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Neuropsychological differences between treatment-resistant and treatment-responsive schizophrenia: a meta-analysis

Antipsychotic treatment resistance affects up to a third of individuals with schizophrenia. Of those affected, 70–84% are reported to be treatment resistant from the outset. This raises the possibility that the neurobiological mechanisms of treatment resistance emerge before the onset of psychosis a...

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Autores principales: Millgate, Edward, Hide, Olga, Lawrie, Stephen M, Murray, Robin M, MacCabe, James H, Kravariti, Eugenia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cambridge University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8711103/
https://www.ncbi.nlm.nih.gov/pubmed/36415088
http://dx.doi.org/10.1017/S0033291721004128
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author Millgate, Edward
Hide, Olga
Lawrie, Stephen M
Murray, Robin M
MacCabe, James H
Kravariti, Eugenia
author_facet Millgate, Edward
Hide, Olga
Lawrie, Stephen M
Murray, Robin M
MacCabe, James H
Kravariti, Eugenia
author_sort Millgate, Edward
collection PubMed
description Antipsychotic treatment resistance affects up to a third of individuals with schizophrenia. Of those affected, 70–84% are reported to be treatment resistant from the outset. This raises the possibility that the neurobiological mechanisms of treatment resistance emerge before the onset of psychosis and have a neurodevelopmental origin. Neuropsychological investigations can offer important insights into the nature, origin and pathophysiology of treatment-resistant schizophrenia (TRS), but methodological limitations in a still emergent field of research have obscured the neuropsychological discriminability of TRS. We report on the first systematic review and meta-analysis to investigate neuropsychological differences between TRS patients and treatment-responsive controls across 17 published studies (1864 participants). Five meta-analyses were performed in relation to (1) executive function, (2) general cognitive function, (3) attention, working memory and processing speed, (4) verbal memory and learning, and (5) visual−spatial memory and learning. Small-to-moderate effect sizes emerged for all domains. Similarly to previous comparisons between unselected, drug-naïve and first-episode schizophrenia samples v. healthy controls in the literature, the largest effect size was observed in verbal memory and learning [dl = −0.53; 95% confidence interval (CI) −0.29 to −0.76; z = 4.42; p < 0.001]. A sub-analysis of language-related functions, extracted from across the primary domains, yielded a comparable effect size (dl = −0.53, 95% CI −0.82 to −0.23; z = 3.45; p < 0.001). Manipulating our sampling strategy to include or exclude samples selected for clozapine response did not affect the pattern of findings. Our findings are discussed in relation to possible aetiological contributions to TRS.
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spelling pubmed-87111032022-01-07 Neuropsychological differences between treatment-resistant and treatment-responsive schizophrenia: a meta-analysis Millgate, Edward Hide, Olga Lawrie, Stephen M Murray, Robin M MacCabe, James H Kravariti, Eugenia Psychol Med Review Article Antipsychotic treatment resistance affects up to a third of individuals with schizophrenia. Of those affected, 70–84% are reported to be treatment resistant from the outset. This raises the possibility that the neurobiological mechanisms of treatment resistance emerge before the onset of psychosis and have a neurodevelopmental origin. Neuropsychological investigations can offer important insights into the nature, origin and pathophysiology of treatment-resistant schizophrenia (TRS), but methodological limitations in a still emergent field of research have obscured the neuropsychological discriminability of TRS. We report on the first systematic review and meta-analysis to investigate neuropsychological differences between TRS patients and treatment-responsive controls across 17 published studies (1864 participants). Five meta-analyses were performed in relation to (1) executive function, (2) general cognitive function, (3) attention, working memory and processing speed, (4) verbal memory and learning, and (5) visual−spatial memory and learning. Small-to-moderate effect sizes emerged for all domains. Similarly to previous comparisons between unselected, drug-naïve and first-episode schizophrenia samples v. healthy controls in the literature, the largest effect size was observed in verbal memory and learning [dl = −0.53; 95% confidence interval (CI) −0.29 to −0.76; z = 4.42; p < 0.001]. A sub-analysis of language-related functions, extracted from across the primary domains, yielded a comparable effect size (dl = −0.53, 95% CI −0.82 to −0.23; z = 3.45; p < 0.001). Manipulating our sampling strategy to include or exclude samples selected for clozapine response did not affect the pattern of findings. Our findings are discussed in relation to possible aetiological contributions to TRS. Cambridge University Press 2022-01 2021-11-01 /pmc/articles/PMC8711103/ /pubmed/36415088 http://dx.doi.org/10.1017/S0033291721004128 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited.
spellingShingle Review Article
Millgate, Edward
Hide, Olga
Lawrie, Stephen M
Murray, Robin M
MacCabe, James H
Kravariti, Eugenia
Neuropsychological differences between treatment-resistant and treatment-responsive schizophrenia: a meta-analysis
title Neuropsychological differences between treatment-resistant and treatment-responsive schizophrenia: a meta-analysis
title_full Neuropsychological differences between treatment-resistant and treatment-responsive schizophrenia: a meta-analysis
title_fullStr Neuropsychological differences between treatment-resistant and treatment-responsive schizophrenia: a meta-analysis
title_full_unstemmed Neuropsychological differences between treatment-resistant and treatment-responsive schizophrenia: a meta-analysis
title_short Neuropsychological differences between treatment-resistant and treatment-responsive schizophrenia: a meta-analysis
title_sort neuropsychological differences between treatment-resistant and treatment-responsive schizophrenia: a meta-analysis
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8711103/
https://www.ncbi.nlm.nih.gov/pubmed/36415088
http://dx.doi.org/10.1017/S0033291721004128
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