Abstract

Approximately one third of psychosis patients fail to respond to conventional antipsychotic medication, which exerts its effect via striatal dopamine receptor antagonism. The present study aimed to investigate impaired cognitive control as a potential contributor to persistent positive symptoms in treatment resistant (TR) patients. 52 medicated First Episode Psychosis (FEP) patients (17 TR and 35 non-TR (NTR)) took part in a longitudinal study in which they performed a series of cognitive tasks and a clinical assessment at two timepoints, 12 months apart. Cognitive performance at baseline was compared to that of 39 healthy controls (HC). Across both timepoints, TR patients were significantly more impaired than NTR patients in a task of cognitive control, while performance on tasks of phonological and semantic fluency, working memory and general intelligence did not differ between patient groups. No significant associations were found between cognitive performance and psychotic symptomatology, and no significant performance changes were observed from the first to second timepoint in any of the cognitive tasks within patient groups. The results suggest that compared with NTR patients, TR patients have an exacerbated deficit specific to cognitive control, which is established early in psychotic illness and stabilises in the years following a first episode.

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