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P Falkai

Publications and source records attributed to P Falkai.

At least 19 recordsLinked to original sources
PubMed2001

Amplitude reduction of the mismatch negativity in first-degree relatives of patients with schizophrenia.

First-degree relatives of schizophrenic patients display alterations in various cognitive domains and their electrophysiological counterparts similar to schizophrenic subjects. The mismatch negativity (MMN) is an event-related potential that reflects sensory memory in the pre-attentive stage of auditory processing. An amplitude reduction of the MMN has been reported in schizophrenia. The present study investigated the MMN in patients with schizophrenia, first-degree relatives and control subjects. The MMN amplitude was reduced in relatives compared to controls. The MMN amplitude reduction in schizophrenic patients compared to controls, however, did not reach significance in the present study. These results provide first evidence for disturbed sensory memory in relatives of patients with schizophrenia.

Adult↗
PubMed2001

Mind reading: neural mechanisms of theory of mind and self-perspective.

Human self-consciousness as the metarepresentation of ones own mental states and the so-called theory of mind (TOM) capacity, which requires the ability to model the mental states of others, are closely related higher cognitive functions. We address here the issue of whether taking the self-perspective (SELF) or modeling the mind of someone else (TOM) employ the same or differential neural mechanisms. A TOM paradigm was used and extended to include stimulus material that involved TOM and SELF capacities in a two-way factorial design. A behavioral study in 42 healthy volunteers showed that TOM and SELF induced differential states of mind: subjects assigned correctly first or third person pronouns when providing responses to the stimuli. Following the behavioral study, we used functional magnetic resonance imaging (fMRI) in eight healthy, right-handed males to study the common and differential neural mechanisms underlying TOM and SELF. The main factor TOM led to increased neural activity in the anterior cingulate cortex and left temporopolar cortex. The main factor SELF led to increased neural activity in the right temporoparietal junction and in the anterior cingulate cortex. A significant interaction of both factors TOM and SELF was observed in the right prefrontal cortex. These divergent neural activations in response to TOM and SELF suggest that these important differential mental capacities of human self-consciousness are implemented at least in part in distinct brain regions. Press

Adult↗
PubMed2001

[Structural brain changes in patients with schizophrenic psychoses. From focal pathology to network disorder].

Schizophrenia is a brain disorder characterized by a heterogeneous clinical symptomatology. Accordingly, many structural brain changes are not associated directly with clinical symptoms. These structural changes can be detected in the frontotemporal cortex and may correlate with the course of the disease. The most important etiological concept is the neurodevelopmental hypothesis according to which developmental, morphologically detectable changes predispose for the acquisition of schizophrenia. The relevance of neurodegenerative components also remains to be determined. However, it is becoming increasingly clear that schizophrenia is not associated with pathological changes in a circumscribed brain region but with widely distributed morphological changes. Presently, the leading hypothesis for explaining these changes is a frontotemporolimbic network disturbance with cytoarchitectural changes in the heteromodal association cortex. Present research therefore focuses on testing this theory using functional imaging on a macroscopic level and examination of the neuronal cytoarchitecture on a microscopic level.

Brain↗
PubMed2001

[Prevalence and clinical significance of computerized tomography verified idiopathic calcinosis of the basal ganglia].

With increasing CT examinations of the cerebrum, the discovery of basal ganglia calcification becomes more frequent. In order to correlate these calcifications to the symptoms believed to be accompanied with Fahr's disease 2318 cranial CT scans were examined. There was an overall incidence of basal ganglia calcification of 12.5%. The most frequent location was the globus pallidus (96.4%). In the examined population there was no correlation found between the calcifications and symptoms having been described with striopallidentate calcifications.

Aged↗
PubMed2001

Right frontal hypergyria differentiation in affected and unaffected siblings from families multiply affected with schizophrenia: a morphometric mri study.

OBJECTIVE: The authors used magnetic resonance imaging to corroborate the postmortem finding of right frontal hypergyria associated with schizophrenia. METHOD: Twelve affected-unaffected sibling pairs from families multiply affected with schizophrenia were studied. Bilateral measurement of the gyrification index, the ratio of the inner and outer surface contours, was performed on three different slices of the prefrontal region. RESULTS: The mean gyrification index on the right side was significantly higher in siblings with schizophrenia or schizoaffective disorder than in the unaffected siblings. CONCLUSIONS: In this family cohort study, the postmortem finding of right-sided hypergyria in subjects with schizophrenia was replicated in vivo with magnetic resonance imaging. This observation provides further support for a neurodevelopmental mechanism in the pathogenesis of schizophrenia.

Adult↗
PubMed2000

Decreased frontal lobe ratio of N-acetyl aspartate to choline in familial schizophrenia: a proton magnetic resonance spectroscopy study.

Neuropathological and neuroimaging studies suggest neuronal dysfunction in schizophrenia. N-acetyl aspartate (NAA) is a useful marker of neuronal dysfunction that can be measured with magnetic resonance spectroscopy (MRS). In the present study NAA, choline (Cho), phospho-creatine ((P)Cr), inositol containing compounds and glutamine/glutamate (Glx) were assessed in the left frontal lobe and basal ganglia of subjects with familial schizophrenia, family members with mixed psychiatric diagnoses, unaffected family members, and community controls. Concentrations of metabolites were analyzed and expressed as ratios. NAA/Cho, NAA/(P)Cr and Glx containing compounds showed a negative correlation with age in the frontal lobe. After covarying for age, subjects with schizophrenia had a significant reduction in the left frontal lobe NAA/Cho ratio compared with unaffected family members (P=0.018) as well as with community non-familial (P=0.037) controls. These MRS observations support the hypothesis of a disease-related neuronal deficit in the frontal lobe of schizophrenic patients, and relatively normal basal ganglia.

Adult↗
PubMed2000

Entorhinal cortex pre-alpha cell clusters in schizophrenia: quantitative evidence of a developmental abnormality.

BACKGROUND: Previous studies using semiquantitative or qualitative techniques demonstrated abnormalities of positioning of clusters of neurons (pre-alpha cells) in the entorhinal cortex in schizophrenia, suggesting a developmental mechanism could contribute to the illness. Recent quantitative studies of laminar thickness and laminar cell counts have been less consistent, and several failed to replicate the finding. However, none of the quantitative studies focused on the position of the pre-alpha cell clusters. METHODS: To study pre-alpha cell position in detail, we examined the entorhinal cortex in serial sections from 21 control and 19 schizophrenic brains. Cluster position relative to the gray-white matter junction and cluster size were measured. RESULTS: Quantitative assessment of 1991 clusters indicated clusters were positioned relatively closer to the gray-white matter junction in the anterior half of schizophrenic entorhinal cortices. In addition, the size of clusters in males with schizophrenia was reduced. CONCLUSIONS: These results support the model of schizophrenia as an illness in which brain development is impaired. The findings in males with schizophrenia may indicate the presence of more severe pathology, or an additional pathogenic mechanism.

Adult↗
PubMed2000

Antidepressant drug exposure is associated with mRNA levels of tyrosine receptor kinase B in major depressive disorder.

1. Recent studies have provided support for the notion that the high affinity neurotrophin receptor tyrosine receptor kinase B (trk B) may be involved in the treatment of depression. 2. Using a quantitative RT-PCR approach trk B mRNA levels were determined in brain material from cerebellum, temporal cortex, and frontal cortex of control specimen and patients with major depressive disorder, schizophrenia and bipolar disorder (15 subjects each). 3. Interestingly, elevated trk B mRNA levels were found in cerebellum (3.6-fold) in patients with major depressive disorder, reaching statistical significance (p=0.03). 4. The major depressive disorder-on drugs group differed from controls (p=0.006) in the cerebellum. 5. Since only patients with major depressive disorder received antidepressants, elevated trk B mRNA levels are possibly related to drug treatment.

Adult↗
PubMed2000

Automated image analysis of disturbed cytoarchitecture in Brodmann area 10 in schizophrenia: a post-mortem study.

1. Among different etiological concepts in schizophrenia research is the disconnect on hypothesis involving distributed brain regions. Adequate empirical research requires correlational studies of multiple brain regions. In this pilot study, the authors therefore tested the applicability of an automated image analysis device as a scanning tool to detect cytoarchitectural abnormalities in Brodmann area (BA) 10. 2. The authors applied the gray level index (GLI) method as automated image analysis on 10 schizophrenic brains compared to 10 controls. The GLI as perikarya-neuropil-ratio is obtained as the ratio between the area covered by cellular cross sections and the area of the total measuring field in 101 continous measuring fields from pial surface to the cortical depth. Resulting data provide a specific cytoarchitectonic profile curve. An analysis was performed separately for mean GLI and GLI values in six compartments covering approximately the different cortical laminae. 3. A statistically significant reduction of the mean GLI was demonstrated in the schizophrenic group covering laminae III to VI, as detected by multivariate analysis and corroborated by univariate analyses and t-tests. 4. This result clearly underlines a cytoarchitectonic disturbance with a perikarya neuropil-ratio reduction in BA 10, that is associated with schizophrenia. This is suggestive either of an increased neuropil fraction or a decreased neuronal perikarya fraction. The latter could either be due to a volume or a total number reduction of neuronal perikarya. These data are compatible with previously published data on cell loss in schizophrenics in BA 10.

Autopsy↗
PubMed2000

Vagus nerve stimulation is associated with mood improvements in epilepsy patients.

Vagus nerve stimulation (VNS) has gained increasing acceptance for treatment of drug-resistant seizures. The aim of this study was to evaluate effects of VNS on depressed mood in epilepsy patients during the first 6 months after implantation of the stimulation device. This study was conducted as an addition to the international multisite randomized and double-blind controlled trial on anti-seizure effects of VNS (EO3). Only adult patients with >4/month medication-resistant complex-partial seizures were included (N=11). During the acute phase of the study (3 months after implantation), patients were randomly assigned to low (stimulation detection) versus high stimulation (maximal tolerability, maximum 1.75 mA). Mood and mood changes were recorded based on standardized psychiatric rating scales and self-report questionnaires. Patients were assessed 4 weeks before (baseline) as well as 3 and 6 months after implantation. Significant positive mood effects were observed in most scales and subscales at the 3-month follow-up (P<0.05). Mood improvements were sustained at the 6-month follow-up and were independent of effects on seizure activity (9/11 mood responders versus 2/11 seizure responders). Mood effects appeared more pronounced in the high stimulation group after the acute study phase, but findings were not significant (P<0.10). VNS is associated with mood improvements in patients with epilepsy, but to confirm VNS dose effects, studies with more statistical power are needed.

Adult↗
PubMed2000

A genome-wide autosomal screen for schizophrenia susceptibility loci in 71 families with affected siblings: support for loci on chromosome 10p and 6.

Evidence from epidemiological studies and segregation analysis suggests oligo- or polygenic inheritance in schizophrenia. Since model independent methods are thought to be most appropriate for linkage analysis in complex disorders, we performed a genome-wide autosomal screen in 71 families from Germany and Israel containing 86 independent affected sib-pairs with parental genotype information for statistical analysis strictly identity by descent. We genotyped 305 individuals with 463 markers at an average distance of approximately 10 cM genome-wide, and 1-2 cM in candidate regions (5q, 6p, q, 8p, 10p, 18p, 22q). The highest multipoint LOD scores (ASPEX) were obtained on 6p (D6S260, LOD = 2.0; D6S274, LOD = 2.2, MHC region, LOD = 2.15) and on 10p (D10S1714, LOD = 2.1), followed by 5q (D5S2066, LOD = 1.36), 6q (D6S271, LOD = 1.12; D6S1613, LOD = 1.11), 1q (D1S2675, LOD = 1.04), and 18p (broad disease model: D18S1116, LOD = 1.0). One hundred and thirty-three additional family members were available for some of the families (extended families) and were genotyped for these regions. GENEHUNTER produced a maximum NPL of 3.3 (P = 0.001) for the MHC region and NPL of 3.13 (P = 0.0015) for the region on 10p. There is support for these regions by independent groups. In genome-wide TDT analysis (sTDT, implemented in ASPEX), no marker passed the significance level of 0.0001 given by multiple testing, but nominal significance values for D10S211 (P = 0.03) and for GOLF (P = 0.0032) support further the linkage results on 10p and 18p. Our survey of 22 chromosomes identified candidate regions which should be useful to screen for schizophrenia susceptibility genes.

Chromosome Mapping↗
PubMed2000

Disturbed gyrification of the prefrontal region in male schizophrenic patients: A morphometric postmortem study.

OBJECTIVE: The goal was to test the hypothesis that abnormalities of gyrification are present in the prefrontal region of postmortem brains from schizophrenic patients. METHOD: The authors compared the prefrontal regions in brains from 24 schizophrenic patients and 24 normal comparison subjects. The gyrification index, the ratio of inner and outer surface contours, was measured bilaterally in three different slices from each brain. Area measurements of gray and white matter were studied separately by planimetric analysis in the same sections. In addition, a gray-to-white-matter ratio and an asymmetry coefficient were computed. RESULTS: The mean gyrification index on the right side was significantly higher in the male schizophrenic patients than in the comparison men. The gyrification index of the female patients was not significantly different from that of the female comparison subjects. Analysis of area measurements revealed no significant differences. CONCLUSIONS: As gyrification is an ontogenetic stable feature unaffected by atrophic processes during aging, the gyrification abnormalities of the prefrontal region provide further evidence of the importance of a neurodevelopmental mechanism in the etiology of schizophrenia, at least in males.

Age Factors↗
PubMed2000

[The chances of new atypical substances].

Antipsychotic treatment with so-called "atypical" neuroleptics, as defined by the lack of extrapyramidal side effects in its strict sense, has made great advances in the last decades with the advent of newly developed antipsychotic agents. The first atypical neuroleptic drug was clozapine, also referred to as "dirty drug" or "rich drug" because of its broad receptor binding profile. Clozapine has been the starting point for several different, newly developed antipsychotics. Among these, the most prominent are olanzapine, risperidone, sertindol, ziprasidone, and amisulpride. All of these newly developed, atypical antipsychotics show a high degree of efficacy in the treatment of positive symptoms of schizophrenia in combination with a lack of or a reduced degree of extrapyramidal side effects (EPS). In addition, several atypical antipsychotics seem to have an additional impact on negative symptoms such as alogia, anhedonia, or avolition. However, apart from the clear advantage of clozapine in the treatment of otherwise treatment-resistant schizophrenia, differential indications for the different antipsychotics remain to be established.

Antipsychotic Agents↗
PubMed1999

Neural expression profile of alpha-synuclein in developing human cortex.

Alpha-synuclein is a predominantly neuronal presynaptic protein that may play an important role during synaptogenesis and CNS development. In order to elucidate the human developmental expression profile, we used a polyclonal antiserum against the NAC domain of alpha-synuclein. In normal fetal cortex neuroectodermal precursor cells elicited staining in the soma, whereas, in adult cortex, we observed a staining pattern compatible with synaptic function. The same developmental intraneuronal redistribution was found in neurodegenerative disorders, i.e. somatic staining in neuroectodermal precursors in fetal (trisomy 21) and a synaptic pattern in adult (Down's syndrome, Alzheimer's disease) brains. RT-PCR and Western blot analysis revealed expression at all time points studied (4-7.5 months) during human brain development.

Adult↗
PubMed1999

Evidence for activation of microglia in patients with psychiatric illnesses.

Activation of microglia/macrophages is a key event in response to pathological changes in the CNS. HLA-DR is a valuable immunohistochemical marker that specifically reacts with activated microglia cells. In order to elucidate a potential role of microgliosis in severe psychiatric illnesses, post-mortem frontal cortex and hippocampus of patients with schizophrenia (n = 14) and affective disorder (n = 6) and control specimens (n = 13) were studied. Additionally Alzheimer's disease cases (n = 8) were included as a human model system with typical neurodegenerative alterations and microglia activation. All patient groups revealed subjects with abundant microglia immunostaining (schizophrenia, three patients; affective disorder, one patient; Alzheimer's disease, four patients) in both gray and white matter. This finding provides evidence for distinct neuropathological changes in brains of patients with schizophrenia and affective disorder. The activation of microglia cells, which represent a major part of the brain immune response, may help to unravel the pathophysiological processes in severe psychiatric illnesses.

Aged↗
PubMed1999

Cortical sulcal enlargement in catatonic schizophrenia: a planimetric CT study.

To determine whether patients with catatonic schizophrenia have specific alterations in brain morphology, internal (ventricles) and external (frontal, temporal, parieto-occipital) components of the cerebrospinal fluid (CSF) spaces were examined morphometrically. Planimetric measurements of computed tomographic (CT) scans from 37 patients with catatonic schizophrenia, 28 patients with hebephrenic schizophrenia, and 39 patients with paranoid schizophrenia, all diagnosed according to DSM-III-R criteria, were compared with separate age- and sex-matched non-psychiatric control groups, respectively. The areas of the frontal sulci, the parieto-occipital sulci, the inter-hemispheric fissure, and the lateral and third ventricles were measured separately for the right and left hemispheres. Catatonic patients showed significant enlargements in almost all CSF spaces, especially in the left fronto-temporal area which, in addition, correlated significantly with illness duration. Hebephrenic patients showed selective enlargements in left temporal and left/right lower frontal cortical sulci, whereas paranoid schizophrenic patients showed no enlargements but significant correlations between left temporal cortical sulcal volume and illness duration. Alterations in temporal cortical areas were present in all three sub-types of schizophrenia. In addition to temporal alterations, hebephrenic schizophrenia was characterised by lower frontal (i.e. orbitofrontal) enlargement. Catatonic schizophrenia, the most severe sub-type with regard to clinical symptomatology and brain pathology, showed fronto-parietal cortical alterations.

Adult↗
PubMed1999

Alpha-synuclein accumulates in Lewy bodies in Parkinson's disease and dementia with Lewy bodies but not in Alzheimer's disease beta-amyloid plaque cores.

A growing body of evidence suggests that the non-Abeta component of Alzheimer's disease amyloid precursor protein (NACP) or alpha-synuclein contributes to the neurodegenerative processes in Alzheimer's disease (AD), Parkinson's disease (PD) and dementia with Lewy bodies (DLB). In the present study antisera to the N terminus and the NAC domain of the alpha-synuclein protein were employed to elucidate the expression pattern in brains of patients with AD, PD, DLB and control specimen. Alpha-synuclein exhibited an overall punctuate expression profile compatible with a synaptic function. Interestingly, while Lewy bodies were strongly immunoreactive, none of the alpha-synuclein antisera revealed staining in mature beta-amyloid plaques in AD. These observations suggest that alpha-synuclein does not contribute to late neurodegenerative processes in AD brains.

Alzheimer Disease↗