cluster A in a group of schizophrenic patients and their siblings

Research article

Attitudes towards the administration of long-acting antipsychotics: a survey of physicians and nurses

Review

Perplexities of treatment resistence in eating disorders