Cortical and Subcortical 5-HT2A Receptor Binding in Neuroleptic-Naive First-Episode Schizophrenic Patients

Abstract

The serotonin 5-HT 2A receptor is suspected to be involved in a number of psychiatric disorders, including schizophrenia. In particular, atypical antipsychotics have antagonistic effects on the 5-HT 2A receptors, supporting a specific role of the 5-HT 2A receptor in the pathophysiology of this disease. The aim of this study is to investigate cortical and subcortical 5-HT 2A binding in neuroleptic-naive schizophrenic patients. Fifteen neuroleptic-naive patients diagnosed with schizophrenia (age 27.5 ± 4.5 years), 11 men and 4 women, and 15 healthy control subjects matched for age (28.5 ± 5.7 years) and gender underwent a 40 min positron emission tomography (PET) study using the 5-HT 2A antagonist, [18 F]altanserin, as a radioligand. PET images were co-registered to 3 T magnetic resonance images (MRIs) for each individual subject, and ROIs were applied automatically onto the individual MRIs and PET images. The cerebellum was used as a reference region. The binding potential of specific tracer binding (BP p ) was used as the outcome measure. No significant difference was seen in cortical receptor distribution between patients and controls. An increase in 5-HT 2A receptor binding in the caudate nucleus was detected in the group of schizophrenic patients (0.7 ± 0.1) when compared to the healthy controls (0.5 ± 0.3) (p ¼ 0.02). Our results confirm other in vivo findings of no difference in cortical 5-HT 2A receptor binding between first-episode antipsychotic-naive schizophrenic patients and age-and gender-matched healthy control subjects. However, a preliminary finding of increased 5-HT 2A binding in the caudate nucleus requires further investigation to explore the relation of subcortical and cortical 5-HT 2A receptor binding.

Serotonin and Schizophrenia

“…However, both tracers suffer from a relatively low affinity for 5-HT 2A receptors and, thus, they have an insufficient signal-to-noise ratio in subcortical areas (Erritzoe et al, 2008). In contrast, one study using (Erritzoe et al, 2008).…”

“…However, both tracers suffer from a relatively low affinity for 5-HT 2A receptors and, thus, they have an insufficient signal-to-noise ratio in subcortical areas (Erritzoe et al, 2008). In contrast, one study using (Erritzoe et al, 2008). Two further studies investigated 5-HT 2A receptor density with [ 18 F]altanserin PET in subjects supposed to be in a prodromal state of schizophrenia and reported both decreased binding of the radio tracer in the PFC (Hurlemann et al, 2005(Hurlemann et al, , 2008.…”

Decreased Frontal Serotonin2A Receptor Binding in Antipsychotic-Naive Patients With First-Episode Schizophrenia

“…[31][32][33][34][35] The majority of these studies, including our own, 54 were unable to identify differences in cortical serotonin 2A binding between schizophrenic patients and healthy control subjects. In our previous study 38 we found increased serotonin 2A receptor binding in the caudate nucleus.…”

“…Fifteen of the patients were identical to the patients included in our previous preliminary study. 35 A decrease in serotonin 2A binding in the frontal cortex in these patients compared with matched healthy control subjects was expected a priori. We also expected to confirm our preliminary finding of serotonin 2A receptor upregulation in the caudate nucleus.…”

“…34 These studies are limited by small sample sizes and by their use of the radioligands setoperone labeled with fluorine 18 and N-methylspiperone labeled with carbon 11, which have a relatively low serotonin 2A receptor selectivity. 35 The radioligand altanserin labeled with fluorine 18 is highly selective for the serotonin 2A receptor and allows measurements of serotonin 2A receptor availability in both cortical and subcortical regions. 31,36,37 In a previous preliminary study, our group reported the use of this radioligand in 15 antipsychotic-naive schizophrenic patients.…”