Maria A. Rettenbacher

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.

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.

Effects of six second generation antipsychotics on body weight and metabolism - risk assessment and results from a prospective study.

BACKGROUND Due to the association of second generation antipsychotics (SGAs) with weight gain and alterations of glucose and lipid homeostasis, we aimed to group six commonly prescribed SGAs into classes of differing risks. METHODS Twenty-eight patients meeting the criteria for a diagnosis of schizophrenic disorder according to ICD-10 were assigned to monotherapy with olanzapine, clozapine, quetiapine, amisulpride, ziprasidone or risperidone. The levels of glucose and lipid metabolism were assessed before and after 28 days of treatment. RESULTS Based on cluster analysis, olanzapine and clozapine were found to constitute a high-risk group for metabolic dysregulation while amisulpride, quetiapine, risperidone and ziprasidone could be assigned to a non-high-risk group. Subjects from the high-risk group displayed significant weight gain with concomitant increases of HOMA-IR, levels of insulin, total cholesterol, TG, LDL-C and leptin. No significant changes were observed in the non-high-risk group. CONCLUSION The results of this study support the conclusion of the Consensus Development Conference on Antipsychotic Drugs and Obesity and Diabetes that certain SGAs are associated with a higher risk for weight gain, insulin resistance and dyslipidemia.

Cognitive impairment in schizophrenia: Clinical ratings are not a suitable alternative to neuropsychological testing

Despite the fact that cognitive impairment rated with clinical rating scales has been shown to be a poor proxy for cognitive functioning measured with a performance-based assessment battery, studies are still using this approach to predict aspects of outcome in schizophrenia. In the current study 106 outpatients with chronic schizophrenia who had been stable both from a symptomatic and a medication perspective for a period of 6 months before study inclusion were investigated to assess the relationship between a clinical rating of cognitive impairment and the actual performance on neuropsychological tests. The cognitive component of the PANSS was compared to results from a neuropsychological test battery which was selected to cover domains known to be impaired in patients with schizophrenia. Correlations of the cognitive component of the PANSS with the individual neuropsychological tests were low. They ranged between 0.19 and 0.35. None of them was sufficiently high to indicate that the cognitive component of the PANSS adequately covers the cognitive dimension measured by the respective neuropsychological test. These data clearly show that clinical assessment of cognitive deficits by the PANSS is not a viable alternative to neuropsychological testing to obtain information about cognitive functioning in schizophrenia.

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.

Neutropenia Induced by Second Generation Antipsychotics: A Prospective Investigation

BACKGROUND Clozapine is known to induce neutropenia as well as agranulocytosis. Some cases of olanzapine- and risperidone-induced neutropenia and agranulocytosis have also been reported. We prospectively investigated schizophrenia patients treated with second generation antipsychotics with respect to alterations of white blood cell counts. METHODS In an analysis of our drug monitoring program, we studied white blood cell counts in 104 patients receiving different second generation antipsychotics other than clozapine for at least six months and compared them with those of 28 patients receiving clozapine. RESULTS We found neutropenia (neutrophils <2 000/microL) in the mixed group in 17.6% and in 11.8% of patients treated with clozapine during the first 6 months. There was no statistically significant difference between those groups with respect to the risk to develop neutropenia during the investigation period. There was no case of agranulocytosis. Neutropenia was transient in all patients. Eosinophilia occurred in some patients that developed neutropenia later on but had no significant predictive value.

QTc variability in schizophrenia patients treated with antipsychotics and healthy controls

Abstract: QTc prolongation is associated with the administration of some antipsychotics but the QTc interval is also known to vary physiologically. There is little published evidence about changes in QTc variability during treatment with antipsychotics. In this prospective investigation, we analyzed ECGs in 61 patients suffering from a schizophrenic disorder who were treated with different antipsychotics and 31 sex- and age-matched healthy controls. We found no differences in QTc intervals nor in QTc variability between patients and controls. Our results raise the question of the clinical relevance of a single ECG for diagnostics of cardiac complications in schizophrenia patients and suggest the need to conduct ECG monitoring in patients at high risk for cardiac complications during antipsychotic treatment.

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.

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.

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

Abstract: 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.