INDEPENDENT GENETIC EVIDENCE LINKS STRIATAL-ENRICHED PROTEIN TYROSINE PHOSPHATASE (STEP) TO HUMAN ATTENTION AND SCHIZOPHRENIA-RELATED TRAITS

Background Genetic association and protein expression findings in humans and observations in animal models, have implicated the STriatal-Enriched protein tyrosine Phosphatase (STEP) in cognitive functioning and schizophrenia. Methods Here, we aimed to confirm the association between common genetic polymorphisms within PTPN5 encoding STEP, and sustained attention performance assessed with the Continuous Performance Test-Identical Pairs (CPT-IP) among healthy young males (n=1814) and individuals diagnosed with Schizophrenia (SZ; n=341) or Bipolar Disorder (BP; n=239). Moreover, self-rated schizotypal traits and subclinical Psychotic Experiences (PEs) were examined in healthy males, as well as symptom dimensions in an extended SZ data set (n=647). Results We observed that rs10766504, previously associated with increased CPT-IP omission errors among healthy females, predicted greater CPT-IP target detectability in both healthy males and SZ/BP patients (p Discussion These findings underscore PTPN5 as a highly promising candidate gene for sustained attention that merits further genetic and functional investigation. This study also suggests that PTPN5 exerts pleiotropic effects on attention performance and behavioral expressions, which have been linked to altered striatum activity.