In non-human mammals, the neuropeptide oxytocin is a key mediator of complex emotional and social behaviors, including attachment, social recognition, and aggression. Oxytocin reduces anxiety and impacts on fear conditioning and extinction. Recently, oxytocin administration in humans was shown to increase trust, suggesting involvement of the amygdala, a central component of the neurocircuitry of fear and social cognition that has been linked to trust and highly expresses oxytocin receptors in many mammals. However, no human data on the effects of this peptide on brain function were available. Here, we show that human amygdala function is strongly modulated by oxytocin. We used functional magnetic resonance imaging to image amygdala activation by fear-inducing visual stimuli in 15 healthy males after double-blind crossover intranasal application of placebo or oxytocin. Compared with placebo, oxytocin potently reduced activation of the amygdala and reduced coupling of the amygdala to brainstem regions implicated in autonomic and behavioral manifestations of fear. Our results indicate a neural mechanism for the effects of oxytocin in social cognition in the human brain and provide a methodology and rationale for exploring therapeutic strategies in disorders in which abnormal amygdala function has been implicated, such as social phobia or autism.
Clinical interest in the so-called atypical antipsychotics currently focuses on the possibility of improving the negative symptoms of schizophrenia and the cognitive dysfunction associated with the disease. While clozapine has been shown to be effective in this respect, no data are available on zotepine. We report on a double-blind randomized study designed to evaluate the impact of zotepine and clozapine on cognitive dysfunction in schizophrenia. Cognitive function was operationalized by a maze test in which patients traversed computer-displayed mazes of increasing complexity. Passage time, route, and motor errors were evaluated. 25 schizophrenic (DSM-IIIR) patients were included in each group. After washout, they were randomized on zotepine or clozapine and given up to 450 mg of substance each. Patients were followed for six weeks and evaluated weekly. We report on a subsample of 26 patients matched for baseline BPRS, SANS, and age. 13 matched healthy persons were recruited as controls. ANOVA with group and course over time as factors was used for analysis. Both clozapine and zotepine achieved a highly significant decrease in overall symptoms (BPRS) and negative symptoms (SANS). Zotepine and clozapine were equally effective. In the maze tests, motor errors in simple mazes were stable over time and differentiated schizophrenics from controls as a "trait" marker. In passage time and maze route, schizophrenics performed worse than controls. An improvement by medication was evident in both medication groups, but was more pronounced in the zotepine-treated group. The study confirms previous results on the efficacy of clozapine and zotepine in treating negative symptoms of schizophrenia. The data presented show for the first time that zotepine is efficacious in improving cognitive dysfunction, confirming this substance's value as an atypical antipsychotic.
In Germany, clomethiazole (CLO) and benzodiazepines are predominantly used as therapeutic agents in the treatment of the alcohol withdrawal syndrome (AWS). These agents have disadvantages such as sedation, risk of respiratory insufficiency, and cardiovascular complications as well as addictive potential. Alternatively, it could be demonstrated that both tiapride (TIA) and carbamazepine (CBZ) are efficient in the treatment of AWS with less toxicity. However, they seem to be less effective in AWS than CLO as single agents. But no systematic comparison of the combination of TIA and CBZ against an established therapeutic standard can be found in the literature. Therefore, we compared the combination of TIA and CBZ with CLO in two open exploratory studies with matched samples. Outcome parameters were heart rate, blood pressure, complications, withdrawal symptoms (CIWA-Ar scale), and general clinical state (CGI scale). A retrospective evaluation of medical records (30 TIA+CBZ, 30 CLO) was followed by an open prospective study (40 TIA+CBZ, 40 CLO). Both studies revealed similar efficacy in terms of psychopathologic and vegetative symptoms. Vegetative recovery seems to be faster with TIA+CBZ. Results of this exploratory study have to be confirmed by a controlled double-blind study with severity of AWS as an experimental factor.
Deficits in social functioning are a core symptom of schizophrenia and an important criterion for evaluating the success of treatment. However, there is little agreement regarding its measurement. A common, often cited instrument for assessing self-reported social functioning is the Social Functioning Scale (SFS). The study aimed to investigate the reliability and validity of the German translation. 101 patients suffering from schizophrenia (SZ) and 101 matched controls (C) (60 male / 41 female, 35.8 years in both groups) completed the German version. In addition, demographic, clinical, and functional data were collected. Internal consistency was investigated calculating Cronbach’s alpha for SFS full scale (α: .81) and all subscales (α: .59-.88). Significant bivariate correlation coefficients were found between all subscales as well as between all subscales and full scale (p <.01). For the total sample, principal component analysis gave evidence to prefer a single-factor solution (eigenvalue ≥ 1) accounting for 48.5 % of the variance. For the subsamples, a two-component solution (SZ; 57.0 %) and a three-component solution (C; 65.6 %) fitted best, respectively. For SZ and C, significant associations were found between SFS and external criteria. The main factor “group” emerged as being significant. C showed higher values on both subscales and full scale. The sensitivity of the SFS was examined using discriminant analysis. 86.5% of the participants could be categorized correctly to their actual group. The German translation of the SFS turned out to be a reliable and valid questionnaire comparable to the original English version. This is in line with Spanish and Norwegian translations of the SFS. Concluding, the German version of the SFS is well suited to become a useful and practicable instrument for the assessment of social functioning in both clinical practice and research. It accomplishes commonly used external assessment scales.
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