Journal
PSYCHOLOGICAL MEDICINE
Volume 52, Issue 1, Pages 1-13Publisher
CAMBRIDGE UNIV PRESS
DOI: 10.1017/S0033291721004128
Keywords
treatment-resistant schizophrenia; neuropsychological deficits; verbal memory and learning; language functions; meta-analysis
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Funding
- MRC-doctoral training partnership studentship in Biomedical Sciences at King's College London
- National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust
- King's College London
- Sunovion
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This study systematically reviewed and meta-analyzed the neuropsychological differences between patients with treatment-resistant schizophrenia (TRS) and treatment-responsive controls. The results showed small-to-moderate effect sizes in all domains, with the largest effect size observed in verbal memory and learning.
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-naive 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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