Decreased Dopamine D2 Receptor Binding in the Anterior Cingulate Cortex in Schizophrenia

Abstract

Background:The clinical efficacy of dopamine D 2 receptor antagonism on the psychotic symptoms of schizophrenia has been widely demonstrated. However, most in vivo imaging studies have not been able to detect significant changes in striatal D 2 receptors in schizophrenia. On the other hand, a number of studies have reported abnormalities in the cerebral cortex of schizophrenia. The aim of this study was to examine the extrastriatal D 2 receptors of patients with schizophrenia.Methods: Eleven drug-naive male patients with schizophrenia were examined with positron emission tomography using carbon 11-labeled FLB 457. Symptoms were assessed using the Brief Psychiatric Rating Scale. Eighteen healthy controls were used for comparison. Regionof-interest analysis was performed using the reference tissue method, and binding potential (BP) was used for the index of dopamine D 2 receptor binding.Results: The BP value was significantly lower, by about 12.5%, in the anterior cingulate cortex in drug-naive patients with schizophrenia than in healthy controls. A significant negative correlation was observed between BP in the anterior cingulate cortex and the positive symptom score on Brief Psychiatric Rating Scale. Conclusions:The lower BP values indicate fewer D 2 receptors in the anterior cingulate cortex in patients with schizophrenia. Alterations in D 2 receptor function in the extrastriatal region may underlie the positive symptoms of schizophrenia.

Effect of Prenatal Cocaine Exposure on D2 Receptors and DAT in Rhesus Macaques

“…analysis of the same anterior cingulate cortex ROIs provided plausible binding potential values which were in agreement with previous research (Suhara et al 2002;Hagelberg et al 2004;Talvik et al 2003;Kaasinen et al 2000). Based on the consistent response of the data to the MRTM2 analysis, but not to the Logan model analysis, it was conjectured that high levels of noise were present in the anterior cingulate cortex.…”

The Striatal and Extrastriatal D2/D3 Receptor-Binding Profile of Clozapine in Patients with Schizophrenia

“…If there is indeed a reduced temporal cortical D 2 receptor density in schizophrenia, this would produce spuriously high levels of dopamine D 2 /D 3 receptor occupancy in patients with schizophrenia when using normal volunteers as control subjects. However, both Suhara et al (2002b) and Talvik et al (2003), using PET with [ 11 C]FLB-457, failed to find significant reductions in temporal cortical D 2 receptor availability in larger samples of 11 and nine patients, respectively. Furthermore, with the exception of the thalamus, we demonstrated a higher extrastriatal than striatal occupancy not only in the temporal cortex but also throughout the brain.…”

Chronic NMDA Antagonism Impairs Working Memory, Decreases Extracellular Dopamine, and Increases D1 Receptor Binding in Prefrontal Cortex of Conscious Monkeys

“…The role of the antagonistic effects of NMDA receptors has been of interest because of hypofunction of glutamatergic neurotransmission in the PFC (Carlsson et al, 1997), and its relationship to dopaminergic dysfunction (Robbins, 1990;Grace, 1991;Deutch, 1992), which has been hypothesized in schizophrenic patients. Recent PET studies have supported dysfunction of the extrastriatal dopaminergic system in schizophrenic patients (Okubo et al, 1997;Abi-Dargham et al, 2002;Suhara et al, 2002). The Okubo et al (1997) The PFC dopaminergic system is also vulnerable to stress.…”

“…[ 11 C]NNC112 (Halldin et al, 1998) and [ 11 C]FLB457 (Halldin et al, 1995) have been developed to assess the extrastriatal neocortical receptor D 1 (D 1 R) and D 2 (D 2 R), respectively. Recent PET studies have suggested the dysfunction of the extrastriatal dopaminergic system in schizophrenic patients (Okubo et al, 1997;Abi-Dargham et al, 2002;Suhara et al, 2002).…”