Overexpression of serotonin receptor and transporter mRNA in blood leukocytes of antipsychotic-free and antipsychotic-naïve schizophrenic patients: Gender differences

BackgroundAbnormal serotonin (5-HT) activity has been implicated in schizophrenia. However, the role of 5-HT receptors and transporter (5-HTT) in male and female schizophrenia remains largely unknown. Recent studies suggest that 5-HT system expressed in the peripheral leukocyte could be a marker of the illness.Methods46 acute schizophrenic patients (male=35, female=11) that were antipsychotic-naïve or antipsychotic-free for at least three months (average=27.3 months) and 44 age- and sex-matched healthy subjects (male=24, female=20) were included for blood leukocytes expression of 5-HT1A, 5-HT2A and 5-HT7 receptor and 5-HTT mRNA, using real-time PCR technique.ResultsANOVA analysis showed a significant increase of 5HT2A mRNA and 5-HTT mRNA (each > 2-fold, P < 0.01) and a trend increase of 5HT1A mRNA (P < 0.15) and 5-HT7 mRNA (P < 0.09) level in blood leukocytes of pooled schizophrenic patients than in the healthy subjects. The elevation was mainly found in the male patients. Within-sex analysis showed that the male antipsychotic-free schizophrenic patients exhibited greater 5-HT1A and 5-HT7 mRNA expression (P<0.05, each ) whereas female antipsychotic-free patients showed decreased 5-HT1A mRNA expression (P<0.05) when compared with the male and female healthy subjects, respectively. The correlations between 5-HT mRNA and clinical symptoms (PANSS scales) were calculated.ConclusionsThe present findings showed an abnormal expression of leukocyte 5-HT system in antipsychotic-free and antipsychotic-naïve schizophrenia especially in the male patients. Because of the greater accumulative dose of antipsychotics in the relatively smaller number of the female patients of the study, further study is needed to confirm the present findings. If replicated, blood serotonergic markers could add to the diagnosis and individualized pharmacotherapy of schizophrenic patients, especially the male patients.