Multireceptor fingerprinting of schizophrenia Tetsuya Suhara Chiba

The symptoms of schizophrenia have been discussed with a functional impairment of various brain circuits and altered dopaminergic transmission. Dopamine receptors are classified into five subtypes, and selective ligands have been developed for D1 and D2 subtypes. An increasing body of evidence favors a crucial role of extrastriatal regions in the pathophysiology of positive symptoms, and the extrastriatal D2 receptor is expected to be the common site of action of antipsychotics. Using [¹¹C]FLB 457, we found reduced D2 receptor binding in the anterior cingulate cortex of patients with schizophrenia, and a significant negative correlation was observed between D2 receptor binding and the positive symptom score on BPRS. Subregions of interest were defined on the thalamus using individual magnetic resonance images (MRI). D2 receptor binding was also lower in the central medial and posterior subregions of the thalamus in patients with schizophrenia. Alterations in D2 receptor function in the extrastriatal region may underlie the positive symptoms of schizophrenia. On the other hand D1 receptor binding was found to be lower in the prefrontal cortex and a significant negative correlation was observed between D1 receptor binding and the negative symptom score on BPRS. Abnormality of D1 receptor function would be at the bottom of the negative symptoms and cognitive impairment of schizophrenia. Several lines of evidence suggested that serotonin function may also be involved in the pathophysiology of schizophrenia. 5-HT_1A receptor binding in the patients with schizophrenia measured by [¹¹C]WAY-100635 was lower in the amygdala compared to the normal controls and a significant negative correlation was observed between 5-HT_1A receptor binding in the amygdala and the negative and depression/anxiety symptom scores. However, no significant difference was observed in 5-HT_2A receptor binding between patients with schizophrenia and normal controls.