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

Abstract

AbstractSchizophrenia is a chronic, severe psychiatric condition characterized in part by social impairments. As social cognitive functioning is a major predictor of successful life outcomes in schizophrenia, there is a critical need to determine the neurobiological basis of social impairments in schizophrenia. The current study used receptor autoradiography to examine vasopressin 1a (AVPR1a) and oxytocin receptor (OXTR) densities in the postmortem brain tissue of individuals who had schizophrenia (N=23) relative to unaffected matched controls (N=18). We analyzed the superior temporal sulcus, a brain region that is highly implicated in social perception and shows aberrant functioning in schizophrenia. GreaterAVPR1a binding densities were observed relative to OXTR. Increases in AVPR1a densities with advanced age in females who had schizophrenia were also observed. This finding in the superior temporal sulcus may explain a shift in positive symptom severity(paranoia/suspiciousness) that has been observed with advanced age in women with schizophrenia. In addition, increased OXTR and a trend toward increased AVPR1a densities were observed in the hypothalamus in schizophrenia. The hypothalamus synthesizes oxytocin and vasopressin in the brain and is the initiator of the hypothalamic-pituitary-adrenal axis, which facilitates the fight or flight stress response. These receptor systems may be upregulated to compensate for possibly low exogenous oxytocin and vasopressin release from the hypothalamus in schizophrenia. Our findings show age- and sex-dependent effects on nonapeptide receptor binding that shed light onto the neurobiology of the social brain in the progression of schizophrenia.