PubMed Health⌕ Search

Biomedical subjects

Georg Juckel

Publications and source records attributed to Georg Juckel.

34 records · Page 2Linked to original sources
PubMed2005

The European Prediction of Psychosis Study (EPOS): integrating early recognition and intervention in Europe.

This paper provides the rationale and design of the European Prediction of Psychosis Study (EPOS), the first European prospective transnational field study of the prodrome and moderating risk/resilience factors of psychosis. As different health systems provide different structures of care, prevention programmes will only be successfully implemented and sustained system-wide, if they can be adapted to the system's special opportunities and needs. EPOS will provide a sound data base for a future evidence-based prevention of psychosis. Data on the recruitment of subjects and on the distribution of the four clinical criteria for an at-risk mental state for psychosis are given.

Journal Article↗
PubMed2004

Differential effects of reboxetine and citalopram on hand-motor function in patients suffering from major depression.

RATIONALE: Motor dysfunctions might be a more common side effect of serotonergic than noradrenergic antidepressants. However, the effects of antidepressants on motor function in depression have rarely been analyzed systematically. Computerized methods allow the objective registration of drug-induced motor dysfunction and were applied in this study. OBJECTIVES: To examine the effects of a selective noradrenaline re-uptake inhibitor (NARI) (reboxetine) and a selective serotonin re-uptake inhibitor (SSRI) (citalopram) on hand-motor function in patients with major depression. METHODS: Different types of hand movements (drawing of circles and handwriting probes) were recorded and analyzed in 16 acutely depressed inpatients receiving citalopram (30-60 mg/day) and 12 acutely depressed inpatients treated with reboxetine (4-8 mg/day), using a digitizing tablet for the analysis of movement dynamics. Both groups were comparable regarding mean age (42-43 years), gender, handedness (preponderance of right-handers) and the mean baseline HAMD score (about 27). Five kinematical parameters reflecting velocity, regularity and degree of automation of hand movements have been computed. RESULTS: Reboxetine had significantly more favorable effects on fine motor function (increased velocity of rapid hand movements) in depressed patients than citalopram. These differences became obvious when patients conducted more complex tasks and are not explained by differential antidepressant effects. CONCLUSIONS: Our findings are in line with the hypothesis that SSRI tend to have small, but more pronounced negative effects on motor function than NARI.

Acute Disease↗
PubMed2004

[Genetic and pharmacological effects on prefrontal cortical function in schizophrenia].

Brain imaging studies with PET, SPECT, functional magnetic resonance imaging, and spectroscopy provide evidence of prefrontal dysfunction in schizophrenia. Dysfunction of the prefrontal cortex is associated with cognitive impairment and negative symptoms. Combined multimodal imaging shows that a developmentally early disturbance of frontotemporal-limbic neuronal networks is associated with a disinhibition of subcortical dopaminergic neurotransmission. Current studies imply genetic factors in the regulation of dopaminergic neurotransmission and their effects on prefrontal cortex function. Some studies also indicate that atypical neuroleptics may at least partially improve frontal cortex function. We review the literature and discuss genotype and medication effects on frontal dysfunction in schizophrenia. Molecular brain imaging combines imaging techniques with the assessment of genotype effects and represents a powerful tool for the understanding of neuropsychiatric disorders.

Antipsychotic Agents↗
PubMed2004

Integration of fMRI and simultaneous EEG: towards a comprehensive understanding of localization and time-course of brain activity in target detection.

fMRI and EEG are complimentary methods for the analysis of brain activity since each method has its strength where the other one has limits: The spatial resolution is thus in the range of millimeters with fMRI and the time resolution is in the range of milliseconds with EEG. For a comprehensive understanding of brain activity in target detection, nine healthy subjects (age 24.2 +/- 2.9) were investigated with simultaneous EEG (27 electrodes) and fMRI using an auditory oddball paradigm. As a first step, event-related potentials, measured inside the scanner, have been compared with the potentials recorded in a directly preceding session in front of the scanner. Attenuated amplitudes were found inside the scanner for the earlier N1/P2 component but not for the late P300 component. Second, an independent analysis of the localizations of the fMRI activations and the current source density as revealed by low resolution electromagnetic tomography (LORETA) has been done. Concordant activations were found in most regions, including the temporoparietal junction (TPJ), the supplementary motor area (SMA)/anterior cingulate cortex (ACC), the insula, and the middle frontal gyrus, with a mean Euclidean distance of 16.0 +/- 6.6 mm between the BOLD centers of gravity and the LORETA-maxima. Finally, a time-course analysis based on the current source density maxima was done. It revealed different time-course patterns in the left and right hemisphere with earlier activations in frontal and parietal regions in the right hemisphere. The results suggest that the combination of EEG and fMRI permits an improved understanding of the spatiotemporal dynamics of brain activity.

Acoustic Stimulation↗
PubMed2004

Serotonin and dopamine transporter availabilities correlate with the loudness dependence of auditory evoked potentials in patients with obsessive-compulsive disorder.

Brain monoaminergic function is involved in the pathophysiology of psychiatric disorders. The loudness dependence (LD) of the N1/P2 component of auditory evoked potentials has been proposed as a noninvasive indicator of central serotonergic function, whereas single photon emission computed tomography (SPECT) and [123I]beta-CIT can be used to visualize both serotonin (SERT) and dopamine transporters (DAT). The aim of the study was to correlate LD and SPECT measures in patients with obsessive-compulsive disorder, a condition with evidence for a serotonergic dysfunction. A total of 10 subjects received both neurophysiological and imaging investigations. Evoked potentials were recorded following the application of acoustic stimuli with increasing intensities. The LD of the relevant subcomponents (tangential dipoles) was investigated using dipole source analysis. SPECT was performed 20-24 h after injection of a mean 140 MBq [123I]beta-CIT. As a measure of brain SERT and DAT availabilities, a ratio of specific to nonspecific [123I]beta-CIT binding for the midbrain . pons region (SERT) and the striatum (DAT) was used. The LD of the right tangential dipole correlated significantly with both SERT and DAT availabilities (Pearson's correlations: rho = 0.69, p < 0.05, and rho = 0.80, p < 0.01, respectively). The correlations remained significant after controlling for the effects of age, gender, and severity of clinical symptoms. Associations between LD and both SERT and DAT availabilities further validate the use of neurophysiological approaches as noninvasive indirect measures of neurochemical brain function and point at a hypothesized interconnection of central monoaminergic systems.

Acoustic Stimulation↗
PubMed2003

Elevated brain serotonin transporter availability in patients with obsessive-compulsive disorder.

BACKGROUND: A central serotonergic dysfunction is considered to be involved in the pathophysiology of obsessive-compulsive disorder (OCD). The aim of this study was to investigate the serotonin transporter availability in patients with OCD as an in vivo marker of the central serotonergic system. METHODS: Nine unmedicated (7 drug-naive) patients with OCD and 10 healthy control subjects were included and received single photon emission computed tomography (SPECT) 20.75 +/- 1.51 hours after injection of a mean 147.20 +/- 6.74 MBq [(123)I]-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane ([(123)I]beta-CIT). As a measure of brain serotonin transporter availability, a ratio of specific-to-nonspecific [(123)I]beta-CIT binding for the midbrain-pons (V(3)" = [midbrain/pons-occipital]/occipital) was used. RESULTS: Mean specific-to-nonspecific ratios showed a 25% higher midbrain-pons [(123)I]beta-CIT binding in the patients as compared with healthy controls (2.26 +/-.37 vs. 1.81 +/-.23, p <.01). The difference remained significant after adjustment for clinical variables and controlling for age and gender. Stratification of the patients according to onset of the disorder revealed significant differences between controls and patients with early (childhood, adolescence) but not late (adult) onset of OCD. CONCLUSIONS: The study provides evidence of a serotonergic dysfunction in patients with OCD and suggests a serotonergic component in the pathophysiology of the disorder.

Adult↗
PubMed2003

Serotonergic dysfunction in schizophrenia assessed by the loudness dependence measure of primary auditory cortex evoked activity.

Increased serotonergic activity is discussed as an important pathogenetic factor in schizophrenia. Further support for this hypothesis is difficult to obtain due to the lack of valid indicators of the brain's serotonin system. A great deal of evidence discovered through human and animal studies suggests that a weak loudness dependence of auditory evoked potentials (LDAEP) indicates high serotonergic activity and vice versa. The LDAEP is a measure of auditory cortex activity, reflecting increase or decrease of auditory evoked potential amplitudes with increasing tone loudness, which is probably modulated by the serotonergic innervation there. This is true only for the LDAEP of the primary auditory cortex, since this region is more highly innervated by serotonergic fibers than the secondary auditory cortex. The LDAEP (N1/P2 component) of 25 inpatients with schizophrenia free of medication and 25 healthy controls matched by age and gender, were recorded. Using dipole source analysis, the LDAEP of primary (tangential dipole) and this of secondary auditory cortex (radial dipole) was separately analyzed. Following a 4-week treatment with the 5-HT(2) antagonists clozapine or olanzapine, patients were once again studied. The LDAEP of the primary, but not of the secondary auditory cortex, was significantly weaker in the patients with schizophrenia than in healthy volunteers, indicating enhanced serotonergic neurotransmission. After treatment with the 5-HT(2) antagonists, the LDAEP (of the right hemisphere) tended to be increased, indicating normalization of serotonergic function in the patients with schizophrenia. These results suggest that the loudness dependence of primary auditory cortex evoked activity is well suitable to assess serotonergic dysfunction in schizophrenia.

Adult↗
PubMed2003

Effects of sertraline on kinematic aspects of hand movements in patients with obsessive-compulsive disorder.

RATIONALE: Movement disorders such as disturbances of fine motor co-ordination are a frequent phenomenon in patients with obsessive-compulsive disorder (OCD). OBJECTIVES: Our aim was to investigate changes of hand-motor dysfunction in OCD patients under the influence of 10-week treatment with sertraline and behaviour therapy. METHODS: We examined the performance of 40 patients satisfying DSM-IV criteria for OCD before and under this therapy using a digitising tablet and kinematic analysis of handwriting and drawing movements. Forty healthy controls were also tested (test-retest interval: 10 weeks). RESULTS: The speed of drawing was significantly lower in OCD patients than in controls (mean+/-standard deviation=197.03+/-113.26 mm/s for patients and 182.48+/-189.61 mm/s for controls; P=0.01). After 10 weeks of therapy, this parameter normalised in patients (from 197.03+/-113.26 mm/s to 163.66+/-101.92 mm/s; P=0.001). CONCLUSIONS: Hand-motor dysfunction (especially bradykinesia) improves with a serotonin-enhancing therapy in OCD patients.

Adult↗
PubMed2003

EEG abnormalities associated with antipsychotics: a comparison of quetiapine, olanzapine, haloperidol and healthy subjects.

In this study the effects of the atypical antipsychotics quetiapine and olanzapine, and the typical antipsychotic haloperidol on EEG patterns were retrospectively investigated in 81 patients under stable monotherapy with either drug (quetiapine: n=22, olanzapine: n=37, haloperidol: n=22). These three subgroups were compared with a control group of healthy subjects (n=30) which were matched regarding sex and age. Diagnoses of patients were schizophrenia (DSM-IV 295.xx, n=61), brief psychotic disorder (DSM-IV 298.8, n=9), schizoaffective disorder (DSM-IV 295.70, n=8) and delusional disorder (DSM-IV 297.1, n=3). There were no statistically significant differences regarding demographic characteristics between the groups. Digital EEG recordings were retrieved from a database and visually assessed by two independent investigators, and one blinded regarding medication. One patient from the quetiapine group (5%), 13 olanzapine patients (35%), five of the haloperidol patients (23%) and two subjects of the control group (7%) had an abnormal EEG. Epileptiform activity was observed in four patients (11%) of the olanzapine group, and none in the others. EEG abnormalities were statistically significantly increased with dose in the olanzapine group, in contrast to patients treated with haloperidol, quetiapine or healthy subjects. In conclusion, EEG abnormalities seem to occur rarely in patients treated with quetiapine comparable to the control group, but significantly more often with haloperidol and olanzapine, possibly due to different receptor profiles of these substances. To our knowledge, this is the first electrophysiological investigation comparing the new atypical antipsychotics quetiapine, haloperidol, olanzapine with healthy subjects.

Adolescent↗
PubMed2002

Allelic variants of the functional promoter polymorphism of the human serotonin transporter gene is associated with auditory cortical stimulus processing.

The loudness dependence (LD) of the auditory-evoked N1/P2 component has been shown to be related to the central serotonergic neurotransmission. Allelic variants in the promoter region of the 5-hydroxytryptamine transporter (5-HTT) gene were shown to modulate serotonergic activity. It was hypothesized that the three genotypes (l/l, s/l, s/s) differ with respect to LD. Allelic variants of the 5-HTT promoter region and LD at the Cz electrode were determined in 185 healthy subjects prospectively. A significant association was found between LD and genotype (ANOVA: F=4.172, p=0.017). Individuals homozygous for the l allele exhibited a weaker LD compared to heterozygous subjects. The results are consistent with the reported association between 5-HTT genotype and serotonin transport capacity in lymphoblasts, and indicate that auditory stimulus processing is associated with genetic variants of the brain serotonergic system. The LD may serve as endophenotype in human serotonin research.

Adult↗
PubMed2002

P300 subcomponents and clinical symptoms in schizophrenia.

A small P300 component of the auditory event-related potential has been found to predict poor clinical outcome with a higher amount of thought disorders in schizophrenia and has been proposed as a marker for an underlying neurodevelopmental disorder with prominent thought disorders, early age of onset, prominent negative symptoms and positive family history. The present study was designed to confirm our previous findings with subcomponent analysis. Using dipole source analysis a temporo-basal (TB) P300 as well as a temporo-superior (TS) P300 and LP potential were separated. Fifty patients with schizophrenia (DSM-IV) were included in the study. Late auditory event-related P300 potentials were recorded to infrequent auditory stimuli after treatment psychopathology and family history were assessed. The TB-P300 amplitudes were significantly negatively correlated with thought disorders remaining after treatment and were positively correlated with age of onset. Illness duration was significantly correlated to TB-P300 and TS-P300 amplitudes in the group of patients with late onset. No significant correlations were found with negative symptoms. Family history did not show significant effects on P300. A smaller P300 in patients with more thought disorder remaining after stabilization on medication and an earlier age of onset support the hypothesis that P300 characterizes schizophrenic patients with an underlying neurodevelopmental disorder with specific clinical symptom clusters. On the other hand, diminished P300 with illness duration in the group of patients with later age of onset supports an underlying neurodegenerative progressive process in this subgroup of patients.

Adolescent↗
PubMed2002

Identification of a naturally occurring polymorphism in the promoter region of the norepinephrine transporter and analysis in major depression.

Disturbances in the noradrenergic neurotransmission system have been implicated in the etiology of mood disorders. The norepinephrine transporter (NET) is a main target of antidepressant action and was shown to be dysregulated in major depression. Despite the clinical and physiological significance of NET gene regulation, little is known about the transcriptional control mechanisms governing its expression. Since it is well established that affective disorders have a genetic component with many genes of small effect contributing to the genetic susceptibility of depression, the NET gene is an interesting candidate gene for affective disorders. In a search for polymorphisms or mutations in the 5' flanging region of the NET gene we sequenced approximately 1000 bp upstream of the first codon in the NET gene promoter in 100 patients with major depression and 100 healthy controls. We identified a so far unknown T --> C polymorphism 182 bp upstream of the start codon in a transcriptional relevant region. In a case control association study we investigated the newly identified T-182C polymorphism and an already known G1287A polymorphism in exon 9 of the NET gene in a sample of 193 patients with major depression and 136 healthy, non-related controls. No statistical significant differences between patients and controls were found for any of the analyzed polymorphisms, either in the genotype distribution or in the allele frequencies. Our results suggest that the investigated polymorphisms are not major susceptibility factors in the etiology of major depression.

Adult↗
PubMed2002

Value of event-related P300 subcomponents in the clinical diagnosis of mild cognitive impairment and Alzheimer's Disease.

Accurate and early diagnosis of Alzheimer's Disease (AD) with reliable and noninvasive methods is of great importance for clinical practice as effective and specific antidementive therapies become available. The aim of the study was to evaluate the clinical relevance of event-related P300 in the early diagnosis of AD. Thirty patients with AD, 26 patients with mild cognitive impairment (MCI) from our Memory Clinic and 26 age-matched healthy controls (HC) were studied with event-related P300 potentials. Amplitudes of temporo-basal dipoles (TB-P300) were significantly diminished in AD compared to HC and MCI. Furthermore, latencies of temporo-superior dipoles (TS-P300) were significantly prolonged in AD compared with HC. Sensitivity was 90.0% for the differentiation of patients with AD from HC (specificity 79.1%) using reduced TB-P300 amplitudes and prolonged TS-P300 latencies. Similar results were found using Pz amplitudes as well as Fz latencies. Our data suggest that TB-P300 amplitudes and TS-P300 latencies may be an accurate clinically available, nonexpensive, noninvasive, and reliable marker for AD.

Aged↗
PubMedDate not supplied

P300 subcomponents in obsessive-compulsive disorder.

Hyperactivity in the frontal cortex, leading to acceleration of attentional and cognitive processes, is discussed as pathogenetic factor in obsessive-compulsive disorder (OCD), as supported by findings of neuroimaging studies. This dysfunction in patients with OCD could be reflected by the auditory event-related P300 component, since one subcomponent of the P300, the so-called P3a, is mainly generated in frontal regions. The P300 of 21 patients with OCD free of medication and 21 age- and sex-matched healthy controls was studied, and dipole source analysis was used, allowing the separation of the subcomponents P3a and P3b with high reliability. No difference concerning the P3a between OCD and healthy subjects was found. OCD patients, however, showed a larger P3b amplitude and a shorter P3b latency (only right hemisphere) as well as a shorter reaction time to target tones as the healthy controls. Since the P3b, generated mainly in the temporo-parietal junction, is related to attentional and higher cognitive functions, whereas the P3a is more related to unspecific orienting reactions, the P3b abnormalities found in these patients could be an electrophysiological correlate of overfocussed attention and faster cognitive processes in OCD, possibly due to higher arousal and noradrenergic function. Regarding the findings with small P300 amplitudes and long latencies in most of the other psychiatric patients, it is remarkable that OCD is one of the few psychiatric diseases being characterized by larger P3b amplitudes and shorter latencies.

Adult↗