Oxytocin system dysfunction in patients with treatment-resistant schizophrenia: Alterations of blood oxytocin levels and effect of a genetic variant of OXTR

Treatment-resistant schizophrenia (TRS) has a quite complex pathophysiology that includes not only severe positive symptoms but also other symptom domains. Much attention has been devoted to the overlapping psychological and biological profiles of schizophrenia and autistic spectrum disorder (ASD). We compared TRS patients (n = 30) with schizophrenia patients in remission (RemSZ, n = 28) and ASD patients (n = 28), focusing on general cognitive and social cognitive impairment and oxytocin system dysfunction. Our analyses revealed that there was no difference in oxytocin concentration among the three groups. The TRS patients’ oxytocin blood concentrations were positively correlated with their processing speed and theory-of-mind scores, whereas the RemSZ and ASD groups had no significant relation with any measures. Rs53576, a single nucleotide polymorphism on the oxytocin receptor gene, affected social cognition abilities in the schizophrenia group. Although the overall findings are preliminary, they indicate that oxytocin system dysfunction could be involved in the serious cognitive deficits in TRS patients. Further, these results suggest that patients with TRS might have early neurodevelopmental abnormalities based on their shared biological features with ASD patients. •・Oxytocin system abnormalities were implicated in the etiologies of psychiatric disorders such as autistic spectrum disorder (ASD) and schizophrenia. Although this system has been considered to be related to several symptom domains of these disorders, it is uncertain how and why oxytocin is involved in multiple psychopathologies.•・The present study measured the serum concentrations of oxytocin and sequenced the OXTR gene for the two schizophrenia group (treatment-resistant schizophrenia (TRS), n = 30; remission schizophrenia (RemSZ), n = 28) and the ASD group (n = 28).•・The blood concentration of oxytocin was positively correlated with process of speed in general cognitive measurements and theory-of-mind in social cognitive measurement in the TRS group. However, any relationship between oxytocin concentration and general/cognitive domains was not observed in the RemSZ and ASD group.•・G allele carriers of rs53576, an intronic SNP on the OXTR gene, in the schizophrenia group were worse in theory-of-mind score to non-G allele carriers.•・These findings suggest that oxytocin system dysfunction could affect profoundly treatment-refractory symptoms through mediating social cognitive process in pati