Treatment-resistant schizophrenia (TRS) impacts roughly one-third of individuals diagnosed with schizophrenia, with 70-84% demonstrating resistance to treatment from the onset. A comprehensive systematic review and meta-analysis, including 17 studies and 1864 participants, assessed neuropsychological differences between TRS patients and those responsive to treatment. This analysis spanned five cognitive domains—executive function, general cognitive function, attention and working memory, verbal memory and learning, and visual-spatial memory and learning.

Further studies into language-related functions across these domains showed significant deficits among TRS patients compared to those who are treatment-responsive, with effect sizes echoing those seen in verbal memory. These deficits remained consistent across analyses, regardless of adjustments for clozapine response. This research highlights the extensive cognitive impairments associated with TRS and suggests that these deficits might be integral to the neurodevelopmental underpinnings of the disorder. Recognizing these neuropsychological patterns helps delineate TRS as possibly a distinct or more severe variant of psychosis.

Reference: Millgate E, Hide O, Lawrie SM, Murray RM, MacCabe JH, Kravariti E. Neuropsychological differences between treatment-resistant and treatment-responsive schizophrenia: a meta-analysis. Psychol Med. 2022 Jan;52(1):1-13. doi: 10.1017/S0033291721004128. Epub 2021 Nov 1. PMID: 36415088; PMCID: PMC8711103.