Eduardo S. Ghisolfi

Clozapine, but not typical antipsychotics, correct P50 suppression deficit in patients with schizophrenia.

OBJECTIVE To find out if there is a difference in P50 suppression between patients using typical antipsychotic drugs and those using clozapine, as well as to confirm the findings of abnormal P50 suppression in patients with schizophrenia, when compared to healthy volunteers. METHODS Fifty patients with schizophrenia and 25 healthy volunteers were divided into 3 groups: group 1 - patients using typical antipsychotics; group 2 - patients using clozapine; group 3 - controls. Before the examination, all patients were interviewed by a psychiatrist using the Brief Psychiatry Rating Scale (BPRS). RESULTS The average S2/S1 ratio was 0.82+/-0.45 in group 1, 0.57+/-0.41 in group 2, and 0.44+/-0.27 in group 3 (P=0.003). Statistical analysis showed a significant difference when the results of group 1 were compared to those of groups 2 (P=0.045) and 3 (P=0.001). There was no significant difference between groups 2 and 3 (P=0.182). There was a significant difference in the S1-S2 difference only between groups 1 and 3 (P=0.007), but a non-significant trend towards a similar difference was found between groups 1 and 2 (P=0.067). There was no correlation between the BPRS values and any P50 parameter. CONCLUSIONS The suppression of P50 among patients using clozapine was significantly greater than that obtained in patients using typical antipsychotics. SIGNIFICANCE This study confirms, in a more evident way, the improvement of the suppression of P50 potential in schizophrenics using clozapine. Additionally, it discusses the physiopathological mechanism involved.

Mate (chimarrão) é consumido em alta temperatura por população sob risco para o carcinoma epidermóide de esôfago

ABSTRACT – “Mate”, a popular hot infusion of a herb ( Ilex paraguayensis) drunk in large volumes, is a known risk factor for squamous cellcarcinoma of the esophagus and there is a suspicion that high temperature of boiled water used for the infusion may contribute for carcinogenesis. Methods - We measured the temperature of “mate” infusion drank by a sample of the population at risk for this carcinoma in Taquara, so uthernBrazil. We interviewed inhabitants for drinking habits and the temperature of the infusion was measured with high precision thermometers.Temperature of the infusion was asked to consumers and their estimate compared to our measurements. We considered 60 o C or higher as “hot”. Results - In 36 residencies, 107 individuals were drinking “mate”. Most individuals drunk it daily (97,2%), and the medium daily volume was1,265 ml (SD ± 1,132 mL) ranging from 250 to 6,000 mL. The measured temperature was 60 o C or higher in 72% of residencies with mediumof 63.4 o C (51-78 o

The Adenosine Antagonist Theophylline Impairs P50 Auditory Sensory Gating in Normal Subjects

In the P50 suppression paradigm, when two auditory stimuli are presented 500 ms apart, the amplitude of the second response (S2), compared with the first (S1), is markedly attenuated in healthy subjects. This is an index of sensory gating. Most schizophrenic patients fail to inhibit the P50 response to the second stimulus, which is assumed to reflect an inhibitory deficit. Adenosine is a neuromodulator with mostly inhibitory activity which is released by physiological stimuli. Since this inhibitory pattern resembles the phenomenon of sensory gating, the contribution of adenosine to P50 suppression was investigated in normal volunteers after treatment with the adenosine antagonist theophylline or placebo. P50 recordings were conducted in thirteen healthy subjects at baseline and 5, 30, 60, and 90 min after oral administration of theophylline (0.66 mg/kg, maximum dose of 500 mg) or placebo in a cross-over design. Baseline results from 17 drug-treated schizophrenic patients were included for comparison. Compared with placebo, theophylline treatment significantly increased P50 ratio (S2/S1) from 0.28 ± 0.03 to 0.82 ± 0.11 at 30 min and 0.61 ± 0.07 at 60 min (mean ± SEM), which were not significantly different from the schizophrenia group (0.74 ± 0.05). The increased P50 ratio by theophylline was due to a combined decrease in S1 and increase in S2 amplitude. The impairment of P50 suppression by theophylline in normal subjects suggests a modulatory role of adenosine in sensory gating, which may be related to P50 suppression deficit in schizophrenia and is in agreement with a hypoadenosinergic model of schizophrenia.

Caffeine modulates P50 auditory sensory gating in healthy subjects

The P50 suppression paradigm is an index of sensory gating assumed to reflect an inhibitory process. Adenosine is a neuromodulator with mostly inhibitory activity that is released by physiological stimuli and can be blocked by non-selective adenosine receptor antagonists such as theophylline and caffeine. A previous study showed that a single dose of theophylline decreased P50 suppression in healthy volunteers. Here we investigated the effect of caffeine (0, 100, 200 and 400 mg p.o.) on P50 sensory gating in 24 healthy volunteers (15 habitual caffeine high-users and 9 low-users). The 200 and 400 mg doses reduced P50 gating, whereas 100 mg produced a non-significant effect. The effect of caffeine was independent of gender and habitual caffeine intake. High caffeine users also showed baseline differences, with lower S(2) amplitudes compared to low-users. These results reinforce the participation of adenosine in the modulation of P50 sensory gating and suggest that caffeine ingestion should be controlled for in the P50 sensory gating paradigm.

Neurodevelopmental risk factors in schizophrenia

The authors review environmental and neurodevelopmental risk factors for schizophrenic disorders, with emphasis on minor physical anomalies, particularly craniofacial anomalies and dermatoglyphic variations. The high prevalence of these anomalies among schizophrenic subjects supports the neurodevelopmental theory of the etiology of schizophrenia, since they suggest either genetically or epigenetically controlled faulty embryonic development of structures of ectodermal origin like brain and skin. This may disturb neurodevelopment that in turn may cause these subjects to be at increased risk for the development of schizophrenia and related disorders. The precise confirmation of this theory, at least in some cases, will provide further understanding of these illnesses, allowing easy and inexpensive identification of subjects at risk and providing guidelines for the development of new pharmacological interventions for early treatment and even for primary prevention of the illness.