The objective of this study was to test our preliminary in vivo evaluations of central cholinergic abnormalities in schizophrenia patients. Short latency afferent inhibition (SAI) is based on coupling peripheral nerve stimulation with motor cortex Transcranial Magnetic Stimulation (TMS), which has been shown to be a putative marker of central cholinergic activity. Methods: We evaluated SAI in 5 patients with schizophrenia and 5 healthy subjects. Results: The level of SAI was significantly lower in the patients with schizophrenia than in the controls (p=0.008). Conclusion: Our findings suggest involvement of central cholinergic neurotransmission in schizophrenia, which indicates a possible approach for treatment of cognitive dysfunction related to the disease.

We investigated the possible association between genetic polymorphisms in the dopamine receptor and serotonin transporter genes and the responses of schizophrenic patients treated with either risperidone or perospirone. The subjects comprised 27 patients with schizophrenia who were clinically evaluated both before and after treatment. The genotyping of the polymorphisms of the dopamine D2 receptor gene (DRD2) (rs1801028 and rs6277), the dopamine D4 receptor gene (DRD4) (120-bp tandem repeats and rs1800955), and serotonin transporter gene (5HTT)(variable number of tandem repeats; VNTR) were performed using the real-time polymerase chain reaction and sequencing. In DRD2 and 5HTT-VNTR, there were no significant correlations between clinical response and polymorphism in the case of risperidone, and for perospirone treatment it was impossible to analyze the clinical evaluation due to the absence of genotype information. On the other hand, in DRD4 there were significant correlations in the two-factor interaction effect on the Positive and Negative Syndrome Scale (PANSS) between the two drugs [120-bp tandem repeat, p=0.003; rs1800955, p=0.043]. Although the small sample represents a serious limitation, these results suggest that variants in DRD4 are a predictor of whether treatment will be more effective with risperidone or with perospirone in individual patients.
Genotype ; Hand ; Humans ; Isoindoles ; Polymorphism, Genetic ; Real-Time Polymerase Chain Reaction ; Receptors, Dopamine ; Receptors, Dopamine D2 ; Receptors, Dopamine D4 ; Risperidone ; Schizophrenia ; Serotonin Plasma Membrane Transport Proteins ; Tandem Repeat Sequences ; Thiazoles