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Biomedical subjects

B Andresen

Publications and source records attributed to B Andresen.

At least 19 recordsLinked to original sources

Mood, cognition and serotonin transporter availability in current and former ecstasy (MDMA) users.

RATIONALE: Chronic recreational ecstasy (MDMA) use has often been reported to be associated with psychopathology, memory impairments and serotonergic alterations. However, the findings have not been consistent. OBJECTIVES: To attempt to replicate these findings, to investigate whether such alterations would be reversible and whether they could be predicted by parameters of previous drug use. METHODS: In a cross-sectional design, 30 current and 31 ex-ecstasy users with ecstasy abstinence of at least 5 months, and 29 polydrug and 30 drug-naive controls were compared on measures of psychopathology, cognitive performance and serotonin transporter availability. RESULTS: The groups did not differ significantly in age, gender distribution, education level and premorbid intelligence. The ecstasy groups did not differ significantly from polydrug controls on most of the relevant parameters of concomitant illegal drug use. Reported drug use was confirmed by hair and urine analyses. All three groups of drug users exhibited significantly elevated psychopathology compared with drug-naive controls. Only ex-ecstasy users were significantly impaired on verbal recall. Current ecstasy users showed significantly reduced distribution volume ratios of serotonin transporter availability in the mesencephalon and caudate nucleus. Regression analyses indicated that psychopathology and serotonergic alterations were best predicted by the number of ecstasy tablets taken on a typical event. CONCLUSION: The results indicate that verbal memory impairments were possibly aggravated after prolonged ecstasy abstinence while there was tentative evidence of serotonergic recovery. On the other hand, self-reported elevated psychopathology appeared to be associated with polydrug use in general and not specifically with ecstasy use.

Adult↗

Specific neurotoxicity of chronic use of ecstasy.

The use of the illicit drug ecstasy (mainly containing methylenedioxymethamphetamine, MDMA) is widespread among young people in western Nations. Animal experiments indicate that MDMA is a potent neurotoxin specifically affecting the serotonergic system. A few functional neuroimaging studies revealed central nervous alterations after the repeated use of ecstasy. We examined 94 ecstasy users in comparison to 27 control subjects by means of positron emission tomography (PET) with 2-[18F]-fluoro-2-deoxy-D-glucose (FDG). The FDG uptake rates were globally reduced in ecstasy users, most pronounced in the striatum. The uptake rates tended to be negatively correlated with the cumulative ecstasy doses. The results indicate that younger ecstasy users may be more vulnerable with regard to neurotoxicity.

Adolescent↗

Improvement of schizophrenic patients' subjective well-being under atypical antipsychotic drugs.

Recent research indicates that subjective well-being is a major determinant of medication compliance in schizophrenia. However, it is yet unresolved whether atypical neuroleptics differ regarding subjective side-effects. A self-report instrument has been constructed to evaluate 'subjective well-being under neuroleptics' (SWN). The primary aims of the present study were to develop a short form of the SWN and to investigate the extent to which the atypical antipsychotic improves the patient's subjective well-being. The short form of the SWN was constructed following an item analysis based on data from 212 schizophrenic patients medicated with either typical or atypical antipsychotics. The short form of the SWN showed sufficient internal consistency and good construct validity. The SWN was only moderately correlated with positive and negative syndrome scale (PANSS) scores or changes in psychopathology (r=-0.20 to -0.37). SWN-ratings in patients receiving olanzapine were superior compared to those of patients medicated with either clozapine or risperidone on three of five domains of well-being. Clozapine reduced global psychiatric symptoms significantly more than risperidone. It is concluded that the assessment of subjective well-being under antipsychotic treatment provides an independent outcome measure which is relevant to compliance.

Adult↗

Negative priming in schizophrenia: effects of masking and prime presentation time.

Beech et al. [Br. J. Clin. Psychol. 28 (1989) 109--116] previously reported attenuated negative priming in schizophrenic patients that was interpreted as a sign of dysfunctional cognitive inhibition. However, subsequent research has provided mixed results. In the present study, it was investigated whether reduced negative priming in schizophrenics may be an experimental artifact. Based on evidence from backward masking studies in schizophrenia, it was hypothesized that brief prime presentation times and pattern masking as used by Beech et al. and others may have impaired the visual perception of the prime display in schizophrenics. 20 schizophrenic patients and 20 matched healthy controls participated in the study. Subjects completed four negative priming experiments varying in prime presentation time (100 or 250 ms) and masking (a mask or a blank screen followed prime presentation). In line with prediction, reduced negative priming in schizophrenics only occurred for trials with 100 ms prime presentation time followed by a mask. Neither psychopathology nor any sociodemographic variable correlated substantially with negative priming. Results strongly suggest that reduced negative priming in schizophrenics may not be due to reduced cognitive inhibition but mirrors perceptual deficits.

Adult↗

Enhanced semantic priming in thought-disordered schizophrenic patients using a word pronunciation task.

Previous research on semantic priming in schizophrenia has produced contradictory findings. For the present study, it was intended to resolve some of the ambiguities in the literature. Using a semantic priming task with word pronunciation, evidence is provided that thought-disordered schizophrenic (TD) patients exhibit significantly increased semantic priming as compared to healthy and psychiatric controls. Results suggest that enhanced semantic priming is not confined to tasks that require lexical decision. Moreover, results indicate that TD schizophrenic patients suffer from a decay of hierarchical thinking, i.e. TD schizophrenics reveal a tendency to process the less meaningful rather than the dominant aspects of external information. Priming effects for the inferior meaning of homograph words (for example, 'dance' is an inferior, and 'game' is a superior associate of the word 'ball') were significantly greater compared to healthy controls and non-TD schizophrenics. Results were not moderated by sociodemographic background variables, psychomotor slowing and psychopathological symptoms other than thought disorder.

Adult↗

An analysis of the specificity and the syndromal correlates of verbal memory impairments in schizophrenia.

It was investigated whether schizophrenic and depressive patients show a distinguishable mnestic profile. A further aim was to explore the psychopathological correlates of memory malperfomance in schizophrenic patients. For the present study, schizophrenic, depressive and healthy samples (n=25 each) were compared regarding their performance in the Rey Auditory Verbal Learning Test. Subjects' sociodemographic background variables were comparable except for age (entered as a covariate). Depressive and schizophrenic patients performed significantly worse than healthy controls regarding both short-term and long-term free recall as well as recognition. No differences occurred for two parameters reflecting proneness to interference. Negative schizophrenic symptomatology was strongly correlated with memory dysfunction before and after controlling for distractibility. The study supports previous research suggesting that memory impairments in schizophrenia are not an epiphenomenon of deficits in verbal fluency or an attentional impairment. The major deficit in both schizophrenic and depressive patients is inferred to be the capability to learn.

Adult↗

Neuropsychological correlates of schizophrenic syndromes in patients treated with atypical neuroleptics.

There is widespread evidence that schizophrenic symptomatology is best represented by three syndromes (positive, negative, disorganized). Both the disorganized and negative syndrome have been found to correlate with several neurocognitive dysfunctions. However, previous studies investigated samples predominantly treated with typical neuroleptics, which frequently induce parkinsonian symptoms that are hard to disentangle from primary negative symptoms and may have inflated correlations with neurocognition. A newly developed psychopathological instrument called the Positive and Negative and Disorganized Symptoms Scale (PANADSS) was evaluated in 60 schizophrenic patients. Forty-seven participants treated with atypical neuroleptics performed several neurocognitive tasks.A three-factor solution of schizophrenic symptomatology emerged. Negative symptomatology was associated with diminished creative verbal fluency and digit span backward, whereas disorganization was significantly correlated with impaired Stroop, WCST and Trail-Making Test B performance.Data suggest that disorganization is associated with tasks that demand executive functioning. Previous findings reporting correlations between negative symptomatology and neurocognition may have been confounded by the adverse consequences of typical neuroleptics.

Acute Disease↗

'Hyper-priming' in thought-disordered schizophrenic patients.

BACKGROUND: A number of studies have suggested that indirect semantic priming is enhanced in thought-disordered schizophrenics. However, research on direct semantic priming has produced conflicting results. The aim of the present study was to resolve some of the ambiguities of previous findings. METHODS: For the present study, 44 schizophrenic patients were split according to the presence of associative loosening into a positive thought-disordered (TD) and non-positive thought-disordered (NTD) group. Thirty healthy subjects and 36 psychiatric patients served as controls. RESULTS: Schizophrenics displayed increased indirect semantic priming compared with psychiatric controls. When subtyping the sample, TD-patients exhibited significantly enhanced indirect semantic priming compared with healthy and psychiatric controls as well as NTD-patients. Overall slowing was found to be independent of priming effects. Medication, age and chronicity of the schizophrenic illness did not modulate priming. CONCLUSIONS: In line with Spitzer and Maher it is inferred that disinhibited semantic networks underlie formal thought disorder in schizophrenia. For future research, it would be appropriate to: employ indirect semantic priming rather than direct semantic priming conditions; and, pay more attention to potential moderators of the priming effect, most importantly, the prime display duration and the length of the stimulus onset asynchrony.

Adult↗

Regulation of gene expression by muscarinic acetylcholine receptors.

In the brain, muscarinic acetylcholine receptors (mAChRs) are involved in higher cognitive functions including synaptic plasticity and memory. In Alzheimer's disease (AD) patients the cholinergic nervous system is severely damaged. In order to reinforce the cholinergic system, clinical tests were started to use cholinomimetic drugs to treat AD patients. To identify the genes involved in mAChR signalling, we used a differential display approach and found 11 genes that were readily activated by mAChR with 1 hour of activation. These included the transcription factors Egr-1, Egr-2, Egr-3, c-Jun, Jun-D and Gos-3; the growth regulator hCyr61; the signalling factors NGFi-B (nerve growth factor induced gene-B) and Etr101; the unknown gene Gig-2 (for G-protein-coupled receptor induced gene 2); and the acetylcholinesterase gene (ACHE). Our data show that multiple immediate-early genes are under the control of mAChRs, and they suggest that these genes play important roles in coupling receptor stimulation to long-term neuronal responses. The results also suggest a feedback mechanism where up-regulated ACHE expression and accelerated breakdown of acetylcholine (ACh) at the cholinergic synapses limits increases in cholinergic transmission. Three hours after m1 mAChR activation a different pattern of gene expression was demonstrated. It included the novel genes Gig-3 and Gig-4, as well as the LIM-only protein LM04. Like ACHE, these genes are target genes which may be under the control of the above immediate-early genes. Together, our data show that muscarinic receptors induce a complex and sustained pattern of gene expression that may be involved in the regulation of cholinergic transmission as well as the control of cellular functions in post-synaptic cholinergic target cells. These results may contribute to a better understanding of the effects and side effects of cholinomimetic treatment in AD patients.

Alzheimer Disease↗

[Association norms for 68 German homonyms].

Norms for 68 German homophonic homographs were collected in a normal population comprising 100 subjects. Frequency and polarity as well as U-scores (index of ambiguity) are presented. 49 of the words revealed a clear dominance for only one meaning. 7 homophonic homographs were balanced, and for 12 words less than 5% of all associations were given for each of the inferior meanings. Studies 2a and 2b are a replication of previous findings on the resolution of semantic ambiguity. Inhibition effects were revealed for discordant triplet conditions which contained a long interstimulus interval between homograph and target, whereas an (insignificant) facilitation effect occurred for trials with a shorter interval. Results of study 2 are in line with context-sensitive models which claim that after the initial activation of all meanings of a homograph a context-guided process leads to a suppression of context-irrelevant homograph information.

Adult↗

Impaired modulation of the saccadic contingent negative variation preceding antisaccades in schizophrenia.

BACKGROUND: The contingent negative variation (CNV) is considered to reflect prefrontal functioning and can be observed before manual and ocular motor responses. Schizophrenic patients exhibit reduced CNV amplitudes in tasks requiring manual motor responses. A number of studies has also found normal prosaccades, but delayed antisaccades and an augmented rate of erroneous prosaccades during the antisaccade task in schizophrenia. In this study we examined the CNV during pro- and antisaccade tasks in schizophrenic patients and healthy control subjects. METHODS: Data of 17 medicated schizophrenics (ICD-10, F20) and 18 control subjects, matched with patients for age, gender, and education were analyzed. Horizontal pro- and antisaccades were elicited in four blocks, each consisting of 80 trials. Electroencephalogram was recorded from 32 channels with a DC amplifier. RESULTS: Patients exhibited delayed correct responses and more erroneous prosaccades during the antisaccade task than control subjects, but normal prosaccadic reaction times. In control subjects, the vertex-predominant saccadic CNV was generally larger than in patients, and larger during the anti- than during the prosaccade task. This task-related amplitude augmentation was absent in patients. Analyses of additional components suggested specificity of impaired event-related potential modulation to the saccadic CNV. CONCLUSIONS: In accordance with the presumed prefrontal dysfunction, our results suggest deficient preparation and execution of antisaccades in schizophrenia.

Adult↗

Genetic association of a cystatin C gene polymorphism with late-onset Alzheimer disease.

OBJECTIVE: To determine whether the cystatin C gene (CST3) is genetically associated with late-onset Alzheimer disease (AD). DESIGN: A case-control study with 2 independent study populations of patients with AD and age-matched, cognitively normal control subjects. SETTING: The Alzheimer's Disease Research Unit at the University Hospital Hamburg-Eppendorf, Hamburg, Germany, for the initial study (n = 260). For the independent multicenter study (n = 647), an international consortium that included the Massachusetts Alzheimer's Disease Research Center at the Massachusetts General Hospital, Boston; the Scientific Institute for Research and Patient Care, Brescia, Italy; and Alzheimer's research units at the Universities of Basel and Zurich, Switzerland, and Bonn, Goettingen, and Hamburg, Germany. PARTICIPANTS: Five hundred seventeen patients with AD and 390 control subjects. MEASURES: Molecular testing of the KspI polymorphisms in the 5' flanking region and exon 1 of CST3 and the apolipoprotein E (APOE) genotype. Mini-Mental State Examination scores for both patients with AD and control subjects. RESULTS: Homozygosity for haplotype B of CST3 was significantly associated with late-onset AD in both study populations, with an odds ratio of 3.8 (95% confidence interval, 1.56-9.25) in the combined data set; heterozygosity was not associated with an increased risk. The odds ratios for CST3 B/B increased from 2.6 in those younger than 75 years to 8.8 for those aged 75 years and older. The association of CST3 B/B with AD was independent of APOE epsilon4; both genotypes independently reduced disease-free survival. CONCLUSIONS: CST3 is a susceptibility gene for late-onset AD, especially in patients aged 75 years and older. To our knowledge, CST3 B is the first autosomal recessive risk allele in late-onset AD.

Age of Onset↗

Hepatic fascioliasis: report of two cases.

Two cases of hepatic fascioliasis with characteristic features in US examinations and CT scans are presented. In both modalities they show tunnel-like branching and clustered areas of low echogenicity/density, which reach subcapsular regions. These cases are presented to recall the imaging features in hepatic fascioliasis especially outside endemic regions. Not only CT but also US is able to detect these characteristic lesions, which may help to make the diagnosis of hepatic fascioliasis in patients with clinical symptoms suggestive of parasitic disease.

Acute Disease↗

Six basic dimensions of personality and a seventh factor of generalized dysfunctional personality: a diathesis system covering all personality disorders.

The five-factor model (FFM) of personality has recently been claimed to be comprehensive for all dimensionally conceived personality disorders (PDs). This assumption is refuted on the grounds of a principal component analysis conducted for three basic factor inventories (FFPI, NEO-FFI, Hamburg Personality Inventory), 22 explorative facet scales for normal personality and a questionnaire inventory (Inventory of Clinical Personality Accentuations) of 24 PD scales. Seven substantial orthogonal Varimax factors were found explaining 73% of the total variance. The five factors of the FFM were replicated. In addition, a new basic factor 'risk and competition seeking' (basic dimension 'risk', BD-R) emerged replicating findings of Andresen. The massive seventh factor was substantially loaded by all 24 PD scales and interpreted as 'general dysfunctional personality' (GDP). Most of the highly loaded scales describe varying forms of cognitive aberration. Together with GDP, the six-factor model now explains about 73% of all PD scales, thus, a virtually comprehensive descriptive diathesis system is achieved. Without GDP and BD-R, only 25% can be accounted for by the FFM. Five of the six normal dimensions will be loaded with positive and negative signs by some PDs. Neuroticism (BD-N) is still unique regarding its positive substantial correlations with almost all PD scales. BD-N is also the only normal factor which is correlated with GDP at about 0.50. A geometric model for the relationships between basic and clinical factors is presented.

Adult↗

The activation of phospholipase D by endothelin-1, angiotensin II, and platelet-derived growth factor in vascular smooth muscle A10 cells is mediated by small G proteins of the ADP-ribosylation factor family.

We show here that A10 cells express the phospholipase D (PLD) isoforms PLD1b and PLD2. The activation of PLD in these cells by angiotensin II (AngII), endothelin-1 (ET-1), and platelet-derived growth factor (PDGF) was found to be sensitive to inhibitors of the activation of ADP-ribosylation factor (ARF) but not to blockers of Rho protein function. PDGF, AngII, and ET-1 induced the binding of ARF proteins to cell membranes in a permeabilized cell assay. Cells permeabilized and depleted of ARF were no longer sensitive to stimulation with AngII, ET-1, or PDGF, but the addition of recombinant myristoylated human ARF1 restored agonist-dependent PLD activity. Expression of dominant negative ARF mutants blocked receptor-dependent activation of PLD. PLD activity was also potently stimulated by treatment with phorbol esters, but this activity was only partially inhibited by brefeldin A or by the overexpression of ARF dominant negative mutants. Transient expression of catalytically inactive mutants of PLD2, but not PLD1, inhibited significantly PDGF- and AngII-dependent PLD activity. We conclude: 1) the activation of PLD by cell surface receptors occurs primarily by an ARF-dependent mechanism in A10 cells, whereas the activation of PLD by protein kinase C-dependent pathways is only partially dependent on the regulation of ARF proteins; and 2) cell surface receptors, such as AngII and PDGF, signal primarily via PLD2 in A10 cells.

ADP Ribose Transferases↗

Topography of the auditory P300 in schizotypal personality.

BACKGROUND: Research with schizophrenic patients has demonstrated reduced amplitude of the P300b elicited with the auditory "oddball" paradigm, as well as reduced P300a amplitude following "novel" stimuli. The focus of the present study was the investigation of these components in a nonclinical sample of participants with high expressions of the schizotypal personality trait. METHODS: By use of an acoustic oddball task, including the presentation of novel stimuli, the event-related brain potentials of 14 participants with "low" and 13 participants with "high" scores on the German adaptation of the "Schizotypal Personality Questionnaire" were investigated. Current source density (CSD) curves and spline-interpolated CSD maps were generated. Peak amplitudes and latencies of the N100, P200, P300a, and P300b were determined for the CSD data. RESULTS: Results indicate no group differences with respect to N100, P200, and P300a amplitudes and latencies. By contrast, the P300b amplitude was significantly smaller in high- as compared to low-scoring participants. Left-temporal as compared to right-temporal P300b was significantly smaller in high- than in low-schizotypal participants. CONCLUSIONS: Confirming results of other researchers, this present study suggests that a reduced P300b amplitude and an altered P300b topography at temporal sites may be a trait-like "marker" of the schizophrenia spectrum.

Adult↗