A novel way to quantify schizophrenia symptoms in clinical trials
Open accessAbstract
Background: A major problem in quantifying symptoms of schizophrenia is establishing a reliable distinction between enduring and dynamic aspects of psychopathology. This is critical for accurate diagnosis, monitoring and evaluating treatment effects in both clinical practice and trials. Materials and methods: We applied Generalizability Theory, a robust novel method to distinguish between dynamic and stable aspects of schizophrenia symptoms in the widely used Positive and Negative Symptom Scale (PANSS) using a longitudinal measurement design. The sample included 107 patients with chronic schizophrenia assessed using the PANSS at five time points over a 24‐week period during a multi‐site clinical trial of N‐Acetylcysteine as an add‐on to maintenance medication for the treatment of chronic schizophrenia. Results: The original PANSS and its three subscales demonstrated good reliability and generalizability of scores (G = 0.77‐0.93) across sample population and occasions making them suitable for assessment of psychosis risks and long‐lasting change following a treatment, while subscales of the five‐factor models appeared less reliable. The most enduring symptoms represented by the PANSS were poor attention, delusions, blunted affect and poor rapport. More dynamic symptoms with 40%‐50% of variance explained by patient transient state including grandiosity, preoccupation, somatic concerns, guilt feeling and hallucinatory behaviour. Conclusions: Identified dynamic symptoms are more amendable to change and should be the primary target of interventions aiming at effectively treating schizophrenia. Separating out the dynamic symptoms would increase assay sensitivity in trials, reduce the signal to noise ratio and increase the potential to detect the effects of novel therapies in clinical trials.
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Items in a psychometric measure reflect different aspects of a construct being measured, and investigating state variability of different items over time can provide meaningful information about which aspects of a construct are most dynamic over time.
“Items in a psychometric measure reflect different aspects of a construct being measured (e.g., resilience) and investigating (state) variability of different items over time can provide a meaningful information as to what aspects of a construct are the most dynamic over time (Medvedev etal., 2021).”
From Investigating state and trait aspects of resilience using Generalizability theory (2024) · cites this paper as Medvedev et al., 2021
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Cites
The Positive and Negative Syndrome Scale (PANSS) for schizophrenia.
Kay, S. R., Fiszbein, A., & Opler, L. A. (1987) · Schizophrenia Bulletin · doi:10.1093/schbul/13.2.261 · Cited by 21,378 · see citing works
The clinical global impressions scale: applying a research tool in clinical practice.
Busner, J., & Targum, S. D. (2007) · PubMed Central · Cited by 1,952 · see citing works
A catalogue of reporting guidelines for health research
Simera, I., Moher, D., Hoey, J., Schulz, K. F., & Altman, D. G. (2010) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.2009.02234.x · Cited by 1,047 · see citing works
Fusar‐Poli, P., Papanastasiou, E., Stahl, D. R., Rocchetti, M., Carpenter, W. T., Shergill, S. S., & McGuire, P. K. (2014) · Schizophrenia Bulletin · doi:10.1093/schbul/sbu170 · Cited by 686 · see citing works
Elements of Generalizability Theory
Brennan, R. L. (1992) · Medical Entomology and Zoology · Cited by 601 · see citing works
Psychometric properties of the Positive and Negative Syndrome Scale (PANSS) in schizophrenia
Peralta, V., & Cuesta, M. J. (1994) · Psychiatry Research · doi:10.1016/0165-1781(94)90093-0 · Cited by 583 · see citing works
van der Gaag, M., Hoffman, T. O., REMIJSEN, M., Hijman, R., DEHAAN, L., VANMEIJEL, B., VANHARTEN, P., Valmaggia, L., DEHERT, M., & CUIJPERS, A. (2006) · Schizophrenia Research · doi:10.1016/j.schres.2006.03.021 · Cited by 555 · see citing works
Berk, M., Copolov, D., Dean, O., Lu, K., Jeavons, S., Schapkaitz, I., Anderson-Hunt, M., Judd, F., Katz, F., Katz, P., et al. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.03.004 · Cited by 552 · see citing works
Self-citationA Longitudinal Study of Symptom Dimensions in Schizophrenia
Arndt, S. V. (1995) · Archives of General Psychiatry · doi:10.1001/archpsyc.1995.03950170026004 · Cited by 304 · see citing works
Validation of the State-Trait Distinction in Anxiety Research
Gaudry, E., Vagg, P., & Spielberger, C. D. (1975) · Multivariate Behavioral Research · doi:10.1207/s15327906mbr1003_6 · Cited by 260 · see citing works
Generalizability theory for the perplexed: A practical introduction and guide: AMEE Guide No. 68
Blöch, R., & Norman, G. R. (2012) · Medical Teacher · doi:10.3109/0142159x.2012.703791 · Cited by 248 · see citing works
Negative symptoms of schizophrenia: a problem that will not go away
Stahl, S. M., & Buckley, P. F. (2007) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.2006.00947.x · Cited by 195 · see citing works
Applying Generalizability Theory using EduG
Cardinet, J., Johnson, S., & Pini, G. (2011) · Routledge eBooks · doi:10.4324/9780203866948 · Cited by 187 · see citing works
What is being assessed and why it matters: The impact of transient error on trait research.
Chmielewski, M. S., & Watson, D. (2009) · Journal of Personality and Social Psychology · doi:10.1037/a0015618 · Cited by 175 · see citing works
Primary and persistent negative symptoms: Concepts, assessments and neurobiological bases
Mucci, A., Merlotti, E., Üçok, A., Aleman, A., & Galderisi, S. (2016) · Schizophrenia Research · doi:10.1016/j.schres.2016.05.014 · Cited by 141 · see citing works
Measuring Mindfulness: Applying Generalizability Theory to Distinguish between State and Trait
Medvedev, O. N., Krägeloh, C. U., Narayanan, A., & Siegert, R. J. (2017) · Mindfulness · doi:10.1007/s12671-017-0679-0 · Cited by 127 · see citing works
Self-citationVangeneugden, T., Laenen, A., Geys, H., Renard, D., & Molenberghs, G. (2005) · Biometrics · doi:10.1111/j.0006-341x.2005.031040.x · Cited by 104 · see citing works
Primary, Enduring Negative Symptoms: An Update on Research
Kirkpatrick, B. W., Mucci, A., & Galderisi, S. (2017) · Schizophrenia Bulletin · doi:10.1093/schbul/sbx064 · Cited by 104 · see citing works
Vispoel, W. P., Morris, C. A., & Kilinc, M. (2017) · Psychological Methods · doi:10.1037/met0000107 · Cited by 83 · see citing works
Do negative symptoms of schizophrenia change over time? A meta-analysis of longitudinal data
Savill, M., Banks, C., Khanom, H., & Priebe, S. (2014) · Psychological Medicine · doi:10.1017/s0033291714002712 · Cited by 72 · see citing works
Edgar, C. J., Blaettler, T., Bugarski‐Kirola, D., Scouiller, S. L., Garibaldi, G. M., & Marder, S. R. (2014) · Psychiatry Research · doi:10.1016/j.psychres.2014.04.009 · Cited by 40 · see citing works
Paterson, J., Medvedev, O. N., Sumich, A., Tautolo, E.-S., Krägeloh, C. U., Sisk, R., McNamara, R. K., Berk, M., Narayanan, A., & Siegert, R. J. (2018) · Journal of Affective Disorders · doi:10.1016/j.jad.2017.11.075 · Cited by 28 · see citing works
Self-citationSchennach-Wolff, R., Obermeier, M., Seemüller, F., Jäger, M., Schmauß, M., Laux, G., Pfeiffer, H., Naber, D., Schmidt, L., Gäebel, W., et al. (2010) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0b013e3181faf39b · Cited by 27 · see citing works
A latent class analysis of psychotic symptoms in the general population
Pignon, B., Peyre, H., Szöke, A., Geoffroy, P. A., Rolland, B., Jardri, R., Thomas, P., Vaïva, G., Roelandt, J.-L., Benradia, I., et al. (2017) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/0004867417744255 · Cited by 26 · see citing works
Khan, A., Yavorsky, W. C., Liechti, S., DiClemente, G., Rothman, B., Opler, M. G., DeFries, A., & Jovic, S. (2012) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0b013e3182776ebe · Cited by 21 · see citing works
Zhang, T., Xu, L., Tang, Y., Cui, H., Li, H., Wei, Y., Xu, Y., Jiang, L., Zhu, Y., Li, C., et al. (2017) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/0004867417712460 · Cited by 21 · see citing works
Pellicciari, A., Tedesco, P., & Chiodo, S. (2018) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/0004867417753551 · Cited by 1 · see citing works
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Investigating state and trait aspects of resilience using Generalizability theory
Child, L. E., & Medvedev, O. N. (2024) · Current Psychology · doi:10.1007/s12144-023-05072-4 · Cited by 23 · see citing works
“Items in a psychometric measure reflect different aspects of a construct being measured (e.g., resilience) and investigating (state) variability of different items over time can provide a meaningful information as to what aspects of a construct are the most dynamic over time (Medvedev et al., 2021).”
Self-citation
- Authors
- Medvedev, O. N., Berk, M., Dean, O. M., Brown, E., Sandham, M. H., Dipnall, J. F., McNamara, R. K., Sumich, A., Krägeloh, C. U., Narayanan, A., & Siegert, R. J.
- Affiliations
- Auckland University of Technology (NZ)
- Deakin University (AU)
- University of Cincinnati (US)
- Corresponding author
- Medvedev, Oleg N.
- ORCID
- Venue
- European Journal of Clinical Investigation
- Publisher
- Wiley
- Published
- 2020-09-19
- Volume
- 51
- Issue
- 3
- Pages
- e13398-e13398
- ISSN
- 0014-2972 (ISSN-L)
- 1365-2362
- PMC
- PMC7988538
- OpenAlex
- W3084316153
- Cited by
- 23
- References
- 27
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 2 · 2023: 3 · 2022: 5 · 2021: 5
- FWCI
- 2.37
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- European Journal of Clinical Investigation (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Nottingham Trent University's Institutional Repository (Nottingham Trent Repository) (acceptedVersion)
- Tuwhera (Auckland University of Technology) (submittedVersion, cc-by)
- Research Commons (University of Waikato) (submittedVersion, cc-by)
- Deakin Research Online (Deakin University) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by)
- Funders
- Royal Society Te Apārangi
- Medical Research Council
- National Health and Medical Research Council (1156072, 1059660)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Social Sciences › Decision Sciences › Management Science and Operations Research › Psychometric Methodologies and Testing
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Mental Health Research Topics
- Keywords
- schizophrenia, symptom quantification, generalizability theory, PANSS, chronic schizophrenia, N-acetylcysteine, longitudinal assessment, assay sensitivity, Big Five personality traits, delusions, hallucinations, blunted affect
- MeSH terms
- Acetylcysteine, Adolescent, Adult, Aged, Attention, Clinical Trials as Topic, Delusions, Female, Guilt, Hallucinations, Humans, Male, Middle Aged, Schizophrenia, Schizophrenic Psychology, Antipsychotic Agents, Randomized Controlled Trials as Topic, Free Radical Scavengers, Mood Disorders, Young Adult, Patient Outcome Assessment
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