Profiling cognitive impairment in treatment-resistant schizophrenia patients

• Treatment resistance is associated with cognitive impairments across several cognitive domains in patients with schizophrenia.
• Antipsychotics with high anticholinergic activity negatively affect cognitive performance in patients with schizophrenia.
• Schizophrenia patients with treatment resistance in comparison to patients without treatment resistance perform worse on cognitive tests measuring processing speed, verbal fluency, cognitive flexibility and executive functions after controlling for confounding factors.

The aim of this study was to compare cognitive performance between schizophrenia patients with and without treatment resistance (TRS and non-TRS patients) taking into account psychopathological symptoms and antipsychotic treatment. The following cognitive tests were administered to 53 TRS patients and 32 non-TRS subjects: Rey Auditory Verbal Learning Test (RAVLT), Trail Making Tests (TMT-A and TMT-B), verbal fluency tests (FAS test and Supermarket), as well as selected Wechsler Adults Intelligence Scale (WAIS-R-PI) subtests: Digit Symbol Coding Test, Digit Span Forward and Backward and Similarities. TRS patients performed significantly worse in comparison with non-TRS patients on the measures of processing speed (TMT-A, Stroop test, FAS test, Supermarket test, Digit Symbol Coding test), verbal fluency (FAS test, Supermarket test), cognitive flexibility and executive functions (Stroop test) after controlling for age, illness duration, clinical symptoms severity, the number of years of completed education and antipsychotics’ dose. Cognitive performance was associated with negative and general symptomatology. Anticholinergic activity of antipsychotics had debilitating effect on cognitive functioning in non-TRS patients (FAS test) and in TRS patients (TMT-B test, Stroop test, RAVLT subtests, Digit Coding test and Similarities test), while low anticholinergic activity of antipsychotics was associated with better cognitive performance in non-TRS patients (Backward Digit Span test) and in TRS patients (Similarities test). Results of this study indicate that cognitive deficits are more robust in TRS patients than in non-TRS subjects, and are associated with clinical symptoms as well as the treatment with antipsychotics that exert high anticholinergic activity.