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Biomedical subjects

Georg Juckel

Publications and source records attributed to Georg Juckel.

At least 19 recordsLinked to original sources

Effects of quetiapine on cognitive functioning in schizophrenia: evidence for the remyelination hypothesis?

Postmortem findings, neuroimaging data, and in-vitro models suggest a decrease in number and density of oligodendrocytes is driving cognitive deficits in schizophrenia (SCZ). Second-generation antipsychotics are discussed to improve oligodendrocyte dysfunction with most conclusive evidence available for quetiapine (QET). We postulate that sustained QET treatment leads to cognitive improvement in SCZ, particularly, in tests with high demands for working memory function. We further hypothesize that these effects are moderated by polygenic factors associated with hippocampus-related brain volumes, general white matter integrity, and/or oligodendroglia-related SCZ risk. Using data of the prospective PsyCourse study, we identified 166 patients with SCZ spectrum disorder receiving QET at one or two consecutive visits plus 166 matched patients without QET. Polygenic scores were calculated for subcortical brain volumes, measures of white matter integrity, and for cell type-specific genetic SCZ risks. QET treatment was consistently associated with improved cognitive function independent of time, specifically, in tests with high, but not with low to medium working memory load. Polygenic analyses did not reveal significant moderation effects. In contrary, low genetic SCZ risk specific for genes related to human oligodendrocyte function was associated with higher cognitive performance independent from QET. While we observed improved cognitive performance under QET in high working memory tests, we did not find evidence that polygenic factors associated with hippocampus-related brain volumes, white matter integrity, or oligodendroglia-related SCZ risk moderate this association. Thus, our tentative findings do not provide evidence for the hypothesis that polygenic estimates of hippocampal remyelination capacities influence the association between QET and cognitive performance in SCZ.

Humans↗

Facial expressions and personality: a kinematical investigation during an emotion induction experiment.

BACKGROUND/AIMS: In order to elucidate the relationship between personality traits and expression of positive emotions in healthy volunteers, standardized personality inventories and kinematical analysis of facial expressions can be helpful and were applied in the present study. METHODS: Markers fixed at distinct points of the face emitting ultrasonic signals at high frequency gave a direct measure of facial movements with high spatial-temporal resolution. Forty-six healthy participants (mean age: 40.7 years; 20 males, 26 females) watching a witty movie ("Mr. Bean") were investigated. RESULTS: Speed of "laughing" was associated with higher scores on Zuckerman's Sensation Seeking Scale and NEO-FFI (Openness to Experience). CONCLUSION: Kinematical analysis of facial expressions seems to reflect sensation seeking and related personality styles. Higher speed of facial movements in sensation seekers suggests lowered serotonergic function.

Adult↗

Quetiapine indication shift in the elderly: diagnosis and dosage in 208 psychogeriatric patients from 2000 to 2006.

RATIONALE: Quetiapine was approved in Germany as an atypical antipsychotic for treatment of schizophrenia in 2000, followed by the approval as an antipsychotic for treatment of bipolar mania in 2003. The approval of quetiapine for treatment of bipolar depression is expected. We hypothesized that the psychogeriatric prescription pattern for quetiapine shifts from the psychotic to the affective spectrum. METHODS: Retrospectively we screened discharge reports of all geriatric inpatients of the psychiatric department of the Ruhr-University of Bochum in the period from January 2001 until March 2006 and identified 208 individual patients aged over 60 years, who had received quetiapine as final medication. Age, gender, daily drug dose, year of treatment and diagnosis (according to ICD-10) were recorded and analyzed. RESULTS: Over the six-year time span, the proportion of affective disorders (F3) as indication for quetiapine in the elderly increased, whereas the proportion of dementia (F0) as indication for quetiapine decreased significantly. The proportion of schizophrenic disorders (F2) treated with quetiapine did not change significantly. DISCUSSION: Since the decision of the German Federal Court in 2002 'off label' use goes to the expenses of the prescriber. So the decrease of quetiapine in dementia is probably due to its 'off label' status in dementia. The psychogeriatric indication shift for quetiapine towards affective disorders could be the consequence of good clinical experiences with the drug and growing evidence for its antidepressant effect. CONCLUSION: In addition to controlled pharmacological trials prospective clinical research is needed to evaluate the prescription attitudes of clinicians.

Aged↗

Early recognition of bipolar disorder.

Bipolar disorders are frequently not diagnosed until long after their onset, leaving patients with no or correspondingly inadequate treatment. The course of the disorder is all the more severe and the negative repercussions for those affected all the greater. Concerted research effort is therefore going into learning how to recognize bipolar disorders at an early stage. Drawing on current research results, this paper presents considerations for an integrative Early Symptom Scale with which persons at risk can be identified and timely intervention initiated. This will require prospective studies to determine the predictive power of the risk factors integrated into the scale.

Adolescent↗

Prediction of treatment response in major depression: integration of concepts.

BACKGROUND: Two promising approaches have been introduced for the prediction of treatment response in major depression: one concept is based on the activity in the rostral anterior cingulate cortex (rACC). Subjects with higher metabolic rates respond better to sleep deprivation or antidepressive medication. Another approach is the investigation of the loudness dependence of the auditory evoked potential (LDAEP). Here, a high LDAEP is supposed to reflect low central serotonergic activity. We present the first study comparing both approaches in the same group of patients. METHODS: Patients with major depression (n=20) were investigated using both resting EEG and LDAEP before treatment with either citalopram or reboxetine. RESULTS: We found significant differences between responders and non-responders in the rACC in the theta-frequency range (6.5-8 Hz, p<0.05). In the subgroup of patients, treated with citalopram we found higher LDAEP-values in responders versus non-responders (p<0.05) and a significant correlation between pre-treatment-LDAEP and improvement in the Hamilton score after treatment (r=0.71, p<0.05). CONCLUSIONS: In combining both methods a prediction whether a patient with major depression might be at risk for non-response to a standard therapy as well as a suggestion for a pharmacological approach of choice seems to be possible.

Antidepressive Agents↗

Dysfunction of ventral striatal reward prediction in schizophrenic patients treated with typical, not atypical, neuroleptics.

RATIONALE: Clinical studies in patients with schizophrenia suggest that atypical neuroleptics are more effective than typical neuroleptics in reducing negative symptoms including apathy and anhedonia. Dysfunction of the dopaminergic reward system may contribute to negative symptoms in schizophrenia. OBJECTIVE: We used functional magnetic resonance imaging to assess the blood oxygen level dependency response in the ventral striatum of medicated schizophrenics and healthy control subjects during reward anticipation. METHODS: Twenty schizophrenics [ten medicated with typical (e.g., haloperidol) and ten with atypical (e.g., olanzapine and risperidone) neuroleptics] and ten age-matched healthy volunteers participated in an incentive monetary delay task in which visual cues predicted that a rapid response to a subsequent target stimulus would result either in monetary gain or no consequence. RESULTS: Healthy volunteers and schizophrenics treated with atypical neuroleptics showed ventral striatal activation in response to reward-indicating cues, but schizophrenics treated with typical neuroleptics did not. In patients treated with typical neuroleptics, decrease in activation of the left ventral striatum was correlated with the severity of negative symptoms. CONCLUSIONS: Failure to activate the ventral striatum during reward anticipation was previously associated with the severity of negative symptoms in schizophrenia and was also found in schizophrenics treated with typical neuroleptics in this study. Significant blunting of ventral striatal activation was not observed in patients treated with atypical neuroleptics, which may reflect the improved efficacy of these drugs in treating negative symptoms.

Adult↗

Symptom-specific EEG power correlations in patients with obsessive-compulsive disorder.

Neurophysiological studies in patients with obsessive-compulsive disorder (OCD) consistently revealed frontal alterations of cortical activity but otherwise showed inhomogeneous results, conceivably due to variable subgroups with diverse pathomechanisms involved. The aim of this study was to investigate quantitative electroencephalography (EEG) in patients with OCD as compared to healthy controls and to correlate neurophysiological data with clinical variables. EEGs were digitally recorded from 18 unmedicated patients (8 male, mean age 32.4+/-11.8 years, Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) 15.3+/-7.9) and 18 matched healthy controls, and analysed quantitatively. The mean frequency of EEG background activity and absolute power in delta, theta, alpha and beta frequency bands were calculated. Mean frequency of background activity was significantly lower in patients as compared to controls (-1.44/s, p<0.01), predominantly for the frontal electrode positions. Power spectra revealed increased delta- and decreased alpha-/beta-power in the group of patients (p<0.05, patients vs. controls). Correlation analyses showed significant positive correlations of EEG-power with the Y-BOCS sub-scores "obsessions", and negative correlations with the sub-scores "compulsions" (Spearman's correlations, r(s)=+0.48 to +0.70, and -0.47 to -0.6, respectively, p<0.05). The data provide evidence of a dysfunction of frontal cortical activity in patients with OCD. The opposite correlations of neurophysiological data and clinical features, i.e. obsessions and compulsions, are suggestive of pathophysiological differences based on the presence of the respective cardinal symptoms of OCD.

Adolescent↗

Is the loudness dependence of auditory evoked potentials modulated by the selective serotonin reuptake inhibitor citalopram in healthy subjects?

The loudness dependence of auditory evoked potentials (LDAEP) has been discussed as a non-invasive in vivo marker of central serotonergic function. Evidence for this has been found in animal studies, but studies in humans provide less consistent results. In this study, the relationship between LDAEP and directly modulated central serotonergic activity in healthy subjects was investigated. In a single-blind cross-over design, the LDAEP of female participants (age: 24.0 +/- 2.3 years) was measured under two conditions: (1) infusion of 20 mg citalopram diluted in 250 ml 0.9% saline and (2) infusion of 250 ml 0.9% saline as placebo. LDAEP was measured at five different time points before, during and up to 60 min after drug/placebo administration and dipole source analysis was performed. The increase of the central serotonin activity in response to citalopram was not accompanied by a significant change of the LDAEP compared to the placebo condition. The result underlines that the acceptance of LDAEP as a marker of central serotonergic function still needs further discussion.

Acoustic Stimulation↗

A Ser9Gly polymorphism in the dopamine D3 receptor gene (DRD3) and event-related P300 potentials.

An important reason for the interest in P300 event-related potentials are findings in patients with psychiatric disorders like schizophrenia or alcoholism in which attenuations of the P300 amplitude are common findings. The P300 wave has been suggested to be a promising endophenotype for genetic research since attenuations of the amplitude and latency can be observed not only in patients but also in relatives. In parallel, the search for genes involved in the pathogenesis of psychiatric disorders has revealed for both, schizophrenia and alcoholism an association with a DRD3 Ser9Gly polymorphism in a number of studies. In the present study, we have investigated 124 unrelated healthy subjects of German descent and have found diminished parietal and increased frontal P300 amplitudes in Gly9 homozygotes in comparison to Ser9 carriers. This finding suggests a possible role of the DRD3 receptor gene in the interindividual variation of P300 amplitudes. Further studies should address the direct role of the DRD3 Ser9Gly polymorphism in attenuated P300 amplitudes in psychiatric disorders like schizophrenia or alcoholism.

Acoustic Stimulation↗

An integrative model of developing tinnitus based on recent neurobiological findings.

Brain imaging studies suggest that the functional connectivity of various limbic, prefrontal, and temporal brain structures can be understood as the basis for particularly intense experiences of impairment and many secondary symptoms of decompensated tinnitus. Results to date suggest cortical plasticity as a likely mechanism to be involved in the chronic progression of tinnitus. Relationships between the processing of auditory signals and neural networks associated with somatosensory, attentional, cognitive and emotional processes are relevant for the genesis of the pathology. However, the neural bases of subjective impairment in tinnitus patients are unknown. An integrative model of developing tinnitus is presented here, based on the most recent neurophysiological data in current discussion. We assume the involvement of altered brain functions in the development and maintenance of perceptions of tinnitus and outline various possibilities which could contribute to decompensation and chronic progression. The discussions surrounding present models of the generation of tinnitus and its reinforcement to the point of decompensation make it clear that a unidimensional approach in clinical interventions is insufficient. Patients with decompensated tinnitus suffer from a complex somatic and psychological disorder. The interactive processes involving emotions, behaviour and symptoms, as well as the high co-morbidity with affective and psychosomatic illnesses and the important influence of psychosocial factors (distress), make the use of stage-appropriate interdisciplinary treatments necessary.

Brain↗

Dysfunction of ventral striatal reward prediction in schizophrenia.

BACKGROUND: Negative symptoms may be associated with dysfunction of the brain reward system in schizophrenia. We used functional magnetic resonance imaging (fMRI) to assess the BOLD response in the ventral striatum of unmedicated schizophrenics during presentation of reward-indicating and loss-indicating stimuli. METHODS: A total of 10 schizophrenic men (7 never medicated, 3 unmedicated for at least 2 years) and 10 age-matched healthy male volunteers participated in an incentive monetary delay task, in which visual cues predicted that a rapid response to a subsequent target stimulus would result either in monetary gain or loss or would have no consequence. RESULTS: Compared to healthy controls, unmedicated schizophrenics showed reduced ventral striatal activation during the presentation of reward-indicating cues. Decreased activation of the left ventral striatum was inversely correlated with the severity of negative (and trendwise positive) symptoms. DISCUSSION: Reduced activation in one of the central areas of the brain reward system, the ventral striatum, was correlated with the severity of negative symptoms in medication-free schizophrenics. In unmedicated schizophrenic patients, a high striatal dopamine turnover may increase the "noise" in the reward system, thus interfering with the neuronal processing of reward-predicting cues by phasic dopamine release. This, in turn, may contribute to negative symptoms as such as anhedonia, apathy, and loss of drive and motivation.

Adult↗

Sound level dependence of the primary auditory cortex: Simultaneous measurement with 61-channel EEG and fMRI.

Sound level dependence has been investigated for years with event-related potentials (ERP). A serotonergic modulation of the sound level dependence only of the primary auditory cortex but not of the auditory association cortex has been suggested by a number of clinical and preclinical studies. Therefore, a precise covering of the activity of the primary auditory cortex seems necessary if sound level dependence is used as an indicator of the central serotonergic system. Recent fMRI studies described a pronounced sound level dependence only in the Heschl gyrus/primary auditory cortex but not in auditory association areas. In the present simultaneous 61-channel EEG and fMRI study investigating fourteen healthy subjects, we found a high correlation between the loudness-dependent change of the extent of fMRI activation (number of activated voxels) and the corresponding changes of the mean current source density within the same region of interest covering the primary auditory cortex (r = 0.84, P < 0.001). Our findings suggest a close relationship between the fMRI signal and event-related potential activity. In addition, the correspondence of the ERP-based data and the fMRI results further supports the validity of the ERP localization approach.

Acoustic Stimulation↗

Anxious and hyperactive phenotype following brief ischemic episodes in mice.

BACKGROUND: Poststroke emotional and behavioral abnormalities have an impact on outcome but have scarcely been characterized in animal models. We tested whether brief ischemic episodes induce behavioral changes in mice. METHODS: 129/Sv mice were subjected to 30-min occlusion of left or right middle cerebral artery (MCAo) followed by reperfusion or sham operation (n = 9 or 10 per group). Eight to ten weeks later, mice were tested for spontaneous locomotor activity, anxiety in the elevated plus maze, and depressive behavior in the modified Porsolt forced swim test. Outcome was correlated to monoamine and amino acid levels and compared with histologic damage at 10 weeks. RESULTS: Ischemia was associated with increased activity (right MCAo) and anxiety (left MCAo), but not poststroke depression. Noradrenaline increased by 30%-45% in the ischemic striatum and correlated with locomotor activity (r = .48); dopamine and homovanillinic acid were decreased compared with sham. The lesion was confined to the striatum, and scattered neuronal death was observed in a number of remote brain regions. CONCLUSION: Brief ischemic episodes in the mouse induce an anxious, hyperactive but not depressive phenotype that may relate to left versus right hemispheric lesion location, alterations in brain monoamine levels, and selective neurodegeneration.

Animals↗

Can a subgroup of OCD patients with motor abnormalities and poor therapeutic response be identified?

RATIONALE: In a subgroup of patients with obsessive-compulsive disorder (OCD), motor soft signs, tics and other movement disorders can be observed, indicating a special pathogenetic involvement of basal ganglia. OBJECTIVES: The main objective of this study was to verify the hypothesis that such motor dysfunction characterises a subgroup of OCD patients with poor treatment response. For assessing even subtle motor dysfunction, a new method for kinematical analysis of hand movements has been applied. METHODS: We examined the performance of 45 in-patients who met the DSM-IV criteria for OCD before and under therapy (sertraline and behaviour therapy) using a digitising tablet and kinematical analysis of simple handwriting and drawing movements. All subjects wrote a sentence, their signature and letter sequences. Moreover, they drew circles under different conditions. Three kinematical parameters (stroke duration, variation coefficient of peak velocity, stroke length) were calculated to quantify hand-motor performance. RESULTS: Prior to therapy, non-responders wrote with significantly smaller amplitudes than responders. Additionally, non-responders drew significantly larger circles with the non-dominant hand at baseline, as compared to responders. Disturbances of handwriting were more frequent in non-responders than in responders. CONCLUSIONS: Kinematical analysis of handwriting movements seems to be interesting for the prediction of poor response to treatments in OCD patients.

Adult↗

[Kinematic movement analyses and their application in psychiatry].

There is a long tradition to develop valid instruments for the exact assessment of psycho-motor dysfunctions in psychiatry. However, progress is hampered by the complexity of emotionally driven movements in psychiatric patients. Methods used up to now either remains unspecific due to only qualitative measurements or focus on the neurophysiological aspects too much. Thus, the results accomplished so far are only very general unspecific concerning different groups of psychiatric patients. In this paper, two own methods are presented which are aimed to avoid the two poles above mentioned. Kinematic analyses of facial expressions as well as handwriting movements provide quantitative and quite specific informations about psycho-motor dysfunctions of psychiatric patients and the effects of psychotropic substances. Thus, these methods are well suitable for relating them to other neurobiological parameters in order to contribute to the pathophysiological understanding of psycho-motor symptoms in psychiatric patients.

Antipsychotic Agents↗