TY - JOUR
T1 - Neuropsychological differences between treatment-resistant and treatment-responsive schizophrenia: a meta-analysis.
AU - Millgate, Edward
AU - Hide, Olga
AU - Lawrie, Stephen
AU - Murray, Robin
AU - Kravariti, Jenny
N1 - Funding Information:
EM's PhD is funded by the MRC-doctoral training partnership studentship in Biomedical Sciences at King's College London. JHM, RMM & EK are part funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. In the past 3 years, S.M.L. has received personal support from Sunovion. The views expressed are those of the authors and not necessarily those of the NHS, the MRC, the NIHR, Sunovion, or the Department of Health.
Publisher Copyright:
Copyright © The Author(s), 2021. Published by Cambridge University Press
PY - 2022/1/1
Y1 - 2022/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85118986258&partnerID=8YFLogxK
U2 - 10.1017/S0033291721004128
DO - 10.1017/S0033291721004128
M3 - Article
SN - 0033-2917
VL - 52
JO - Psychological medicine
JF - Psychological medicine
IS - 1
ER -