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Pseudospecificity of Negative Symptom Improvement in the Schizophrenia Spectrum: A Meta-Analytic Investigation of Associations with Depression, Quality of Life and Extrapyramidal Symptoms

D'Imperio, Aldo LU orcid ; Damiani, Stefano ; Stefanelli, Riccardo ; Patron, Sara ; Santilli, Fabrizio and Fusar-Poli, Paolo (2026) 2026 Annual Congress of the Schizophrenia International Research Society (SIRS)
Abstract
Negative symptoms are among the most disabling dimensions of schizophrenia-spectrum disorders and are strongly associated with poorer long-term functioning. However, their interpretation in treatment trials remains challenging because apparent improvement in negative symptoms may partly reflect change in other domains, including depressive symptoms, quality of life, or secondary phenomena such as medication-related motor side effects. We examined whether improvement in negative symptoms across randomized controlled trials in schizophrenia-spectrum disorders was associated with parallel change in depressive symptoms, quality of life, and extrapyramidal symptoms. We performed a meta-synthesis of randomized controlled trials identified in Web... (More)
Negative symptoms are among the most disabling dimensions of schizophrenia-spectrum disorders and are strongly associated with poorer long-term functioning. However, their interpretation in treatment trials remains challenging because apparent improvement in negative symptoms may partly reflect change in other domains, including depressive symptoms, quality of life, or secondary phenomena such as medication-related motor side effects. We examined whether improvement in negative symptoms across randomized controlled trials in schizophrenia-spectrum disorders was associated with parallel change in depressive symptoms, quality of life, and extrapyramidal symptoms. We performed a meta-synthesis of randomized controlled trials identified in Web of Science and PsycINFO from inception to December 2024. Associations between percentage change in negative symptoms and companion domains were analysed at arm level using Spearman correlations. Across 129 trials (274 arms), improvement in negative symptoms was significantly associated with improvement in depressive symptoms (ρ = 0.359, p < 0.001). Across 69 trials (145 arms), improvement in negative symptoms was also associated with improvement in quality of life (ρ = 0.230, p = 0.006). No meaningful association was observed with extrapyramidal symptoms across 69 trials (160 arms; ρ = -0.082, p = 0.330). The findings support the presence of pseudospecificity in schizophrenia-spectrum trials and highlight the importance of distinguishing primary from secondary negative symptoms. (Less)
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author
; ; ; ; and
organization
publishing date
type
Contribution to conference
publication status
published
subject
keywords
schizophrenia, meta-analysis, quality of life, pseudopsecificity, depression, negative symptoms
pages
1 pages
conference name
2026 Annual Congress of the Schizophrenia International Research Society (SIRS)
conference location
Florence, Italy
conference dates
2026-03-25 - 2026-03-29
DOI
10.5281/zenodo.23121801
language
English
LU publication?
yes
id
5b76bf5b-620b-4294-ab35-908e5bfc9ca8
date added to LUP
2026-10-03 16:25:25
date last changed
2026-10-05 08:04:48
@misc{5b76bf5b-620b-4294-ab35-908e5bfc9ca8,
  abstract     = {{Negative symptoms are among the most disabling dimensions of schizophrenia-spectrum disorders and are strongly associated with poorer long-term functioning. However, their interpretation in treatment trials remains challenging because apparent improvement in negative symptoms may partly reflect change in other domains, including depressive symptoms, quality of life, or secondary phenomena such as medication-related motor side effects. We examined whether improvement in negative symptoms across randomized controlled trials in schizophrenia-spectrum disorders was associated with parallel change in depressive symptoms, quality of life, and extrapyramidal symptoms. We performed a meta-synthesis of randomized controlled trials identified in Web of Science and PsycINFO from inception to December 2024. Associations between percentage change in negative symptoms and companion domains were analysed at arm level using Spearman correlations. Across 129 trials (274 arms), improvement in negative symptoms was significantly associated with improvement in depressive symptoms (ρ = 0.359, p &lt; 0.001). Across 69 trials (145 arms), improvement in negative symptoms was also associated with improvement in quality of life (ρ = 0.230, p = 0.006). No meaningful association was observed with extrapyramidal symptoms across 69 trials (160 arms; ρ = -0.082, p = 0.330). The findings support the presence of pseudospecificity in schizophrenia-spectrum trials and highlight the importance of distinguishing primary from secondary negative symptoms.}},
  author       = {{D'Imperio, Aldo and Damiani, Stefano and Stefanelli, Riccardo and Patron, Sara and Santilli, Fabrizio and Fusar-Poli, Paolo}},
  keywords     = {{schizophrenia; meta-analysis; quality of life; pseudopsecificity; depression; negative symptoms}},
  language     = {{eng}},
  month        = {{03}},
  title        = {{Pseudospecificity of Negative Symptom Improvement in the Schizophrenia Spectrum: A Meta-Analytic Investigation of Associations with Depression, Quality of Life and Extrapyramidal Symptoms}},
  url          = {{https://lup.lub.lu.se/search/files/262287028/Poster_SIRS_2026_Aldo_D_Imperio.pdf}},
  doi          = {{10.5281/zenodo.23121801}},
  year         = {{2026}},
}