Cross-sectional study comparing cognitive function in treatment responsive versus treatment non-responsive schizophrenia: evidence from the STRATA study

Abstract

Background70%–84% of individuals with antipsychotic treatment resistance show non-response from the first episode. Emerging cross-sectional evidence comparing cognitive profiles in treatment resistant schizophrenia to treatment-responsive schizophrenia has indicated that verbal memory and language functions may be more impaired in treatment resistance. We sought to confirm this finding by comparing cognitive performance between antipsychotic non-responders (NR) and responders (R) using a brief cognitive battery for schizophrenia, with a primary focus on verbal tasks compared against other measures of cognition.DesignCross-sectional.SettingThis cross-sectional study recruited antipsychotic treatment R and antipsychotic NR across four UK sites. Cognitive performance was assessed using the Brief Assessment of Cognition in Schizophrenia (BACS).ParticipantsOne hundred and six participants aged 18–65 years with a diagnosis of schizophrenia or schizophreniform disorder were recruited according to their treatment response, with 52 NR and 54 R cases.OutcomesComposite and subscale scores of cognitive performance on the BACS. Group (R vs NR) differences in cognitive scores were investigated using univariable and multivariable linear regressions adjusted for age, gender and illness duration.ResultsUnivariable regression models observed no significant differences between R and NR groups on any measure of the BACS, including verbal memory (ß=−1.99, 95% CI −6.63 to 2.66, p=0.398) and verbal fluency (ß=1.23, 95% CI −2.46 to 4.91, p=0.510). This pattern of findings was consistent in multivariable models.ConclusionsThe lack of group difference in cognition in our sample is likely due to a lack of clinical distinction between our groups. Future investigations should aim to use machine learning methods using longitudinal first episode samples to identify responder subtypes within schizophrenia, and how cognitive factors may interact within this.Trail registration numberREC: 15/LO/0038.

Impaired verbal memory function is related to anterior cingulate glutamate levels in schizophrenia: findings from the STRATA study

“…BACS composite t and z-scores, verbal memory, verbal fluency, working memory and attention and information processing speed were negatively correlated with PANSS negative subscale scores (Supplementary Table 2 ). As reported in our recent publication in the same cohort 55 , there was no difference in cognitive performance between groups prescribed antipsychotics with no or low versus high anticholinergic effects (see ref. 55 and Supplementary Materials ).…”

“…As reported in our recent publication in the same cohort 55 , there was no difference in cognitive performance between groups prescribed antipsychotics with no or low versus high anticholinergic effects (see ref. 55 and Supplementary Materials ).…”

“…A recent meta-analysis found that verbal memory impairments are more apparent in treatment-resistant compared to treatment-responsive schizophrenia 66 , and prospective investigation suggests this group difference is detectable from the first episode of psychosis 67 . However, cognitive performance did not differ between the good and poor antipsychotic response groups in our cohort 55 . We found no evidence that the relationship between glutamate and verbal memory differed between good and poor antipsychotic responders.…”

“…This study investigated the relationship between ACC glutamatergic metabolites and cognitive data in the STRATA-1 patient cohort, who were recruited according to their response to antipsychotic treatment. Within this cohort we previously reported higher glutamate levels in the ACC of antipsychotic non-responders compared to responders when controlling for age and sex 45 , but no group differences in cognition 55 . Based on the evidence above, our primary hypothesis was that there would be an inverted U-shaped association between ACC glutamate and cognition across the whole sample.…”

“…Both raw data entry and the BACS-t composite score calculation were checked for accuracy. We did not exclude this participant from analyses because, relative to the overall STRATA-1 cognition cohort, the BACS-t score fell within the range of the sample 55 . 1 H-MRS spectra were visually inspected, and the scan passed all our standard quality control procedures 45 .…”