Heterogeneity of serotonergic response in treatment-refractory schizophrenia patients

Oral metachlorophenylpiperazine (m-CPP) as a direct-acting postsynaptic serotonergic agonist was used to study serotonergic dysfunction in treatment-refractory chronic schizophrenia based on the hypothesis that some patients may show central serotonergic hypersensitivity. Seventeen DSM-III-R chronic schizophrenic patients with a history of neuroleptic nonresponse underwent double-blind challenge with oral m-CPP (0.25 mg/kg body weight) and placebo after medication washout. m-CPP significantly elevated both prolactin and cortisol levels as compared to placebo. There was a significant relationship between change in cortisol level and change in psychopathology under m-CPP; a blunted cortisol response was associated with a decrease in total psychopathology, while an increase in cortisol response related to an increase in psychopathology. Similarly, decrease in severity of the activation factor and the hostility factor was associated with a smaller cortisol response in the m-CPP condition. These results point to heterogeneity in central serotonergic sensitivity within the context of different subpopulations of serotonergic receptors.