[P300 in mild cognitive impairment and in dementia]. / P300 enyhe kognitív zavarban és demenciában.

OBJECTIVES: The late component of the event-related potential (ERP), P300 is a marker for cognitive brain functions. The objective of this study was to examine P300 parameters in dementia and in mild cognitive impairment (MCI), to examine whether there is a correlation between the changes in P300 parameters and the type and severity of dementia, and to determine P300 abnormalities in MCI in relation to the presence/absence of CT/MRI abnormalities. METHOD: Auditory event-related potentials, P300 were recorded in 28 MCI patients (14 of them with normal CT/MRI findings and 10 subjects with mild ventricular enlargement). In another group of patients, 31 demented patients were examined, of whom 17 patients were diagnosed with Alzheimer's dementia (AD), and 14 patients with vascular dementia (VD). Forty healthy volunteers served as the control group. RESULTS: Mean P300 latency was significantly increased for both demented patient-groups. We found that prolongation of P300 latency was correlated with the severity of dementia. Mean P300 amplitude was significantly decreased in both groups of demented patients. In MCI, the mean latency of P300 was significantly longer among patients with mild cerebral atrophy compared to control volunteers and no significant changes were found for MCI patients with normal CT/MRI findings. Mean P300 amplitude was decreased only in demented patients. CONCLUSIONS: The prolongation of P300 latency was significant among patients with both vascular and Alzheimer's dementia, and also among MCI patients with mild cerebral atrophy. The severity of dementia is positively correlated with P300 latency; however, this prolongation is independent of the type of dementia. The structural brain changes in MCI are related to P300 latency prolongation and thus may indicate an increased risk for developing dementia in MCI patients.

Automated Neuropsychological Test Battery (CANTAB) in mild cognitive impairment and in Alzheimer's disease.

Neuropsychological deficits, such as poor episodic memory, are consistent features of mild cognitive impairment and also that of early stage of dementia. The aim of the present study was to detect cognitive dysfunction among patients with Alzheimer's disease or with mild cognitive impairment (MCI), which refers to a transitional state between the cognition of normal aeging and mild dementia regarded as a high-risk condition for the development of clinically probable Alzheimer's disease (AD). Computerized tests of memory, attention and executive functions were studied in groups of AD subjects (n=15) and MCI subjects (n=25). On all measures, the performance of the AD group was significantly weaker compared to healthy individuals or to the MCI group. The performance of both the AD and MCI patients in the Paired Associate Learning test was significantly impaired, which may suggest that MCI patients are already in the early stages of the disease.

Brain blood flow changes measured by positron emission tomography during an auditory cognitive task in healthy volunteers and in schizophrenic patients.

OBJECTIVE: Cognitive deficit is an essential feature of schizophrenia. One of the generally used simple cognitive tasks to characterize specific cognitive dysfunctions is the auditory "oddball" paradigm. During this task, two different tones are presented with different repetition frequencies and the subject is asked to pay attention and to respond to the less frequent tone. The aim of the present study was to apply positron emission tomography (PET) to measure the regional brain blood flow changes induced by an auditory oddball task in healthy volunteers and in stable schizophrenic patients in order to detect activation differences between the two groups. METHOD: Eight healthy volunteers and 11 schizophrenic patients were studied. The subjects carried out a specific auditory oddball task, while cerebral activation measured via the regional distribution of [15O]-butanol activity changes in the PET camera was recorded. RESULTS AND DISCUSSION: Task-related activation differed significantly across the patients and controls. The healthy volunteers displayed significant activation in the anterior cingulate area (Brodman Area - BA32), while in the schizophrenic patients the area was wider, including the mediofrontal regions (BA32 and BA10). The distance between the locations of maximal activation of the two populations were 33 mm and the cluster size was about twice as large in the patient group. CONCLUSIONS: The present results demonstrate that the perfusion changes induced in the schizophrenic patients by this cognitive task extends over a larger part of the mediofrontal cortex than in the healthy volunteers. The different pattern of activation observed during the auditory oddball task in the schizophrenic patients suggests that a larger cortical area - and consequently a larger variety of neuronal networks--is involved in the cognitive processes in these patients. The dispersion of stimulus processing during a cognitive task requiring sustained attention and stimulus discrimination may play an important role in the pathomechanism of the disorder.

[Switching patients with schizophrenia to ziprasidone from conventional or other atypical antipsychotics]. / Váltás ziprasidonra hagyományos vagy más atípusos antipszichotikumokról szkizofréniában szenvedö betegekben.

OBJECTIVES: The aim of the study was to assess the efficacy, tolerability and safety of ziprasidone in patients with schizophrenia who were already treated with conventional or other atypical antipsychotics that had to be switched due the lack of efficacy or bad tolerance. METHODS: The study was a 12-week, open label, multicenter, non comparative trial on oral ziprasidone. 106 patients with DSM-IV schizophrenia were switched to ziprasidone from their previous antipsychotic without a washout phase. The study required fixed dosing with ziprasidone. For the first week the patient received 80 mg of study drug daily, followed for 3 weeks 120 mg/day. Subsequently for 8 weeks either 80 mg, or 120 mg, or 160 mg total daily dose could be given at the discretion of the investigator. Baseline and outcome assessment included Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Severity of Illness Subscale (CGI-S) and Global Improvement Subscale (CGI-I), Calgary Depression Scale (CAD), Hamilton Depression Scale (HAMD), Drug Attitude Inventory (DAI), Simpson Angus Extrapyramidal Symptoms Rating Scale (SAS) and Barnes Akathisia Rating Scale (BARS). Changes in overall body weight were also evaluated. RESULTS: After 12 weeks on ziprasidone therapy, significant improvements were observed on all major symptoms measures and subscales. 34 (51,5%) patients (ITT) were rated much or very much improved on CGI-I at week 12. The mean SAS score significantly reduced during the ziprasidone treatment period (p<0.001). In the DAI ziprasidone treatment was also favorable rated. During treatment with ziprasidone for 12 weeks the body weight of the patients was significantly reduced (mean: 1,2 kg, SD=3,79, p=0.002). 58 adverse events occurred in 41 subjects (38.7%), of whom 7 patients (6.6%) encountered 9 severe adverse events. The adverse events were mainly mild and moderate. 15 patients (14.2%) were discontinued from the study due to adverse events. The reason for discontinuation in 4 cases was mainly insufficient clinical response. CONCLUSION: Switching patients from their previous antipsychotic to ziprasidone without a washout phase was generally well tolerated and was associated with symptoms improvements 12 weeks later. At least 50% of patients who needed to be switched because of unsatisfactory efficacy or poor tolerance were significantly improved on ziprasidone therapy. The favorable safety profile of ziprasidone treatment was consistent with that seen in other clinical trials. KEYWORDS: switching, ziprasidone, schizophrenia.

[Cognitive functions in prepsychotic and negative-symptom schizophrenic patients]. / Kognitív funkciók prepszichotikus és negatív tünetes szkizofrén betegekben.

BACKGROUND: Relationship between schizophrenia and cognitive functions has been reported by several studies. Our work group examined the changes of cognitive functions in prepsychotic patients without any relevant psychiatric disorder in their anamnesis, and also in schizophrenic patients with predominantly negative symptoms. METHODS: Measures were carried out by Cambridge Neuropsychological Test Automated Battery (CANTAB), a complex computer-based test battery of 13 tests covering a wide range of cognitive functions. 11 prepsychotic (9 male, 2 female) and 14 negative-symptom schizophrenic patients (all male) took part in the study. RESULTS: Prepsychotic patients showed significant (p < 0.05) impairment in the tests of visual memory, spatial recognition memory, spatial working memory and sustained attention. In patients with negative-symptoms significant deficits were also found (p < 0.05) in the delayed matching to sample, the working memory test, and in the intra-extradimensional shift--an analogue of Wisconsin Card Sorting Test. CONCLUSION: The present results show CANTAB may be a useful tool to detect the emergence of psychosis in an early phase, and also it has been found that in schizophrenic patients with predominantly negative symptoms further areas of cognition are also affected. The results may provide a better understanding about the background of the disorder, and the early recognition of the cognitive deficits may help to initiate a specific therapy in proper time. This could result in the slowing of the progression and an improved chance of recovery.

Reduced completed suicide rate in Hungary from 1990 to 2001: relation to suicide methods.

BACKGROUND AND METHOD: Changes in the rate of completed suicides and in the suicide methods used in Hungary between 1990 and 2001 were evaluated using the database of the Hungarian Central Statistical Office. RESULTS: During this period of time, the suicidal mortality rate decreased by 27.9%. A major part (62%) of this decrease was due to the less frequent use of poisonous substances and drug overdose, particularly of psychotropics. CONCLUSION: Beside the more widespread treatment of depression and other mental disorders, the improved safety of pharmacotherapy and the removal of the most toxic pesticides and chemicals from everyday use might have contributed to the reduction of the suicide rate in Hungary.

Cognitive functions in prepsychotic patients.

OBJECTIVE: Cognitive dysfunctions are now widely understood as an essential feature of schizophrenia. A great number of cognitive disturbances have been described in drug-naive first-episode patients as well. The full-blown psychotic symptoms are usually preceded by a longer prodromal period, in which non-specific psychological disturbances are already present. The late prodromal phase is also coined as the prepsychotic state, with attenuated, isolated psychotic symptoms. The aim of the present study was to detect cognitive dysfunctions among young adults at the prepsychotic stage with the use of a standardized computer based cognitive test battery. METHOD: Eleven (9 men, 2 women) young Hungarian adults referred to the Outpatient Clinic of the Department of Psychiatry at the University of Debrecen were studied. The patients were re-evaluated for psychotic symptoms after 12 months. The patients had no history of psychiatric disorders or psychotic episodes and were referred by general practitioners on account of non-specific emotional or behavioural abnormalities. The subjects were asked to perform a series of 13 computerized neuropsychological tests of the Cambridge Neuropsychological Test. The performance of the patients were compared to that of the standardized database of the Cambridge Neuropsychological Test. RESULTS AND DISCUSSION: The performance of the prepsychotic patients was significantly lower compared to the healthy individuals in the paired associate learning (PAL, p<0.001), Spatial recognition memory (SRM, p<0.05), Rapid visual processing (RVP, p<0.05), and Spatial working memory (SWM, p<0.05) tests. CONCLUSION: Cognitive deficits were found mainly in attentional, frontal and prefrontal cognitive functions. These impairments may be present at the early stages of the development of psychosis and the standardized cognitive test battery (CANTAB) might be a useful tool for the detection of early cognitive impairments and provide a rationale for early intervention in individuals at risk of developing psychosis.

[Effect of atypical antipsychotics on metabolism]. / Az atípusos antipszichotikumok hatása az anyagcserére.

The metabolic effect of atypical antipsychotic drugs may manifest itself in weight gain, disturbances in glucose homeostasis and dyslipidemia. One confounding factor is that psychotic disorders themselves make the patients prone to specific metabolic changes. Nevertheless clinical studies have confirmed that atypical anti-psychotic drugs have a different metabolic effect. In the present prospective case-series, four male antipsychotic drug-naive psychiatric patients without any familial history of metabolic disorder were studied. The patients received risperidone or olanzapine monotherapy for 12 weeks; weight, plasma levels of triglyceride, cholesterol, HDL, and fasting glucose were measured in every 4th week. In two patients, oral glucose tolerance test (OGTT) was also performed at days 0 and 56. The average weight gain during the 12-week period was 12%. The cholesterol and triglyceride plasma concentrations were also elevated. The fasting glucose levels did not change during the observation period. In the OGTT performed in two patients, normal fasting glucose and insulin plasma levels were observed after 8 weeks; however, the plasma insulin concentrations were highly elevated after glucose intake, which may suggest the presence of insulin resistance. Our preliminary results confirmed the previous results on the metabolic effect of atypical anti-psychotic drugs, which may lead to metabolic syndrome. The regular control of the metabolic laboratory parameters, early intervention and the modification of the atypical antipsychotic treatment may help to avoid this adverse effect of the drugs.

Serum paraoxonase activity changes in patients with Alzheimer's disease and vascular dementia.

The prevalence of Alzheimer's disease (AD) and vascular dementia (VAD) increases with aging of the population. The role of lipoproteins in the pathogenesis of AD is unclear: apoE(2) offers protection and apoE(3) is neutral, while apoE(4) promotes the development of the disease. Recently, several studies have confirmed the role of oxidative stress in the pathogenesis of AD and VAD. HDL-associated paraoxonase is one of the antioxidative enzymes that may reduce LDL oxidation. In our study, we investigated the lipid parameters of the sera and the serum paraoxonase activity in patients with AD and VAD. Lipid parameters were determined by an autoanalyzer in 30 AD patients, 40 VAD patients and 40 healthy, age-matched control (C) subjects. Paraoxonase activity was measured spectrophotometrically using paraoxon as the substrate. The phenotypic distribution of paraoxonase was determined by the dual substrate method, using paraoxon and phenylacetate as substrates. In our results, we found that most of the patients with AD had the apoE(4) isoform, consistent with other studies. In the VAD and AD patients we found significantly higher total-cholesterol compared to the control group (C: 4.71 +/- 0.89, VAD: 6.3 +/- 0.8, AD: 6.52 +/- 0.7 mmol/l; p < 0.01) and LDL-cholesterol levels (C: 2.6 +/- 0.6, VAD: 3.96 +/- 0.8, AD: 3.84 +/- 0.6 mmol/l; p < 0.001). The HDL-associated antioxidant, paraoxonase activity did not differ significantly in the patient groups, but compared to the healthy control subjects, paraoxonase activity was significantly lower in both of the patient groups (C: 188 +/- 55 U/l; AD: 131 +/- 37, VAD: 151 +/- 50 l; p < 0.05). Our results suggest that the defect in HDL-associated antioxidant capacity plays a role in the pathogenesis of Alzheimer's disease and vascular dementia.

[Use of positron emission tomography in psychiatry]. / A pozitronemissziós tomográfia pszichiátriai alkalmazása.

For the past years, substantial amount of experimental data has been published on the use of positron emission tomography in different psychiatric disorders. The different PET methods, which evaluate the whole-brain or regional metabolism, tissue perfusion or receptor density may help to identify the disorder specific changes in brain function and also better understand the underlying pathophysiology. In the clinical practice, PET plays an important role in the diagnosis and differential diagnosis of dementias and, presumably, in the near future the PET technique will be also extensively used in the clinical examination of other psychiatric disorders.

[Auditory event related potential and PET scan: a possibility for the comprehensive evaluation of cognition]. / Auditoros eseményhez kötött potenciál és PET: lehetóség a kogníció folyamatának komplex megközelítésére.

The authors studied the parallel use of event related potential (ERP) and brain activation PET in nine healthy volunteers. The presence of P300 wave in the EEG recording was accompanied by a parallel increase in the blood perfusion of the anterior cingulate gyrus. Furthermore, the functional connectivity between cortical and subcortical structures was also present during the task. This method combines the fine temporal-resolution of ERP and spatial-resolution of PET, which allows for the complex examination of fast cognitive processes. This approach may be useful in the investigation of psychiatric disorders.