Serotonin 5-HT2 receptors in schizophrenia: A PET study using [F-18]setoperone in neuroleptic-naive patients and normal subjects

Objective: Several postmortem studies have reported a decreased density of serotonin 5-HT2 receptors in the prefrontal cortex in schizophrenia. The pu rpose of this study was to investigate this in patients with schizophrenia by means of [F-18]setoperone and positron emission tomography (PET) imaging . Method: Thirteen neuroleptic-free patients with schizophrenia, 10 of whom were also neuroleptic-naive, were compared with a group of 26 normal subje cts in the same age range. The density of 5-HT2 receptors was assessed with the use of [F-18]setoperone and PET in standardized cortical regions of in terest. Results: Increasing age was associated with similar declines in 5-H T2 receptors in all cortical regions in the patient group and in the normal comparison group. After control for the effect of age, there was no statis tically significant difference between the patients and the comparison subj ects in 5-HT2 receptor density in any of the cortical regions. Conclusions: This study failed to find the decrease in 5-HT2 receptors reported in post mortem studies of schizophrenia. The study had the power to detect a decrea se of 25% or more in 5-HT2 receptors, which was anticipated on the basis of the previous postmortem studies. Thus, a primary serotonergic abnormality in schizophrenia, if one exists, is either small or unlikely to be at the l evel of the 5-HT2 receptors. This finding does not rule out a therapeutic r ole for 5-HT2 antagonists in schizophrenia, but it does suggest that the th erapeutic contribution is likely to be an indirect one.