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Biomedical subjects

H J Möller

Publications and source records attributed to H J Möller.

At least 19 recordsLinked to original sources
PubMed2006

Effects of treatment with the atypical neuroleptic quetiapine on working memory function: a functional MRI follow-up investigation.

BACKGROUND: Working memory as a part of higher-order executive functions is defined by the parallel storage and processing of information. Recent functional fMRI studies have revealed a functional, interregional disintegration of a neuronal network connecting cortical, subcortical and cerebellar regions in schizophrenic patients (SZ). Cognitive impairment in working memory is a core psychopathological correlate of schizophrenic symptoms. Atypical neuroleptics such as quetiapine have shown good efficacy in treating positive and negative symptoms. The presented study evaluated the impact of a neuroleptic steady state treatment with quetiapine on the altered working memory activation patterns in schizophrenia. METHODS: Patients were examined by fMRI at baseline and after 12 weeks of steady state treatment with quetiapine. Matched healthy controls (HC) underwent baseline examination. In the scanner, stimuli were presented in a 2-back and 0-back condition of a working memory (wm) paradigm, whereby a degraded and a non-degraded version were used each time. Additionally, behavioural responses (reaction time to target stimuli and error ratio) were measured. RESULTS: At baseline, healthy controls revealed increased activity in the frontal lobe, especially in regions of the prefrontal cortex. Compared to HC, SZ showed hypoactivation in the right dorsolateral prefrontal cortex (DLPFC) and the ventrolateral prefrontal cortex (VLPFC) bilaterally for the 2-back condition. In the 2-back degraded condition there was a hypoactivation in both, the right DLPFC and the VLPFC. Additionally, patients showed bilaterally decreased activation in the basalganglia in the 2-back and in the right caudatus in the 2-back degraded condition compared to healthy controls. After treatment with quetiapine, patients activations patterns were increased. The pre-post comparison of the 2-back condition revealed a significant increase of activation in the left VLPFC at a significance level of 0.001 (uncorrected). The 2-back degraded condition led to a significant activation pattern in the lingual gyrus and the right precuneus. In both wm conditions, at baseline there were no differences in reaction time but only a worse performance in SZ. After treatment, behavioural measurement of responses, including reaction time and performance, showed slight improvements in SZ, although these did not reach statistical significance. CONCLUSIONS: The neuronal networks underlying working memory are clearly altered in schizophrenia. After 12 weeks of treatment with quetiapine monotherapy, patients showed significant clinical improvement and revealed increased BOLD activity in the VLPFC during a working memory task, although there was no improvement of cognitive performance.

Adult↗
PubMed2005

[Diagnostics and therapy of depressive symptoms in schizophrenic patients].

The occurrence of depressive symptoms in schizophrenia is fairly common. In contrast to earlier assumptions, they usually have unfavorable consequences on the course of the disease. The response of depressive symptoms to therapy is well documented by empirical evidence and studies. In reality, however, the treatment of depressive symptoms in cases of schizophrenia occurs too rarely. This lack of medical treatment is partially explained by the clinicians' apprehension that antidepressive therapy could provoke a flare up of the psychosis. Nonetheless, this situation is often founded on the incorrect assessment of the depressive symptoms as negative symptoms that, in turn, are regarded by many clinicians as having limited treatability. In regards to this circumstance, a rethinking is desirable and, as a matter of principle, necessary.

Antidepressive Agents↗
PubMed2005

[Modern therapy for dementia].

The most frequently diagnosed dementia diseases include Alzheimer disease (AD), vascular dementia (VD) and dementia with Lewy bodies. Cholinesterase (ChE) inhibitors and the NMDA receptor antagonist memantine are currently recommended as first line drugs for the treatment of AD. These anti-dementia drugs have not yet been approved for the treatment of VD and DLB although the results of controlled clinical studies support the effectiveness of the ChE inhibitors for both diseases. The treatment of the primary disease and the secondary prevention of cerebrovascular accidents constitute the primary objectives of VD therapy. Although single or multiple domain cognitive deficits are the clinical key symptoms of dementia, noncognitive psychopathological symptoms (so-called behavioral disorders) are particularly common and may even dominate the clinical course in the moderate to severe stages. Therefore, it is important to recognize, diagnose and specifically treat these additional symptoms. During the last decade, the classic neuroleptics and benzodiazepine have been largely replaced by modern antidepressants, atypical antipsychotics and benzodiazepine analogues.

Aged↗
PubMed2005

Hypermetabolic pattern in frontal cortex and other brain regions in unmedicated schizophrenia patients. Results from a FDG-PET study.

We report results of a FDG-PET study in 10 patients with schizophrenia (6 unmedicated, 4 never medicated) and 12 healthy age-matched controls. The patients met ICD-10 and DSM-IV criteria for schizophrenia and all reported psychotic, "positive" symptoms when tested. Schizophrenic patients had higher absolute CMRGlu values in almost all quantified regions compared to normal subjects. Using the occipital cortex as the reference region patients showed a hyperfrontal metabolic pattern. Other significant regional differences were found with respect to thalamus, striatum and temporal cortex. The finding of a hyperfrontality in un- and never medicated psychotic schizophrenic patients must be discussed in the light of the psychopathological symptoms of patients when tested, a possible disruption of cortico-striato-thalamic feedback loops and recent findings of a hyperfrontality in experimentally induced psychosis (ketamine- and psilocybin-model of schizophrenia).

Adult↗
PubMed2005

Thalamic volume in first-episode and chronic schizophrenic subjects: a volumetric MRI study.

OBJECTIVE: The thalamus, as a composite of several functionally very different nuclei, is a major relay and filter station in the CNS and is significantly involved in information processing and gating. The aim of our study is to investigate first-episode and chronic patients and controls to shed light on the potential pathogenetic role of the thalamus in schizophrenia and to assess the relationship between thalamic volumes and psychopathology ratings. METHODS: Forty-three male right-handed chronic and 25 male right-handed first-episode schizophrenic patients treated at the psychiatric hospital of the Ludwig-Maximilians University in Munich and 50 male control subjects were enrolled into the study. Demographic information and current symptom profile of all schizophrenic subjects were assessed using a semistructured interview, including a variety of measures relevant to the study. Volumetry of the thalamic gray and white matter was obtained with 1.5 T MRI, using the BRAINS software application. RESULTS: No significant differences regarding thalamic volumes were detected across groups. However, negative symptoms were significantly correlated with thalamic volumes in first-episode patients, whereas duration of illness and extrapyramidal symptoms were related to thalamic volumes in chronic patients. SUMMARY: Our findings indicate that, while the thalamus might be involved in the pathogenesis of negative symptoms, thalamic volume reduction is not a required element in the pathophysiology of the schizophrenic phenotype.

Adult↗
PubMed2005

[Selective serotonin and noradrenaline reuptake inhibitors: a step forward in the treatment of depression?].

With the tricyclics, selective serotonin reuptake inhibitors (SSRIs) and other substances, we now have available a range of medications for the treatment of depression and other psychological disorders (e.g. anxiety, panic). Nevertheless, only some of the patients experience a remission of their depressive symptoms. The occurrence of side effects and the only modest level of effectiveness result in inadequate compliance on the part of the patient. With venlafaxine and duloxetine two representatives of the selective serotonin and noradrenaline reuptake inhibitor (SSNRI) class of antidepressants are now available. SSNRIs have a dual effect coupled with high selectivity. The present article the extent to which this particular action mechanism results in an improved clinical efficacy and tolerability profile of the SSNRIs, in particular in comparison with SSRIs.

Antidepressive Agents↗
PubMed2005

Oxidative stress related markers in the "VITA" and the centenarian projects.

Oxidative stress seems to play an important role in the pathophysiology of Alzheimer's disease (AD). At present there are no easily accessible biochemical markers for AD. We performed activity assays for platelet MAO-B and erythrocyte Cu/Zn-SOD as well as Western blotting for these two proteins. Moreover, we assessed plasma lactoferrin and performed RFLP-analysis for the MAO-B-intron-13-polymorphism in patients from the Vienna-Transdanube Aging (VITA) and from the so called centenarian project. The first one, VITA, is a community-based cohort study of all 75 years old inhabitants of a geographical region of Vienna. The centenarian project investigates chronic care in-old patients suffering from AD. In both sexes platelet MAO-B activity increased significantly in the AD group, and Cu/Zn-SOD activity decreased, but the latter effect was significant only in females. No significant difference was found regarding plasma lactoferrin. No correlation was found between MAO-Bi13 and MAO-B platelet activity or allele MAO-Bi13 and disease frequency. These results point to the possibility that a combination of MAO-B and SOD activity levels might be useful tools for an early diagnosis of AD.

Aged↗
PubMed2004

Risperidone plasma levels, clinical response and side-effects.

INTRODUCTION: Assessment of the relation between oral risperidone dose, serum drug levels and clinical response may provide important information for rational treatment decisions. Inter-individual differences in the liver cytochrome P450 system, especially in the CYP2D6 subsystem, which account for a significant portion of risperidone metabolism, may also influence plasma drug levels and alter clinical response parameters. We thus prospectively investigated risperidone serum concentrations in relation to clinical efficacy and side-effects and genotyped major CYP2D6 polymorphisms to determine their effect upon these parameters. METHODS: Neuroleptic monotherapy with risperidone was administered to schizophrenia patients in a 6-week open dose clinical trial. Weekly assessments including CGI and PANSS ratings to assess psychopathology; SAS to assess medication side effects; and blood draws to quantify steady state plasma levels of risperidone and 9-OH-risperidone were carried out. In addition, major CYP2D6 polymorphisms including alleles *4, *6 and *14 were genotyped. RESULTS: Eighty-two patients were recruited. Mean oral dose of risperidone was 4.3 +/- 0.9 mg. Mean plasma level of both risperidone and 9-OH-risperidone together ("active moiety") was 41.6 +/- 26.6 ng/ml. Significant improvements in PANSS scales and the various subscales ensued. There was a positive linear correlation between active moiety plasma levels and dose (r = 0.291, p = 0.015) and between risperidone and 9-OH-risperidone levels (r = 0.262; p = 0.016). Nonresponders to pharmacotherapy (PANSS-Improvement < 30%) showed significantly higher active moiety plasma levels (49.9 +/- 30.7 ng/ml) than responders (38.2 +/- 17.0 ng/ml; p = 0.045) without significantly higher oral doses (p = 0.601). Patients with longer illness duration (> or = 3 years) had significantly higher plasma drug levels than those with a shorter course (< 3 years; p = 0.039). Extrapyramidal side effects (EPS) and plasma levels were not correlated (r = 0.028; p = 0.843), but higher plasma levels at week 2 predicted an incidence for EPS (p < 0.050). Accordingly, patients initially receiving higher oral doses of risperidone were significantly more likely to respond with EPS in the trial course. Eight patients (9.8%) were heterozygous carriers of the CYP2D6 allele *4. CYP2D6 polymorphisms did not predict clinical response, but predicted a tendential increase in the plasma risperidone to 9-OH-risperidone ratio (0.5 +/- 0.6 vs. 1.9 +/- 1.8; p = 0.120). DISCUSSION: The major finding was that responders to risperidone treatment had significantly lower blood levels of risperidone and 9-OH risperidone than patients who did not respond to the treatment despite administration of similar oral doses. The observed CYP2D6 polymorphisms did not contribute to altered clinical efficacy, but affected risperidone to 9-OH-risperidone ratios. Increased plasma levels of the active moiety in patients with longer illness may represent general aging effects. Conversely, the observed higher plasma levels in nonresponders may derive from unaccounted genetic metabolism abnormalities or Phase II metabolism disturbances. Patients initially receiving higher oral risperidone doses were more likely to respond with extrapyramidal side effects which reaffirms the need for careful titration. The high inter-individual variability in risperidone and 9-OH-risperidone metabolization and the relationship between clinical outcome and plasma levels warrants regular plasma level monitoring of both compounds to assess for the clinically relevant active moiety.

Adolescent↗
PubMed2004

[Diagnosis and treatment of panic disorder].

Panic disorder is defined as, recurrent, unexpected panic attacks. Panic attack means a period of intensive fear or discomfort, accompanied by a range of physical or psychological symptoms. Subsequently, anticipatory anxiety and avoidance behavior often develop. Panic disorder may or may not be accompanied by agoraphobia. Panic disorder can be treated both by psychotherapeutic and pharmacological measures. An ideal approach is combination therapy in the sense of a multimodal concept; with regard to cognitive behavioral therapy in particular, its effectiveness in the treatment of panic disorder is well documented. For pharmacotherapy, antidepressive agents, in particular selective serotonin reuptake inhibitors, are the drugs of first choice. Benzodiazepines should be given for only a few weeks until the antipanic effect of the antidepressants kicks in. With appropriate treatment, the prognosis is favorable.

Anti-Anxiety Agents↗
PubMed2004

[Schizophrenics in the doctor's office. Diagnostic and therapeutic aspects].

The diagnosis and treatment of schizophrenia is usually an interdisciplinary affair, with particular stress on cooperation between family doctor and psychiatrist. The practicing physician has a major role to play in the recognition of early schizophrenia. For reasons of time and the fact that further specialist diagnostic measures are mostly required, he will, as a rule, have to restrict himself to screening examinations. Patients with a positive screening outcome will be referred to a specialized early-recognition center or a specialist clinic for further diagnostic clarification. But the family doctor also has an important role in the treatment of these patients, e.g. when physical comorbidity presents, the patient rejects treatment by a psychiatrist, or has an early form of schizophrenia or a relapse. Today, medical treatment employs atypical neuroleptics, and treatment should be initiated as early as possible.

Antipsychotic Agents↗
PubMed2004

The neural basis of the P300 potential. Focus on the time-course of the underlying cortical generators.

The locations and time-courses of the neural generators of the event-related P300 potential have been well described using intracranial recordings. However, this invasive method is not adequate for usage in healthy volunteers or psychiatric patients and not all brain regions can be covered well with this approach. With functional MRI, a non-invasive method with high spatial resolution, most of these locations could be found again. However, the time-course of these activations can only be roughly determined with this method, even if an event-related fMRI design has been chosen. Therefore, we have now tried to analyse the time-course of the activations using EEG data providing a better time resolution. We have used Low Resolution Electromagnetic Tomography (LORETA) in the analysis of P300 data (27 electrodes) of healthy volunteers (n = 50) in the time frame 230-480 ms and found mainly the same activations that have been described using intracranial recordings or fMRI, i. e. the inferior parietal lobe/temporo-parietal junction (TPJ), the supplementary motor cortex (SMA) and the anterior cingulate cortex (ACC), the superior temporal gyrus (STG), the insula and the dorsolateral prefrontal cortex. In these selected regions, an analysis of the activation time-courses has been performed.

Acoustic Stimulation↗
PubMed2004

The septum pellucidum and its variants. An MRI study.

PURPOSE: Increased prevalence of cavum septi pellucidi (CSP) in schizophrenic patients in comparison to healthy subjects was reported previously. Our purpose was to evaluate the prevalence of variants of the septum pellucidum in healthy subjects in three different age groups. METHODS: 151 healthy subjects, including 46 children (age 6 +/- 4 years), 72 young adults (age 31 +/- 8 years) and 33 elderly adults (age 59 +/- 7 years) were examined with high-resolution MRI. Three observers analysed the images using a standardised protocol. We evaluated the incidences of CSP, cavum vergae (CV) and their length. RESULTS: CSP was detected in 80% of the cases in the paediatric group and 68% of young adults and in 72% of the elderly adults. A cavum vergae (CV) was noted in 22% of the children, in 39% of the young adults and in 36% of the elderly subjects. There was no significant difference between the age-related groups. CONCLUSION: We detected a high prevalence of cavum septi pellucidi without a significant age dependence. Enlarged cava septi pellucidi are rare in healthy subjects.

Adolescent↗
PubMed2004

Zotepine versus placebo in the treatment of schizophrenic patients with stable primary negative symptoms: a randomized double-blind multicenter trial.

BACKGROUND: In contrast to traditional antipsychotic medication, newer, the so called atypical antipsychotic drugs promise to reduce primary negative symptoms in both, acute and chronic schizophrenia and improve quality of life. Zotepine, a D (2)5HT (2A) antagonist, was compared to placebo in this clinical trial to address these issues. METHODS: In an adaptive, 8-week multicenter, double-blind, randomized, parallel group study, efficacy and tolerability as well as influence on quality of life of zotepine and placebo were compared in 80 schizophrenic patients (53 % males, age 41 +/- 11 years) who experienced stable primary negative symptoms. Efficacy was assessed using the PANSS (primary outcome criterion: PANSS negative score), CGI, and MADRS; safety was controlled by EPS (Simpson-Angus Scale), TDRS and adverse events. Quality of life was evaluated with the SF-36 health questionnaire. RESULTS: After eight weeks of treatment with an average dose of 131 +/- 49 mg/day of zotepine, no superior efficacy of zotepine compared to placebo with respect to the PANSS subscale "negative symptoms could be demonstrated. Although patients receiving zotepine showed a pronounced reduction (per protocol set: -7.8 +/- 5.8) during treatment, it was not statistically different from a marked placebo response (-6.5 +/- 5.8). Similar small but not significant differences between zotepine and placebo were found in other subscales of the PANSS, the CGI and the MADRS. With regards to the quality of life assessment, patients under zotepine showed better results in the physical component scale and psychological well-being scale. In general, zotepine was well tolerated and there was no excess of extrapyramidal symptoms compared to placebo. CONCLUSIONS: Zotepine was not superior to placebo in reducing the severity of stable primary negative symptoms in schizophrenic patients in this trial. The main reasons for this finding were a high placebo response in a selected population, a probably too low dose of zotepine, and a short study period. However, several findings show clinical benefit of zotepine therapy in efficacy and quality of life.

Adolescent↗
PubMed2004

Intravenous immunoglobulins containing antibodies against beta-amyloid for the treatment of Alzheimer's disease.

OBJECTIVE: Active or passive immunisation can mitigate plaque pathology in murine models of Alzheimer's disease (AD). Recently, it has been shown that antibodies against beta-amyloid (Abeta) are present in human immunoglobulin preparations (IVIgG), which specifically recognise and inhibit the neurotoxic effects of Abeta. This study reports the results from a pilot study using IVIgG in patients with AD. METHODS: Five patients with AD were enrolled and received monthly IVIgG over a 6 month period. Efficacy assessment included total Abeta/Abeta(1-42) measured in the CSF/serum as well as effects on cognition (ADAS-cog; CERAD) at baseline and at 6 months following IVIgG. RESULTS: Following IVIgG, total Abeta levels in the CSF decreased by 30.1% (17.3-43.5%) compared to baseline (p<0.05). Total Abeta increased in the serum by 233% (p<0.05). No significant change was found in Abeta(1-42) levels in the CSF/serum. Using ADAS-cog, an improvement of 3.7+/-2.9 points was detected. Scores in the MMSE were essentially unchanged (improved in four patients, stable in one patient) following IVIgG compared to baseline. CONCLUSION: Although the sample size of this pilot study is too small to draw a clear conclusion, the results of this pilot study provide evidence for a more detailed investigation of IVIgG for the treatment of AD.

Alzheimer Disease↗