P50 sensory gating in panic disorder.

Previous studies with prepulse inhibition in panic disorder (PD) have suggested that the early stages of sensory information processing are abnormal in patients with PD. To further investigate sensory gating function in panic disorder we performed a case-control study in a sample of 28 patients with PD, compared to 28 normal subjects and 28 schizophrenic subjects evaluating auditory mid-latency evoked potential P50 in a double-click paradigm as a measure of sensory gating. PD subjects showed weaker sensory gating as evidenced by higher P50 ratios as compared to normal subjects (62.5% vs. 45.4%, p=0.03) and higher S2 (test) amplitude (3.5 microV vs. 2.1 microV, p=0.01). Schizophrenic subjects when compared to healthy controls showed higher P50 ratios as compared to normal subjects (79.2% vs. 45.4%, p<0.01) and higher S2 amplitude (3.3 microV vs. 2.1 microV, p=0.01), but were not statistically different from PD subjects (p>0.1). The present study corroborates recent findings of sensory gating dysfunction in PD. Further studies are still necessary to better understand the pathophysiology of this neurophysiological dysfunction and its nature as a trait or a state marker.

Involvement of adenosine in the neurobiology of schizophrenia and its therapeutic implications.

Based on the neuromodulatory and homeostatic actions of adenosine, adenosine dysfunction may contribute to the neurobiological and clinical features of schizophrenia. The present model of adenosine dysfunction in schizophrenia takes into consideration the dopamine and glutamate hypotheses, since adenosine exerts neuromodulatory roles on these systems, and proposes that adenosine plays a role in the inhibitory deficit found in schizophrenia. Given the role of adenosine activation of adenosine A1 receptor (A1R) in mediating neurotoxicity in early stages of brain development, pre- and peri-natal complications leading to excessive adenosine release could induce primary brain changes (i.e., first hit). These events would lead to an adenosine inhibitory deficit through a partial loss of A1R that may emerge as reduced control of dopamine activity and increased vulnerability to excitotoxic glutamate action in the mature brain (i.e., second hit). Adenosine dysfunction is reasonably compatible with symptoms, gray and white matter abnormalities, progressive brain loss, pre- and peri-natal risk factors, age of onset, response to current treatments, impaired sensory gating and increased smoking in schizophrenia. Pharmacological treatments enhancing adenosine activity could be effective for symptom control and for alleviating deterioration in the course of the illness. Accordingly, allopurinol, which may indirectly increase adenosine, has been effective and well tolerated in the treatment of schizophrenia. Since much of the evidence for the adenosine hypothesis is preliminary and theoretical, further investigation in the field is warranted.

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.

Geradores do P50: estudo com pacientes epilépticos, submetidos á amígdala-hipocampectomia / P50 generators: study with epileptic patients submitted on the amigadala-hippocampectomy

Estudar o envolvimento do hipocampo na gênese dopotencial evocado P50 e da supressão do mesmo em pacientes com epilepsia submetidos a tratamento cirúrgico. Foi realizado um estudo transversal com grupo de controle de comparação. Excluíram-se indivíduos com outra patologia neurológica ou psiquiátrica, hipoacusia auditiva, história familiar de transtornos psicóticos, uso de antipsicóticos atípicos ou de drogas ilícitas no último mês. Os indivíduos foram separados em dois grupos: grupo 1 (n=34) - amígdala-hipocampectomia; grupo 2 (n=40) - controles. Foi realizado, em todos os participantes, o potencial evocado auditivo de m,édia latência P50. Consideraram-se variáveis de comparação

A clinical trial of adjuvant allopurinol therapy for moderately refractory schizophrenia.

OBJECTIVE: To evaluate the xanthine oxidase inhibitor allopurinol as an adjuvant treatment for patients with moderately refractory schizophrenia, with the objective of increasing the endogenous pool of purines, including the neuro-modulator adenosine. METHOD: A double-blind, placebo-controlled, crossover clinical trial of add-on allopurinol (300 mg b.i.d.) for poorly responsive schizophrenia or schizoaffective disorder (DSM-IV criteria) was conducted. Thirty-five patients were enrolled, of whom 22 completed the 12 weeks of the study. Eighteen of these patients also completed a P50 evoked potential evaluation. RESULTS: Allopurinol was well tolerated and produced significant improvement in Positive and Negative Syndrome Scale (PANSS) total, positive, negative, and general scores, particularly for positive symptoms compared with baseline and with placebo phase. Nine patients improved more than 20% in PANSS total score during allopurinol treatment, whereas none responded in the placebo phase. Responders had a shorter duration of illness than nonresponders. P50 auditory sensory gating failed to improve with allopurinol treatment. CONCLUSIONS: Allopurinol was an effective and well-tolerated adjuvant treatment for poorly responsive schizophrenia, especially for refractory positive symptoms.

Impaired P50 sensory gating in Machado-Joseph disease.

OBJECTIVE: Machado-Joseph disease (MJD), an autosomal dominant spinocerebellar degeneration caused by an expanded CAG repeat on chromosome 14q32.1, is a disorder with wide range of neurological findings and brain regions involved. Studies evaluating neurophysiological parameters related to sensory gating in MJD are lacking. METHODS: This study intends to investigate P50 suppression, an auditory mid-latency evoked potential in a test-conditioning paradigm, considered as an index of sensory gating function. Twelve patients with MJD, 24 normal subjects and 12 schizophrenic patients were evaluated. RESULTS: MJD subjects had higher P50 ratios as compared to normal subjects (76.2 vs. 42.1%, P = 0.001), but similar to the group of schizophrenic patients. The difference from controls was due to greater test amplitudes (3.4 vs. 2.0 microV, P = 0.002), rather than to conditioning amplitudes. Latencies were higher for the MJD subjects than for controls (60.4 vs. 56.1 ms, P = 0.016). CONCLUSIONS: MJD may present sensory gating dysfunction. However, the pattern of this dysfunction seems to slightly differ from that classically found in schizophrenia, were both test and conditioning amplitudes seem to be implicated. SIGNIFICANCE: These results point out the P50 paradigm as a potential tool for further neurophysiological surveying in MJD.

Impaired P50 sensory gating in post-traumatic stress disorder secondary to urban violence.

Previous studies on sensory gating process in post-traumatic stress disorder (PTSD) have yielded conflicting results. To investigate sensory gating function in PTSD we performed a case-control study in a sample of 12 patients with PTSD related to urban violence, compared to 24 normal subjects and 12 schizophrenic subjects evaluating auditory mid-latency evoked potential P50 in a double-click paradigm as a measure of sensory gating. PTSD subjects showed poorer sensory gating as evidenced by higher P50 ratios as compared to normal subjects (85.6% vs. 44.4%, P=0.002). Test and conditioning amplitudes did not differ with statistical significance alone, suggesting a combined effect. Schizophrenic subjects had higher conditioning and marginally smaller test amplitudes when compared to healthy controls, but were not statistically different from PTSD subjects. The present study replicated previous findings of sensory gating dysfunction in PTSD. The pattern of this dysfunction resembles that found in schizophrenia, with both test and conditioning amplitudes possibly implicated. Further studies are still necessary to better understand the pathophysiology of this neurophysiological dysfunction and its nature as a trait or state marker. The P50 paradigm may also become an objective parameter to assess the effects of new treatments for PTSD.

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.

Neuropsychiatric evaluation in subjects chronically exposed to organophosphate pesticides.

Long-term exposure to low levels of organophosphate pesticides (OP) may produce neuropsychiatric symptoms. We performed clinical, neuropsychiatric, and laboratory evaluations of 37 workers involved in family agriculture of tobacco from southern Brazil who had been exposed to OP for 3 months, and in 25 of these workers, after 3 months without exposure to OP. Plasma acetylcholinesterase activity levels of all subjects were within the normal range (3.2 to 9.0 U/l) and were not different between on- and off-exposure periods (4.7 +/- 0.9 and 4.5 +/- 1.1 U/l, respectively). Clinically significant extrapyramidal symptoms were present in 12 of 25 subjects, which is unexpected in such a population. There was a significant reduction of extrapyramidal symptoms after 3 months without exposure to OP, but 10 subjects still had significant parkinsonism. Mini-mental and word span scores were within the expected range for this population and were not influenced by exposure to OP. Eighteen of the 37 subjects (48%) had current psychiatric diagnoses in the first interview (13 with generalized anxiety disorder and 8 with major depression). Among the 25 subjects who completed both evaluations, the total number of current psychiatric diagnoses, after 3 months without using OP, dropped from 24 to 13 and the number of affected individuals with any psychiatric diagnosis dropped from 11 to 7. In conclusion, this study reinforces the need for parameters other than acetylcholinesterase activity to monitor for chronic consequences of chronic low-dose OP exposure, and it suggests that subjects have not only transient motor and psychiatric consequences while exposed, but may also develop enduring extrapyramidal symptoms.

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.

Transexualismo: uma revisão / Transexualism: a review

A procura de atendimento médico-cirúrgico por parte de pacientes exibindo transexualismo (CID-10) ou transtorno de identidade de gênero (DSM-IV) tem crescido de forma importante no Hospital de Clínicas de Porto Alegre. Com o objetivo de melhor caracterizar tal entidade nosológica, efetuou-se um estudo de revisão bibliográfica, baseado em revisão não-sistemática. Tais pacientes apresentam uma angústia persistente em relação ao seu sexo anatômico, associada a um forte desejo de mudar para o outro sexo. Apesar de ser uma entidade rara, o impacto da vida desses pacientes é intenso. De etiologia predominantemente biológica, a terapêutica preconizada consiste nos procedimentos de redesignação sexual (hormonoterapia, cirurgia de transgenitalização, etc). A abordagem adequada deve ser multidisciplinar e simultânea, tendo o acompanhamento psiquiátrico um papel fundamental