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H Beckmann

Publications and source records attributed to H Beckmann.

At least 55 records · Page 3Linked to original sources
PubMed1996

Specific P300 features in patients with cycloid psychosis.

In previous studies, low amplitudes and asymmetrical topography with right-sided peaks of the P300-evoked response have been repeatedly described in schizophrenic patients. A total of 18 patients with cycloid psychosis fulfilling the criteria of Perris and Brockington and 18 controls were investigated with a standard auditory odd-ball paradigm and multichannel-evoked potential recordings. Patients had normal P300 topographies and latencies but significantly higher amplitudes than controls. Higher than normal P300 amplitudes have not been described in any other psychiatric disorder until now, and indicate an enhanced level of arousal. Future studies are expected to shed light on the question of whether high P300 amplitudes are transitory sequelae of the acute psychotic episode or a trait of cycloid psychosis.

Adult↗
PubMed1996

Gene-environment interaction in schizophrenia: season-of-birth effect reveals etiologically different subgroups.

Compared to the general population, one consistent finding in schizophrenia research is a significant surplus of schizophrenic births in the winter/spring months. There is little evidence that this is attributed to statistical artefacts. The "harmful effects' hypothesis offers the most plausible explanation for this phenomenon. Exogenous harmful effects, predominant during the cold season, may affect the developing immature fetal brain and thus constitute some of the factors predisposing to schizophrenic breakdown in adulthood. Neuropathological and epidemiological studies point to the second trimenon of gestation as the crucial period of fetal brain maturation. Recently, some studies found that the surplus in schizophrenic winter/spring births is mainly due to sporadic forms. In contrast, patients with high genetic risk of the disease even tended to have a birth deficit during this period. This suggests that schizophrenia is not a disease entity but consists of etiologically distinct subgroups on which the influence of genes and/or environment has to be weighted differently. On the one hand, in sporadic forms of the disease exogenous noxious agents may be of major etiological importance. On the other hand, in fetuses at high genetic risk neurodevelopment may already be disturbed due to a genetic defect and additional environmentally noxious agents can cause abortions, stillbirths and sudden infant deaths.

Embryonic and Fetal Development↗
PubMed1996

[Genetic heterogeneity of schizophrenia. Results of a systematic twin study].

One reason for the inconsistent findings in schizophrenia research is the lack of diagnostic conformity. In the face of modern operational "atheoretical" diagnostic systems, this dilemma is still present. In order to examine specificity and validity of diagnoses, we carried out a systematic twin study with index twins suffering from schizophrenic spectrum psychoses. We compared the diagnostic systems of DSM-III-R, which is based on consensus of international experts, with Leonhards' nosology developed on sophisticated clinical observation and description of psychopathological phenomena occurring during the long-term course of psychiatric diseases. We examined twin concordance, family history, and the frequency and severity of complications of pregnancy and child-birth. The results suggest that the schizophrenic spectrum has to be divided into clinically and etiologically heterogeneous subgroups. This was much more striking when Leonhard's diagnostic criteria were used than with DSM-III-R diagnostic criteria. There seem to be three valid and etiologically different groups: cycloid psychoses, unsystematic schizophrenias and systematic schizophrenias as proposed by Leonhard. In cycloid psychoses genetic loading seems to be low (proband concordance MZ 38%, DZ 29%), but pregnancy and birth complications may have an important role in the etiology. On the other hand, unsystematic schizophrenias are obviously predominantly inherited (proband concordance MZ 88%, DZ 17%) and "environmental" factors are not very prominent. It is striking that MZ twins with a diagnosis of systematic schizophrenia have not yet been found, whereas 32% of DZ index twins (6 out of 19) were diagnosed as having systematic schizophrenia. Further, all DZ twins with the diagnosis of systematic schizophrenia were discordant and the affected twins had threetimes as many and as severe pregnancy and birth complications in the history than their healthy co-twins.

Adult↗
PubMed1995

Coactivator and promoter-selective properties of RNA polymerase I TAFs.

Human ribosomal RNA synthesis by RNA polymerase I requires the activator UBF and the promoter selectivity factor SL1, which consists of the TATA binding protein (TBP) and three associated subunits, TAFI110, TAFI63, and TAFI48. Here it is shown that both TAFI110 and TAFI63 contact the promoter, whereas TAFI48 serves as a target for interaction with UBF and is required to form a transcriptionally active SL1 complex responsive to UBF in vitro. TAFI48 also alters the ability of TBP to interact with TATA box elements, and the resulting complex fails to support transcription by RNA polymerase II. Thus, TAFI48 may function both as a target to mediate UBF activation and as a class-specific promoter selectivity factor.

DNA-Binding Proteins↗
PubMed1995

Evidence against unusual sex concordance and pseudoautosomal inheritance in the catatonic subtype of schizophrenia.

The study is based on sibships with multiply afflicted members derived from a family study of consecutively admitted probands with catatonic schizophrenia. As shown recently, the clinical subtype of periodic catatonia, as defined by Leonhard, is compatible with a major gene effect and genetic anticipation; that is, the age of illness onset of the probands is significantly earlier than that of their parents. In the present study, 83 probands with the clinical subtype of periodic catatonia had 26 afflicted siblings that were distributed among 23 families. We analyzed sex-concordance and pseudoautosomal inheritance patterns. Stratifying the 26 afflicted siblings by sibship size and by the proband's sex, we did not find unusual sex-concordance rates in sibships afflicted with periodic catatonia. Further, there was no association between sex concordance and maternal or paternal origin of the disease. Thus, our results provide strong evidence against pseudoautosomal inheritance or sex-linked transmission in affected sibships in the obviously familial schizophrenic subtype of periodic catatonia.

Adult↗
PubMed1995

Reduced echogenicity of brainstem raphe specific to unipolar depression: a transcranial color-coded real-time sonography study.

Echogenicity of the brainstem raphe was assessed in patients with major depression, bipolar affective disorders, and schizophrenia and compared with healthy adults employing transcranial color-coded real-time sonography. Forty probands were enrolled in each group. A highly significant reduction in raphe echogenicity was detected only in patients suffering from major depression. Echogenicity of the raphe was independent of age or sex and did not correlate with severity of the depressive syndrome or patient state. These findings are suggestive of structural desintegration of the brainstem raphe in unipolar depression, an anatomical region assumed to be a biological focus in the pathogenesis of depressive syndromes.

Adult↗
PubMed1995

Regional differences in the interaction of the excitotoxins domoate and L-beta-oxalyl-amino-alanine with [3H]kainate binding sites in human hippocampus.

The excitotoxic amino acid domoate causes anterograde amnesia and memory deficits while the excitotoxin L-beta-oxalyl-amino-alanine (L-BOAA) is considered the causative agent of the motoneurone disorder, neurolathyrism. Employing quantitative autoradiography we investigated the potency of domoate and L-BOAA to inhibit [3H]kainate binding in human hippocampus. Domoate inhibited binding of [3H]kainate with inhibition constants between 5.8 +/- 2.8 nM (deep layers of gyrus parahippocampalis) and 200.9 +/- 247.8 nM (CA1 region of hippocampus). It was about a thousandfold more potent than L-BOAA with inhibition constants between 2.1 +/- 0.5 microM (superficial layers of gyrus parahippocampalis) and 51.0 +/- 41.9 microM (CA2/3 region of hippocampus). Interestingly, L-BOAA showed lowest affinity to [3H]kainate binding sites in those regions in which domoate showed highest affinity (e.g. CA2/3) and vice versa (e.g. CA1). These data further support the notion that the neurological symptoms observed after domoate intoxication are due to an excitotoxic action at kainate receptors and provide evidence for heterogeneity of kainate receptors in human hippocampus.

Aged↗
PubMed1995

Consensus on minimal criteria of clinical and neuropathological diagnosis of schizophrenia and affective disorders for post mortem research. Report from the European Dementia and Schizophrenia Network (BIOMED I).

The sophisticated analysis of and growing information on the human brain requires that acquisition, dissection, storage and distribution of rare material are managed in a professional way. In this publication we present the consensus of the European work group "European Dementia and Schizophrenia Network", granted by the BIOMED I project of the EU, on minimal neuropathological and clinical requirements to include brains of patients with schizophrenia and affective disorders in post mortem studies. The description of clinical prerequisites in different EU countries and institutions is followed by a consensus on tissue handling, a consensus on minimal neuropathological criteria and a consensus on minimal clinical diagnostic criteria including clinical vignette, family, social, education/professional and general medical histories, general physical history including neurostatus, neurological, psychiatric, medication and general pathological histories, psychostatus, laboratory tests and a history provided by family/health care giver questionnaire. This publication should give help to interconnect different European brain bank centers on a basis of standardized protocols.

Brain↗
PubMed1995

Periodic catatonia: a schizophrenic subtype with major gene effect and anticipation.

In a family study involving 139 probands with DSM-III-R catatonic schizophrenia and 543 first-degree relatives, we investigated age-specific morbidity risk according to Leonhard's clinical distinction between systematic and periodic catatonia. This dichotomy is based on different types of symptomatology, course, and outcome. In systematic catatonia the age-corrected morbidity risk was 4.6%. In periodic catatonia, however, there was an age-corrected morbidity risk with homogenous psychoses of 26.9%, and more parents than siblings were affected. This points strongly to a major gene effect in periodic catatonia. Furthermore, a pairwise comparison of patients and their parents revealed patterns of anticipation, i.e., the probands' age at the onset of disease was significantly earlier than that of their parents (P < 0.001). Similarly, anticipation was apparent in pedigrees with three successive generations affected. This inheritance pattern with homogenous psychoses and anticipation indicates that genes with trinucleotid repeat expansion or other repetitive elements affecting gene expression may be involved in the etiology of periodic catatonia. Thus, periodic catatonia as a specific clinical subtype of schizophrenia is a promising candidate for molecular genetic evaluation.

Adult↗
PubMed1995

Decreased catalase activity but unchanged superoxide dismutase activity in brains of patients with dementia of Alzheimer type.

"Oxidative stress" may be of significance in the etiopathogenesis of dementia of Alzheimer type (DAT). Therefore, we measured activities of the enzymes superoxide dismutase (SOD) and catalase (CAT), which detoxicate reactive oxygen species. Enzyme activities were measured postmortem in basal ganglia, cortical, and limbic brain regions of patients with DAT and age-matched controls. SOD activity increased with age in basal nucleus of Meynert. However, there was no significant difference in SOD activity between DAT and controls. CAT activity was independent of age and postmortem time. There were significant reductions in CAT activity in parietotemporal cortex, basal ganglia, and amygdala in DAT compared with controls (p < 0.05 to 0.01). Our findings are in line with the assumption that reactive oxygen species could contribute to the pathogenesis of DAT. Absence of these changes in basal nucleus of Meynert might reflect retrograde degeneration of cholinergic fibers.

Age Factors↗
PubMed1994

Reconstitution of transcription factor SL1: exclusive binding of TBP by SL1 or TFIID subunits.

RNA polymerase I and II transcription factors SL1 and TFIID, respectively, are composed of the TATA-binding protein (TBP) and a set of TBP-associated factors (TAFs) responsible for promoter recognition. How the universal transcription factor TBP becomes committed to a TFIID or SL1 complex has not been known. Complementary DNAs encoding each of the three TAFIs that are integral components of SL1 have not been isolated. Analysis of subunit interactions indicated that the three TAFIs can bind individually and specifically to TBP. In addition, these TAFIs interact with each other to form a stable TBP-TAF complex. When TBP was bound first by either TAFI110, 63, or 48, subunits of TFIID such as TAFII250 and 150 did not bind TBP. Conversely, if TBP first formed a complex with TAFII250 or 150, the subunits of SL1 did not bind TBP. These results suggest that a mutually exclusive binding specificity for TBP intrinsic to SL1 and TFIID subunits directs the formation of promoter- and RNA polymerase-selective TBP-TAF complexes.

Amino Acid Sequence↗
PubMed1994

Assembly of transcriptionally active RNA polymerase I initiation factor SL1 from recombinant subunits.

Initiation of ribosomal RNA synthesis by RNA polymerase I requires the promoter selectivity factor SL1, which consists of the TATA-binding protein, TBP, and three associated factors, TAFIS 110, 63, and 48. Here the in vivo and in vitro assembly of functional SL1 complexes from recombinant TAFIS and TBP are reported. Complexes containing TBP and all three TAFIS were as active in supporting transcription from the human ribosomal RNA gene promoter as endogenous SL1, whereas partial complexes without TBP did not efficiently direct transcription in vitro. These results suggest that TAFIS 110, 63, and 48, together with TBP, are necessary and sufficient to reconstitute a transcriptionally active SL1 complex.

DNA-Binding Proteins↗
PubMed1994

Memantine inhibits [3H]MK-801 binding to human hippocampal NMDA receptors.

The antispastic agent and N-methyl-D-aspartate (NMDA) receptor antagonist memantine has recently been proposed as a neuroprotective drug for use in patients with dementia syndromes with primarily temporal lobe pathology, e.g. senile dementia of Alzheimer type or dementia in Parkinson's disease. In a quantitative autoradiographic study in human post mortem hippocampus, memantine was able to inhibit binding of the noncompetitive NMDA-antagonist [3H]MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine maleate) with inhibition constants between 3 and 10 microM, being about a factor of 10 more potent than the dissociative anaesthetic and NMDA receptor antagonist (+/-)ketamine. As these inhibition constants are well within the therapeutic concentration range of memantine, antagonism of endogenous glutamate at limbic NMDA receptors may be one molecular mechanism by which memantine is beneficial in dementia syndromes.

Aged↗
PubMed1994

Excitotoxins L-beta-oxalyl-amino-alanine (L-BOAA) and 3,4,6-trihydroxyphenylalanine (6-OH-DOPA) inhibit [3H] alpha-amino-3- hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) binding in human hippocampus.

Excitotoxins L-beta-oxalyl-amino-alanine (L-BOAA) and 3,4,6-trihydroxyphenylalanine (6-OH-DOPA) have been investigated with regard to their potency to inhibit [3H] alpha-amino-3-hydroxy-5-methyl-4- isoxazole-propionic acid (AMPA) binding in human hippocampus in a quantitative autoradiographic study. With dissociation constants (KD) of [3H]AMPA binding and inhibition concentrations (IC50) of L-BOAA, 6-OH-DOPA and L-glutamate obtained from saturation and displacement experiments inhibition constants (Ki) for the inhibition of [3H]AMPA binding in individual hippocampal subregions could be calculated. They were between 5.2 +/- 2.9 and 35.1 +/- 39.9 microM for L-BOAA and 39.1 +/- 26.8 and 59.4 +/- 44.1 microM for 6-OH-DOPA. L-BOAA was equally potent as the endogenous agonist L-glutamate with Ki's between 13.1 +/- 3.9 and 21.4 +/- 12.1 microM (n = 4, mean +/- S.D.). Limbic system symptoms like cognitive deficits, mood disturbances and vivid dreams observed in patients with the motor neuron disease neurolathyrism may thus well be mediated by agonistic action of L-BOAA at AMPA glutamate receptors in hippocampus.

Aged↗
PubMed1994

Circumscribed malformation and nerve cell alterations in the entorhinal cortex of schizophrenics. Pathogenetic and clinical aspects.

A postmortem histological comparison of 5 selected cases of schizophrenia with 5 non-schizophrenic controls showed a circumscribed malformation of the entorhinal cortex. The cortical alterations consisted mainly of a lack or a change of the characteristic island formations in layer II pre-alpha. Further, there were atypical neurons in layers II and III showing a conspicuous decrease of volume, often a change of the shape. They lay either in clusters or in columnar formations. These cells were considered "young neurons". The changes varied considerably from case to case and sometimes extended to all entorhinal layers. In one case the extension of the changes is described by means of serial sections in steps which extend over the whole rostral entorhinal region. Here, the striking architectural changes were formed in an exactly circumscribed sector and did not extend to the rostral hippocampal formation. On the whole, the changes are regarded as local migrational disturbances that occur during the second trimester of brain development. Neuronal displacements like these could give rise to various aberrant connections within the limbic system and related structures (e.g. the central position of the entorhinal region in circuits such as the entorhino-hippocampal loop, entorhinol-insula and entorhino-orbitofrontal reciprocal connections). Whereas alterations of the genetic programming of cell migrations may be suspected, various environmental influences (e.g. viral infections during the months III-V of pregnancy) appear to play a significant role. The malformations may be a decisive vulnerability factor for the later manifestation of the illness.

Adult↗
PubMed1994

Triplet repeats in clinical subtypes of schizophrenia: variation at the DRPLA (B 37 CAG repeat) locus is not associated with periodic catatonia.

Clinical evidence for a dominant mode of inheritance and anticipation in periodic catatonia, a distinct subtype of schizophrenia, indicates that genes with triplet repeat expansions or other unstable repetitive elements affecting gene expression may be involved in the etiology of this disorder. Because patients affected with dentatorubral-pallidoluysian atrophy (DRPLA) may present with "schizophrenic" symptoms, we have investigated the DRPLA (B 37 CAG repeat) locus on chromosome 12 in 41 patients with periodic catatonia. The B 37 CAG repeat locus was highly polymorphic but all alleles in both the patient and control group had repeat sizes within the normal range. We conclude that variation at the DRPLA locus is unlikely to be associated with periodic catatonia. The evidence for dominant inheritance and anticipation as well as the high prevalence of human brain genes containing trinucleotide repeats justifies further screening for triplet repeat expansions in periodic catatonia.

Adult↗