Oxytocin and vasopressin 1a receptor alterations in the superior temporal sulcus and hypothalamus in schizophrenia

Schizophrenia is a severe psychiatric condition marked by social impairments. Given that social cognitive functioning strongly predicts life outcomes in schizophrenia, understanding its neurobiological basis is crucial. This study used receptor autoradiography to measure vasopressin 1a (AVPR1a) and oxytocin receptor (OXTR) densities in postmortem brain tissue from individuals with schizophrenia (<i>N</i> = 23) and matched controls (<i>N</i> = 18). We focused on the superior temporal sulcus, a region involved in social perception and often impaired in schizophrenia. AVPR1a binding densities exceeded those of OXTR. Notably, AVPR1a densities increased with age in females with schizophrenia, which may explain age-related changes in positive symptom severity (e.g. paranoia) in this group. Additionally, schizophrenia was associated with increased OXTR and a trend toward higher AVPR1a densities in the hypothalamus, a region central to oxytocin and vasopressin synthesis and stress response regulation. These findings suggest compensatory upregulation of nonapeptide receptor systems due to potentially reduced oxytocin and vasopressin release. Overall, our results highlight age- and sex-dependent alterations in receptor binding, providing insights into the neurobiology of social dysfunction in schizophrenia.