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W Wolfgang Fleischhacker

Publications and source records attributed to W Wolfgang Fleischhacker.

At least 19 recordsLinked to original sources
PubMed2007

Neural substrates for episodic encoding and recognition of unfamiliar faces.

Functional MRI was used to investigate brain activation in healthy volunteers during encoding of unfamiliar faces as well as during correct recognition of newly learned faces (CR) compared to correct identification of distractor faces (CF), missed alarms (not recognizing previously presented faces, MA), and false alarms (incorrectly recognizing newly presented faces, FA). Encoding was associated with frontal, occipital/fusiform, thalamic, and cerebellar activation. CR produced activation in frontal and cerebellar regions, whereas CF activated frontal and occipitotemporal regions as well as the thalamus. In contrast, MA was associated with frontal and thalamic activation, and FA with frontal activation. The CR minus CF comparison showed left lateral prefrontal and parietal activation, while no suprathreshold positive signal changes were detected when subtracting the other conditions (CR minus MA, CR minus FA, and vice versa). These results support the view that the successful episodic retrieval of newly learned faces is based on a dorsal visual stream mechanism.

Adult↗
PubMed2006

Brain activation patterns during a selective attention test--a functional MRI study in healthy volunteers and unmedicated patients during an acute episode of schizophrenia.

In a previous functional magnetic resonance imaging (fMRI) study of high functioning outpatients with remitted schizophrenia, we found increased activity compared with healthy subjects across multiple areas of the brain, including the dorsolateral frontal cortex and the anterior cingulate, during a modified Stroop task. The same fMRI procedure was used in this subsequent study to investigate eight unmedicated patients during an acute episode of schizophrenia and eight healthy control subjects. Patients showed a reduced activation in dorsolateral prefrontal, anterior cingulate and parietal regions and a higher activation in temporal regions and posterior cingulate compared to healthy controls. Healthy controls showed a trend towards higher accuracy in the modified Stroop task compared to schizophrenia patients. Treatment with second generation antipsychotics may improve executive performance in patients with schizophrenia and facilitate a normalization of functional hypofrontality after symptomatic improvement.

Acute Disease↗
PubMed2006

The neural regions sustaining episodic encoding and recognition of objects.

In this functional MRI experiment, encoding of objects was associated with activation in left ventrolateral prefrontal/insular and right dorsolateral prefrontal and fusiform regions as well as in the left putamen. By contrast, correct recognition of previously learned objects (R judgments) produced activation in left superior frontal, bilateral inferior frontal, and right cerebellar regions, whereas correct rejection of distractor objects (N judgments) was associated with activation in bilateral prefrontal and anterior cingulate cortices, in right parietal and cerebellar regions, in the left putamen, and in the right caudate nucleus. The R minus N comparison showed activation in the left lateral prefrontal cortex and in bilateral cingulate cortices and precunei, while the N minus R comparison did not reveal any positive signal change. These results support the view that similar regions of the frontal lobe are involved in episodic encoding and retrieval processes, and that the successful episodic retrieval of newly learned objects is mainly based on a frontoparietal network.

Adult↗
PubMed2006

Alterations of glucose metabolism during treatment with clozapine or amisulpride: results from a prospective 16-week study.

Although second-generation antipsychotics have notable benefits as compared to typical antipsychotics, their use has been associated with metabolic disturbances, such as alterations of glucose homeostasis. It is still being debated whether this is a class effect of second-generation antipsychotics. We conducted a prospective, open study comparing body weight, parameters of insulin resistance in schizophrenia patients treated with either clozapine (n = 10) or amisuLpride ( n = 12). All parameters were assessed monthly over a period of 12 to 16 weeks. Body mass index (BMI), fasting serum insulin levels and the Homeostasis Model Assessment (HOMA) index for insulin resistance increased significantly in patients treated with clozapine. None of these parameters increased significantly in patients treated with amisulpride. This study indicates that treatment with clozapine appears to have a higher risk to lead to metabolic disturbances than amisupride.

Adolescent↗
PubMed2006

Sex differences in brain activation patterns during processing of positively and negatively valenced emotional words.

BACKGROUND: Previous studies have suggested that men and women process emotional stimuli differently. In this study, we used event-related functional magnetic resonance imaging (fMRI) to investigate gender differences in regional cerebral activity during the perception of positive or negative emotions. METHOD: The experiment comprised two emotional conditions (positively/negatively valenced words) during which fMRI data were acquired. RESULTS: Thirty-eight healthy volunteers (19 males, 19 females) were investigated. A direct comparison of brain activation between men and women revealed differential activation in the right putamen, the right superior temporal gyrus, and the left supramarginal gyrus during processing of positively valenced words versus non-words for women versus men. By contrast, during processing of negatively valenced words versus non-words, relatively greater activation was seen in the left perirhinal cortex and hippocampus for women versus men, and in the right supramarginal gyrus for men versus women. CONCLUSIONS: Our findings suggest gender-related neural responses to emotional stimuli and could contribute to the understanding of mechanisms underlying the gender disparity of neuropsychiatric diseases such as mood disorders.

Adult↗
PubMed2006

Gender differences in regional cerebral activity during the perception of emotion: a functional MRI study.

Whether men activate different brain regions during various emotions compared to women or whether gender differences exist in transient emotional states has been the subject of only few studies. We used event-related functional magnetic resonance imaging (fMRI) to investigate gender differences during the perception of positive or negative emotions. The experiment comprised two emotional conditions (pleasant/unpleasant visual stimuli) during which fMRI data were acquired. Altogether, 38 healthy volunteers (19 males, 19 females) were investigated. When subtracting the activation values of men from those of women, suprathreshold positive signal changes were detected in the right posterior cingulate, the left putamen and the left cerebellum during positive mood induction, and in bilateral superior temporal gyri and cerebellar vermis during negative mood induction. The subtraction of activation values of women from those of men yielded no significant differences. Our findings suggest gender-related neural responses to emotional stimuli and could contribute to the understanding of mechanisms underlying gender-related vulnerability of the prevalence and severity of neuropsychiatric disorders.

Adult↗
PubMed2006

Language lateralization in unmedicated patients during an acute episode of schizophrenia: a functional MRI study.

In a previous fMRI study of high-functioning outpatients with remitted schizophrenia, we found that healthy subjects and schizophrenia patients showed similar patterns of activation during a verbal fluency task. However, the activation in controls was primarily in Broca's area on the left, while it was more bilateral for schizophrenia patients, implicating a reduced language lateralization in schizophrenia patients. The same fMRI procedure was used in this subsequent study to investigate unmedicated patients during an acute episode of schizophrenia. Schizophrenia patients showed reduced language lateralization in the frontal cortex, because of a more bilateral activation of Broca's area compared with a primarily left hemisphere activation in healthy controls. Furthermore decreased lateralization was correlated to the severity of hallucinations. Although patients with schizophrenia showed a significantly reduced performance on the verbal fluency task when compared with healthy subjects, we were not able to find evidence of decreased language-related activity in the left hemisphere. These results suggest that decreased language lateralization is also evident in unmedicated patients experiencing an acute episode of schizophrenia.

Acute Disease↗
PubMed2006

[Antipsychotic drug-induced changes in metabolism].

Antipsychotic medications are a mainstay in the treatment of schizophrenia and are widely used in other psychiatric conditions. New generation antipsychotic agents (NGAs) are increasingly replacing first generation antipsychotic agents (FGAs), mainly due to a decreased risk for extrapyramidal symptoms, better overall tolerability, as well as some efficacy advantages. However, some of these NGAs are associated with adverse metabolic effects such as substantial weight gain, the induction of insulin resistance and lipid disorders. Among these substances, clozapine and olanzapine induce the most significant weight gain, olanzapine mainly by increasing body fat and both of these antipsychotics have been associated with disturbances in glucose metabolism. Diabetes mellitus induced by treatment with some NGAs occurred in many cases within days to weeks after initiation of SGA therapy, in some cases hyperglycemia promptly resolved after discontinuation of the medication and several reports have documented recurrent hyperglycemia after a rechallenge with the same drug. One possible pathomechanism for hyperglycemia induced by these NGAs is the induction of insulin resistance via humoral and/or cellular pathways. Alternatively, NGA induced diabetes may occur because of weight gain or a change in body fat distribution with a shift to a predominantly visceral fat type or through a direct effect on insulin sensitive target tissues. In this article we like to review the metabolic side effects of NGA treatment, highlight recent advances in the pathogenesis of these metabolic complications and discuss potential treatments of these side effects.

Antipsychotic Agents↗
PubMed2006

Association between antipsychotic-induced elevation of liver enzymes and weight gain: a prospective study.

We conducted a prospective, open study in schizophrenia patients treated with second-generation antipsychotics in order to investigate the risk for elevation of liver enzymes and its correlation to antipsychotic-induced weight gain. Body mass index, serum transaminases, plasma serum levels of the antipsychotic used, and blood cell counts were measured weekly during the first 6 weeks of treatment and monthly thereafter. A considerable proportion of subjects showed an increase beyond normal levels of at least one of the measured transaminases. In all but one case, the elevation of liver enzymes was transient. We found a statistically significant correlation between weight gain and liver enzyme elevation. The group of patients that had gained at least 7% of the baseline body weight showed significantly higher increases of transaminases as compared with those who had gained less than 7% weight. We conclude that antipsychotic-induced elevation of liver enzymes is mostly transient and could be associated with weight gain.

Adolescent↗
PubMed2006

Treatment of schizophrenia patients: comparing new-generation antipsychotics to each other.

PURPOSE OF REVIEW: Although the debate on whether new antipsychotics have advantages over the old neuroleptics has recently been refueled by the first publication of the Clinical Antipsychotic Trials of Intervention Effectiveness results, one of the new challenges in the pharmacological management of schizophrenia patients is to choose among the new-generation drugs. RECENT FINDINGS: Earlier work has compared these medications primarily to traditional antipsychotics and until very recently there was little published information on the relative efficacy/safety of new-generation antipsychotics. SUMMARY: This review covers studies wherein therapeutic effects and adverse events of these drugs in schizophrenia patients were compared in head-to-head studies and that were published in 2005. Information is clearly more homogenous on the safety profile side, while the available evidence still offers little help for the clinicians' daily struggles to find the optimally effective antipsychotic for an individual schizophrenia patient.

Antipsychotic Agents↗
PubMed2006

Early changes of plasma lipids during treatment with atypical antipsychotics.

Metabolic side effects have been found earlier during treatment with second-generation antipsychotics. Among those disturbances serum lipids are less investigated. We conducted a prospective, open study in schizophrenia patients in order to compare body weight and serum lipids during treatment with amisulpride, ziprasidone, clozapine or olanzapine over a period of 4 weeks. Body mass index, total cholesterol and triglycerides increased in patients treated with clozapine and olanzapine whereas high-density lipoprotein cholesterol decreased in those patients. In patients treated with amisulpride or ziprasidone, we found a decrease in body mass index and total cholesterol whereas high-density lipoprotein cholesterol increased. Our results indicate that treatment with ziprasidone and amisulpride is more favourable than treatment with clozapine and olanzapine with respect to the risk to induce weight gain and hyperlipidaemia. These results are important with regard to the increased risk for cardiovascular complications in patients with schizophrenia.

Adolescent↗
PubMed2006

Executive function and memory in relation to olfactory deficits in alcohol-dependent patients.

BACKGROUND: Prior research indicates that chronic alcoholism is accompanied by olfactory deficits. These have been suggested to reflect dysfunctions in olfactory brain regions. The present study investigated the role of neurocognitive functioning in tests (executive function and memory) sensitive to the functional integrity of brain areas that are crucial to olfactory processing in patients with alcohol dependence. METHODS: Performance on olfactory functions (detection threshold, quality discrimination, identification), executive function (Wisconsin Card Sorting Test), and memory (German version of the California Verbal Learning Test) was assessed in 32 alcohol-dependent patients and 30 healthy comparison subjects, comparable in age, gender, and smoking status. RESULTS: Compared with controls, alcohol-dependent patients were impaired in all 3 domains, olfactory functions, executive function, and memory. In patients, olfactory discrimination ability was positively correlated with executive function performance. Regression analyses conducted to clarify the relation between group (patients vs controls), executive function, memory, and olfactory functions indicated that group was the only significant predictor of olfactory detection threshold and identification, and both group and executive function were found to be the significant predictors of olfactory discrimination. CONCLUSIONS: Olfactory deficits in alcohol dependence appear to be associated with prefrontal cognitive dysfunction. Results indicate that olfactory quality discrimination deficits are related to executive function impairment. These findings add to the available research on frontal lobe dysfunction in alcoholism, suggesting that alcohol-related olfactory discrimination deficits may be associated with impairment in the functional integrity of the prefrontal lobe.

Adult↗
PubMed2005

Correlates of subjective and functional outcomes in outpatient clinic attendees with schizophrenia and schizoaffective disorder.

Outcome in schizophrenia is multidimensional and, thus, consists of clinical,humanitarian, rehabilitative and cost domains. Accordingly, recovery is conceptualized as the ability to function in the community, socially and vocationally, as well as being relatively free of disease-related psychopathology. The present cross-sectional study examined the relationship of premorbid functioning, psychopathology, insight, attitudes toward medication and side-effects, as well as sociodemographic factors with treatment outcomes in terms of quality of life (QOL) and psychosocial functioning among 60 regular attendees of a specialized schizophrenia outpatient clinic. Both insight into the illness as well as attitudes toward treatment indicated satisfactory compliance. Premorbid school and social functioning were positively correlated with actual employment status, and premorbid social functioning was further positively correlated with QOL and global functioning. Attitudes toward treatment were positively associated with global QOL, and with the patients' living situation. Both positive and negative symptoms as well as asthenia were negatively associated with QOL, while cognitive symptoms negatively influenced occupational functioning. Older patients lived independently and/or in a partnership more often, but had a lesser likelihood of competitive employment. Our observations suggest that subjective and functional outcomes in highly compliant patients are mainly predicted by psychopathological symptoms and unchangeable sociodemographic variables.

Activities of Daily Living↗
PubMed2005

Longitudinal volumetric MRI study in first- and multiple-episode male schizophrenia patients.

In this longitudinal study we compared brain volume changes in first- and multiple-episode patients with schizophrenia to normal aging changes observed in healthy control subjects scanned at comparable times. Two to four years after an initial examination including MRI volumetry, we followed up 21 first episode patients, 17 patients after multiple episodes of schizophrenia, and 20 healthy controls. Volumetric measurements of left and right hemispheres, total brain volume, lateral ventricles, hippocampus and amygdala as well as a clinical evaluation were performed. Patients with schizophrenia showed significant ventricular enlargement and volume reduction of the hippocampus-amygdala complex compared with healthy control subjects both at baseline and follow-up. While there were no differences between patients and controls with respect to mean annual volume changes in the measured regions, patients with schizophrenia showed higher between-subject variability in ventricular volume change. These data are consistent with cross-sectional studies demonstrating ventricular enlargement and hippocampal volume deficits in schizophrenia. However, we were not able to demonstrate a difference in the rate of volume changes over time that distinguished patients with schizophrenia from healthy controls for any of the brain structures measured. Drawbacks of the study are that the follow-up was done after a relatively short interval and that there was a difference in time to follow-up and age between patients and controls. Our results do not support the hypothesis that schizophrenia leads to progressive volume reduction in these areas, although there may be a subset of patients with morphologically visible disease progression.

Adult↗
PubMed2005

The European First Episode Schizophrenia Trial (EUFEST): rationale and design of the trial.

BACKGROUND: Most studies comparing second generation antipsychotics with classical neuroleptics have been conducted in more or less chronic schizophrenia patients. Such studies were usually conducted in highly selected samples, and were generally designed and financed by the manufacturer of the drug tested. These and other facts have stimulated discussions regarding the effectiveness of the new generation of antipsychotics. AIMS: The aim of the European First Episode Schizophrenia Trial (EUFEST) is to compare treatment with amisulpride, quetiapine, olanzapine and ziprasidone to a low dose of haloperidol in an unselected sample of first episode schizophrenia patients with minimal prior exposure to antipsychotics. METHODS: 500 patients between the ages of 18-40 meeting DSM-IV criteria for schizophrenia, schizoaffective disorder or schizophreniform disorder are randomly allocated to one year of treatment with one of the drugs under study. The primary outcome measure is retention in treatment, defined as time to discontinuation of study drug. Loss of retention can be the result of insufficient clinical effect, or lack of tolerability or acceptance. Secondary measures include changes in different dimensions of psychopathology, side effects, compliance, social needs, quality of life, substance abuse and cognitive functions. CONCLUSIONS: At present, more than 400 patients have been recruited and randomized in the following countries: Austria, Belgium, Bulgaria, Czech Republic, Germany, France, Israel, Italy, the Netherlands, Poland, Rumania, Spain, Sweden and Switzerland: The study should be finished by the end of 2006 and it is expected that results will yield relevant clinical information with regard to the effectiveness of the second generation antipsychotics. This effort represents the first independently designed trans-European schizophrenia treatment trial.

Adolescent↗
PubMed2005

Comparative efficacy of antipsychotics in the treatment of schizophrenia: a critical assessment.

Because of their broader spectrum of efficacy and lower risk of short- and long-term motor side-effects in comparison to first generation 'typical' antipsychotics (FGAs), second generation 'atypical' antipsychotics (SGAs) are rapidly becoming the standard of antipsychotic pharmacotherapy. It is unclear, however, as to how different SGAs compare in efficacy since the multitude of studies and integrative reviews seemingly provide discrepant information in this regard. To address this issue, we critically review three distinct approaches to analysis of data from randomized controlled clinical trials of the efficacy of SGAs in the treatment of schizophrenia and schizoaffective disorder: (i) comparing average improvement in symptomatology with different SGAs; (ii) comparing average improvement observed with different SGAs relative to haloperidol; and (iii) head-head trials comparing one SGA to another. We discuss the strengths and limitations of each approach with reference to the reports in which it was applied to assess comparative antipsychotic efficacy. We conclude that the most informative picture is obtained by using each of these strategies, looking at all available data, and then putting all the results together. Data thus far do not support claims of differential efficacy among SGAs with the singular exception of clozapine possibly still being the gold standard of antipsychotic efficacy in otherwise treatment-refractory schizophrenia. Dosing appears to be a critical variable in optimizing efficacy.

Antipsychotic Agents↗